Comparative Efficacy of Autologous Stromal Vascular Fraction and Autologous Adipose-Derived Mesenchymal Stem Cells Combined With Hyaluronic Acid for the Treatment of Sheep Osteoarthritis.

PubMed

Lv, Xiaoteng; He, Jiyin; Zhang, Xue; Luo, Xuan; He, Na; Sun, Zhongwei; Xia, Huitang; Liu, Victor; Zhang, Li; Lin, Xiangming; Lin, Liping; Yin, Huabin; Jiang, Dong; Cao, Wei; Wang, Richard; Zhou, Guangdong; Wang, Wen

2018-01-01

The current study explored whether intra-articular (IA) injection of autologous adipose mesenchymal stem cells (ASCs) combined with hyaluronic acid (HA) achieved better therapeutic efficacy than autologous stromal vascular fraction (SVF) combined with HA to prevent osteoarthritis (OA) progression and determined how long autologous ASCs combined with HA must remain in the joint to observe efficacy. OA models were established by performing anterior cruciate ligament transection (ACLT) and medial meniscectomy (MM). Autologous SVF (1×10 7 mononuclear cells), autologous low-dose ASCs (1×10 7 ), and autologous high-dose ASCs (5×10 7 ) combined with HA, and HA alone, or saline alone were injected into the OA model animals at 12 and 15 weeks after surgery, respectively. Compared with SVF+HA treatment, low-dose ASC+HA treatment yielded better magnetic resonance imaging (MRI) scores and macroscopic results, while the cartilage thickness of the tibial plateau did not differ between low, high ASC+HA and SVF+HA treatments detected by micro-computed tomography (µCT). Immunohistochemistry revealed that high-dose ASC+HA treatment rescued hypertrophic chondrocytes expressing collagen X in the deep area of articular cartilage. Western blotting analysis indicated the high- and low-dose ASC+HA groups expressed more collagen X than did the SVF+HA group. Enzyme-linked immunosorbent assay showed treatment with both ASC+HA and SVF+HA resulted in differing anti-inflammatory and trophic effects. Moreover, superparamagnetic iron oxide particle (SPIO)-labeled autologous ASC signals were detected by MRI at 2 and 18 weeks post-injection and were found in the lateral meniscus at 2 weeks and in the marrow cavity of the femoral condyle at 18 weeks post-injection. Thus, IA injection of autologous ASC+HA may demonstrate better efficacy than autologous SVF+HA in blocking OA progression and promoting cartilage regeneration, and autologous ASCs (5×10 7 cells) combined with HA potentially survive

Changes in leucocyte migration after renal transplantation

PubMed Central

Smith, M. G. M.; Eddleston, A. L. W. F.; Dominguez, J. A.; Evans, D. B.; Bewick, M.; Williams, Roger

1969-01-01

The leucocyte migration test, an in-vitro measure of cellular immunity, has been used to follow the changes in cell-mediated hypersensitivity to kidney and histocompatibility antigens in three patients after renal transplantation. Inhibition of leucocyte migration, indicating strong sensitization to the antigens used, occurred in each patient, starting five to seven days after transplantation. Satisfactory renal function had not been established in any of the patients at this time. In one case inhibition of leucocyte migration persisted almost continuously until the 24th day and was associated with poor renal function proved histologically to be due to rejection. Treatment with increased dosage of prednisone was associated with a rapid reversion to normal of the migration index and improvement in renal function. Later, inhibition of migration occurred again, and shortly afterwards the graft ceased to function. In the other two cases the migration index became normal without alteration in immunosuppressive therapy and a satisfactory diuresis followed. It is suggested that this simple test should prove useful in the specific diagnosis of rejection and in control of immunosuppressive therapy. ImagesFig. 3Fig. 4 PMID:4899455

Leucocyte count in young adults with first-ever ischaemic stroke: associated factors and association on prognosis.

PubMed

Heikinheimo, Terttu; Putaala, Jukka; Haapaniemi, Elena; Kaste, Markku; Tatlisumak, Turgut

2015-02-01

Limited data exist on the associated factors and correlation of leucocyte count to outcome in young adults with first-ever ischaemic stroke. Our objectives were to investigate factors associated with elevated leucocyte count and whether there is correlation between leucocyte count and short- and long-term outcomes. Of our database of 1008 consecutive patients aged 15 to 49, we included those with leucocyte count measured within the first two days from stroke onset. Outcomes were three-month and long-term disability, death, and vascular events. Linear regression was used to explore baseline variables associated with leucocyte count. Logistic regression and Cox proportional models studied the association between leucocyte count and clinical outcomes. In our study cohort of 781 patients (61.7% males; mean age 41.4 years), mean leucocyte count was high: 8.8 ± 3.1 × 10(9) cells/L (Reference range: 3.4-8.2 × 10(9) cells/L). Higher leucocyte levels were associated with dyslipidaemia, smoking, peripheral arterial disease, stroke severity, and lesion size. After adjustment for age, gender, relevant risk factors, both continuous leucocyte count and the highest quartile of leucocyte count were independently associated with unfavourable three-month outcome. Regarding events in the long-term (follow-up 8.1 ± 4.2 years in survivors), no association between leucocyte count and the event risks appeared. Among young stroke patients, high leucocyte count was a common finding. It was associated with vascular disease and its risk factors as well as severity of stroke, but it was also independently associated with unfavourable three-month outcome in these patients. There was no association with the long-term outcome. [Correction added on 31 October 2013 after first online publication: In the Results section of the Abstract, the cohort of 797 patients in this study was corrected to 781 patients.]. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Mind the cell: Seasonal variation in telomere length mirrors changes in leucocyte profile.

PubMed

Beaulieu, Michaël; Benoit, Laure; Abaga, Steven; Kappeler, Peter M; Charpentier, Marie J E

2017-10-01

Leucocytes are typically considered as a whole in studies examining telomere dynamics in mammals. Such an approach may be precarious, as leucocytes represent the only nucleated blood cells in mammals, their composition varies temporally, and telomere length differs between leucocyte types. To highlight this limitation, we examined here whether seasonal variation in leucocyte composition was related to variation in telomere length in free-ranging mandrills (Mandrilllus sphinx). We found that the leucocyte profile of mandrills varied seasonally, with lower lymphocyte proportion being observed during the long dry season presumably because of the combined effects of high nematode infection and stress at that time of the year. Interestingly, this low lymphocyte proportion during the long dry season was associated with shorter telomeres. Accordingly, based on longitudinal data, we found that seasonal changes in lymphocyte proportion were reflected by corresponding seasonal variation in telomere length. Overall, these results suggest that variation in lymphocyte proportion in blood can significantly affect telomere measurements in mammals. However, lymphocyte proportion did not entirely explain variation in telomere length. For instance, a lower lymphocyte proportion with age could not fully explain shorter telomeres in older individuals. Overall, our results show that telomere length and leucocyte profile are strongly although imperfectly intertwined, which may obscure the relationship between telomere dynamics and ageing processes in mammals. © 2017 John Wiley & Sons Ltd.

A novel point mutation in CD18 causing the expression of dysfunctional CD11/CD18 leucocyte integrins in a patient with leucocyte adhesion deficiency (LAD)

PubMed Central

Mathew, E C; Shaw, J M; Bonilla, F A; Law, S K A; Wright, D A

2000-01-01

Leucocyte adhesion deficiency type 1 (LAD-1) is characterized by the incapacity of leucocytes to carry out their adhesion functions via their CD11/CD18 antigens, which are also referred to as the leucocyte integrins. The patients generally suffer from poor wound healing and recurrent bacterial and fungal infections. In severe cases, the infections are often systemic and life-threatening. A LAD patient (AW) of moderate phenotype has been identified but, unlike most other cases, the level of CD11/CD18 antigens on her leucocytes are uncharacteristically high for a LAD patient. Molecular analysis revealed that she is a compound heterozygote for CD18 mutations. She has inherited a D231H mutation from her father and a G284S mutation from her mother. By transfection studies, it was established that the G284S mutation does not support CD11/CD18 antigen expression on the cell surface. In contrast, the D231H mutation does not affect CD18 forming integrin heterodimers with the CD11 antigens on the cell surface. However, the expressed integrins with the D231H mutation are not adhesive to ligands. PMID:10886250

Comparison of Effects of Running and Playing Exercises on Differential Leucocyte Count in Young Elite Athletes

ERIC Educational Resources Information Center

Cenikli, Abdullah

2016-01-01

The aims of the present research are to test the effects of running and playing exercises on leucocyte and differential leucocyte accounts, and to test the possible differences between running and playing exercises in terms of leucocyte accounts. They were thirty two male young soccer players. Participants arrived at the laboratory after a 12-hour…

Transplantation of autologous bone marrow-derived mesenchymal stem cells for traumatic brain injury☆

PubMed Central

Jiang, Jindou; Bu, Xingyao; Liu, Meng; Cheng, Peixun

2012-01-01

Results from the present study demonstrated that transplantation of autologous bone marrow-derived mesenchymal stem cells into the lesion site in rat brain significantly ameliorated brain tissue pathological changes and brain edema, attenuated glial cell proliferation, and increased brain-derived neurotrophic factor expression. In addition, the number of cells double-labeled for 5-bromodeoxyuridine/glial fibrillary acidic protein and cells expressing nestin increased. Finally, blood vessels were newly generated, and the rats exhibited improved motor and cognitive functions. These results suggested that transplantation of autologous bone marrow-derived mesenchymal stem cells promoted brain remodeling and improved neurological functions following traumatic brain injury. PMID:25806058

Chimeric Human Skin Substitute Tissue: A Novel Treatment Option for the Delivery of Autologous Keratinocytes.

PubMed

Rasmussen, Cathy A; Allen-Hoffmann, B Lynn

2012-04-01

For patients suffering from catastrophic burns, few treatment options are available. Chimeric coculture of patient-derived autologous cells with a "carrier" cell source of allogeneic keratinocytes has been proposed as a means to address the complex clinical problem of severe skin loss. Currently, autologous keratinocytes are harvested, cultured, and expanded to form graftable epidermal sheets. However, epidermal sheets are thin, are extremely fragile, and do not possess barrier function, which only develops as skin stratifies and matures. Grafting is typically delayed for up to 4 weeks to propagate a sufficient quantity of the patient's cells for application to wound sites. Fully stratified chimeric bioengineered skin substitutes could not only provide immediate wound coverage and restore barrier function, but would simultaneously deliver autologous keratinocytes to wounds. The ideal allogeneic cell source for this application would be an abundant supply of clinically evaluated, nontumorigenic, pathogen-free, human keratinocytes. To evaluate this potential cell-based therapy, mixed populations of a green fluorescent protein-labeled neonatal human keratinocyte cell line (NIKS) and unlabeled primary keratinocytes were used to model the allogeneic and autologous components of chimeric monolayer and organotypic cultures. Relatively few autologous keratinocytes may be required to produce fully stratified chimeric skin substitute tissue substantially composed of autologous keratinocyte-derived regions. The need for few autologous cells interspersed within an allogeneic "carrier" cell population may decrease cell expansion time, reducing the time to patient application. This study provides proof of concept for utilizing NIKS keratinocytes as the allogeneic carrier for the generation of bioengineered chimeric skin substitute tissues capable of providing immediate wound coverage while simultaneously supplying autologous human cells for tissue regeneration.

The impact of cryopreservation on human peripheral blood leucocyte bioenergetics.

PubMed

Keane, Kevin N; Calton, Emily K; Cruzat, Vinicius F; Soares, Mario J; Newsholme, Philip

2015-05-01

Circulating immune cells are considered a source for biomarkers in health and disease, since they are exposed to nutritional, metabolic and immunological stimuli in the vasculature. Cryopreservation of leucocytes is routinely used for long-term storage and determination of phenotypic/functional changes at a later date. Exploring the role of bioenergetics and mitochondrial (dys)function in leucocytes is often examined by using freshly isolated cells. The aim of the pilot study described herein was to assess leucocyte bioenergetics in cryopreserved cells. Leucocytes were isolated from whole blood, counted and frozen in liquid nitrogen (LN2) for a period of 3 months. Cells were thawed at regular intervals and bioenergetic analysis performed using the Seahorse XFe96 flux analyser. Cryogenic storage reduced cell viability by 20%, but cell bioenergetic responses were largely intact for up to 1 month storage in LN2. However, after 1 month storage, mitochondrial function was impaired as reflected by decreasing basal respiration, ATP production, maximum (MAX) respiration, reserve capacity and coupling efficiency. Conversely, glycolytic activity was increased after 1 month, most notably the enhanced glycolytic response to 25 mM glucose without any change in glycolytic capacity. Finally, calculation of bioenergetic health index (BHI) demonstrated that this potential diagnostic parameter was sensitive to cryopreservation. The present study has demonstrated for the first time that cryopreservation of primary immune cells modified their metabolism in a time-dependent fashion, indicated by attenuated aerobic respiration and enhanced glycolytic activity. Taken together, we recommend caution in the interpretation of bioenergetic responses or BHI in cryopreserved samples.

Sequential monitoring and stability of ex vivo-expanded autologous and non-autologous regulatory T cells following infusion in non-human primates

PubMed Central

Zhang, H.; Guo, H.; Lu, L.; Zahorchak, A. F.; Wiseman, R. W.; Raimondi, G.; Cooper, D. K. C.; Ezzelarab, M. B.; Thomson, A. W.

2016-01-01

Ex vivo-expanded cynomolgus monkey CD4+CD25+CD127− regulatory T cells (Treg) maintained Foxp3 demethylation status at the Treg-Specific Demethylation Region (TSDR), and potently suppressed T cell proliferation through 3 rounds of expansion. When CFSE- or VPD450-labeled autologous (auto) and non-autologous (non-auto) expanded Treg were infused into monkeys, the number of labeled auto-Treg in peripheral blood declined rapidly during the first week, but persisted at low levels in both normal and anti-thymocyte globulin plus rapamycin-treated (immunosuppressed; IS) animals for at least 3 weeks. By contrast, MHC-mismatched non-auto-Treg could not be detected in normal monkey blood or in blood of two out of the three IS monkeys by day 6 post-infusion. They were also more difficult to detect than auto-Treg in peripheral lymphoid tissue. Both auto- and non-auto-Treg maintained Ki67 expression early after infusion. Sequential monitoring revealed that adoptively-transferred auto-Treg maintained similarly high levels of Foxp3 and CD25 and low CD127 compared with endogenous Treg, although Foxp3 staining diminished over time in these non-transplanted recipients. Thus, infused ex vivo-expanded auto-Treg persist longer than MHC-mismatched non-auto-Treg in blood of non-human primates and can be detected in secondary lymphoid tissue. Host lymphodepletion and rapamycin administration did not consistently prolong the persistence of non-auto-Treg in these sites. PMID:25783759

Studies on the pathogenesis of fever. III. The leucocytic origin of endogenous pyrogen in acute inflammatory exudates.

PubMed

KING, M K; WOOD, W B

1958-02-01

The evolution of an acute inflammatory exudate produced in rabbits by the intraperitoneal injection of saline has been described. Evidence has been presented that polymorphonuclear leucocytes release endogenous pyrogen into the cell-free fluid of the exudate. Leucocytes from such exudates have also been shown to release pyrogen into the surrounding medium during incubation in vitro at 37 degrees C. The results of parallel cytological studies have provided evidence which suggests that the leucocytes give up their pyrogen while functionally intact. These observations add further support to the hypothesis that polymorphonuclear leucocytes play a significant role in the pathogenesis of fever.

Computer Aided Solution for Automatic Segmenting and Measurements of Blood Leucocytes Using Static Microscope Images.

PubMed

Abdulhay, Enas; Mohammed, Mazin Abed; Ibrahim, Dheyaa Ahmed; Arunkumar, N; Venkatraman, V

2018-02-17

Blood leucocytes segmentation in medical images is viewed as difficult process due to the variability of blood cells concerning their shape and size and the difficulty towards determining location of Blood Leucocytes. Physical analysis of blood tests to recognize leukocytes is tedious, time-consuming and liable to error because of the various morphological components of the cells. Segmentation of medical imagery has been considered as a difficult task because of complexity of images, and also due to the non-availability of leucocytes models which entirely captures the probable shapes in each structures and also incorporate cell overlapping, the expansive variety of the blood cells concerning their shape and size, various elements influencing the outer appearance of the blood leucocytes, and low Static Microscope Image disparity from extra issues outcoming about because of noise. We suggest a strategy towards segmentation of blood leucocytes using static microscope images which is a resultant of three prevailing systems of computer vision fiction: enhancing the image, Support vector machine for segmenting the image, and filtering out non ROI (region of interest) on the basis of Local binary patterns and texture features. Every one of these strategies are modified for blood leucocytes division issue, in this manner the subsequent techniques are very vigorous when compared with its individual segments. Eventually, we assess framework based by compare the outcome and manual division. The findings outcome from this study have shown a new approach that automatically segments the blood leucocytes and identify it from a static microscope images. Initially, the method uses a trainable segmentation procedure and trained support vector machine classifier to accurately identify the position of the ROI. After that, filtering out non ROI have proposed based on histogram analysis to avoid the non ROI and chose the right object. Finally, identify the blood leucocytes type using

A Flow Adhesion Assay to Study Leucocyte Recruitment to Human Hepatic Sinusoidal Endothelium Under Conditions of Shear Stress

PubMed Central

Shetty, Shishir; Weston, Christopher J.; Adams, David H.; Lalor, Patricia F.

2014-01-01

Leucocyte infiltration into human liver tissue is a common process in all adult inflammatory liver diseases. Chronic infiltration can drive the development of fibrosis and progression to cirrhosis. Understanding the molecular mechanisms that mediate leucocyte recruitment to the liver could identify important therapeutic targets for liver disease. The key interaction during leucocyte recruitment is that of inflammatory cells with endothelium under conditions of shear stress. Recruitment to the liver occurs within the low shear channels of the hepatic sinusoids which are lined by hepatic sinusoidal endothelial cells (HSEC). The conditions within the hepatic sinusoids can be recapitulated by perfusing leucocytes through channels lined by human HSEC monolayers at specific flow rates. In these conditions leucocytes undergo a brief tethering step followed by activation and firm adhesion, followed by a crawling step and subsequent transmigration across the endothelial layer. Using phase contrast microscopy, each step of this 'adhesion cascade' can be visualized and recorded followed by offline analysis. Endothelial cells or leucocytes can be pretreated with inhibitors to determine the role of specific molecules during this process. PMID:24686418

Autologous engineering of cartilage

PubMed Central

Emans, Pieter J.; van Rhijn, Lodewijk W.; Welting, Tim J. M.; Cremers, Andy; Wijnands, Nina; Spaapen, Frank; Voncken, J. Willem; Shastri, V. Prasad

2010-01-01

Treatment of full-thickness damage to hyaline cartilage is hampered by the limited availability of autologous healthy cartilage and the lengthy, cost-prohibitive cell isolation and expansion steps associated with autologous cartilage implantation (ACI). Here we report a strategy for de novo engineering of ectopic autologous cartilage (EAC) within the subperiosteal space (in vivo bioreactor), through the mere introduction of a biocompatible gel that might promote hypoxia-mediated chondrogenesis, thereby effectively overcoming the aforementioned limitations. The EAC is obtained within 3 wk post injection of the gel, and can be press-fit into an osteochondral defect where it undergoes remodeling with good lateral and subchondral integration. The implanted EAC showed no calcification even after 9 mo and attained an average O’Driscoll score of 11 (versus 4 for controls). An “on demand” autologous source of autologous cartilage with remodeling capacity is expected to significantly impact the clinical options in repair of trauma to articular cartilage. PMID:20133690

Involvement of leucocyte/endothelial cell interactions in anorexia nervosa.

PubMed

Víctor, Víctor M; Rovira-Llopis, Susana; Saiz-Alarcón, Vanessa; Sangüesa, Maria C; Rojo-Bofill, Luis; Bañuls, Celia; de Pablo, Carmen; Álvarez, Ángeles; Rojo, Luis; Rocha, Milagros; Hernández-Mijares, Antonio

2015-07-01

Anorexia nervosa is a common psychiatric disorder in adolescence and is related to cardiovascular complications. Our aim was to study the effect of anorexia nervosa on metabolic parameters, leucocyte-endothelium interactions, adhesion molecules and proinflammatory cytokines. This multicentre, cross-sectional, case-control study employed a population of 24 anorexic female patients and 36 controls. We evaluated anthropometric and metabolic parameters, interactions between leucocytes polymorphonuclear neutrophils (PMN) and human umbilical vein endothelial cells (HUVEC), proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and soluble cellular adhesion molecules (CAMs) including E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Anorexia nervosa was related to a decrease in weight, body mass index, waist circumference, systolic blood pressure, glucose, insulin and HOMA-IR, and an increase in HDL cholesterol. These effects disappeared after adjusting for BMI. Anorexia nervosa induced a decrease in PMN rolling velocity and an increase in PMN rolling flux and PMN adhesion. Increases in IL-6 and TNF-α and adhesion molecule VCAM-1 were also observed. This study supports the hypothesis of an association between anorexia nervosa, inflammation and the induction of leucocyte-endothelium interactions. These findings may explain, in part at least, the increased risk of vascular disease among patients with anorexia nervosa. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Automated processing of leucocyte-poor platelet concentrates.

PubMed

Tandy, N P; Seghatchian, M J; Bessos, H

1992-10-01

In view of transfusion reactions and alloimmunization associated with leucocyte contamination of platelet concentrates (PC), there is a general move towards the production of leuco-poor PC. This goal is currently pursued by the production of various PC using buffy coat and apheresis techniques. Although there is no overall consensus on the meaning of 'leuco-poor', by assuming that this refers to a level of 5-50 x 10(7) leucocytes per PC, we were able to make comparisons with available systems used in Europe. In addition to platelet and white cell counts, other markers of PC quality were assessed in some cases. These included traditional markers (such as hypotonic stress response, pH, and lactate and beta-thromboglobulin levels) and newer markers (such as glycocalicin and plasma von Willebrand factor levels). Our preliminary results showed appreciable differences in platelet and white cell content of PC prepared by various types of apheresis equipment. Appreciable differences in the quality of stored PC were also observed between routine PC (non-leuco-poor and buffy coat and apheresed PC (leuco-poor).

Trypanosoma cruzi: sequence of phagocytosis and cytotoxicity by human polymorphonuclear leucocytes.

PubMed Central

Rimoldi, M T; Cardoni, R L; Olabuenaga, S E; de Bracco, M M

1981-01-01

We have studied the relationship between phagocytosis and cytotoxicity of human polymorphonuclear leucocytes (PMN) to sensitized Trypanosoma cruzi. Assays were done simultaneously using [3H]-uridine labelled epimastigotes as target cells. Phagocytosis was evaluated by the uptake and cytotoxicity by the release of parasite associated [3H]-uridine. Both reactions reached maximum levels at the same effector- to target-cell ratio and antibody concentration. Uptake of epimastigotes by PMN was highest at 30 min and intracellular disruption and release of parasite debris took place later. In conditions that precluded repeated uptake of sensitized radiolabelled T. cruzi, the release profile of [3H]-uridine from PMN that contained intracellular parasites was similar to that of the standard cytotoxic assay. However, as the ingestion phase was separated from the release step, no lag in the onset of the reaction was observed. Although we cannot rule out extracellular killing, the results of this study demonstrate that the bulk of damaged T. cruzi epimastigotes had been previously internalized by the PMN. PMID:7016743

Phagocytosis and Respiratory Burst Activity in Lumpsucker (Cyclopterus lumpus L.) Leucocytes Analysed by Flow Cytometry

PubMed Central

Haugland, Gyri T.; Jakobsen, Ragnhild Aakre; Vestvik, Nils; Ulven, Kristian; Stokka, Lene; Wergeland, Heidrun I.

2012-01-01

In the present study, we have isolated leucocytes from peripheral blood, head kidney and spleen from lumpsucker (Cyclopterus lumpus L.), and performed functional studies like phagocytosis and respiratory burst, as well as morphological and cytochemical analyses. Different leucocytes were identified, such as lymphocytes, monocytes/macrophages and polymorphonuclear cells with bean shaped or bilobed nuclei. In addition, cells with similar morphology as described for dendritic cells in trout were abundant among the isolated leucocytes. Flow cytometry was successfully used for measuring phagocytosis and respiratory burst activity. The phagocytic capacity and ability were very high, and cells with different morphology in all three leucocyte preparations phagocytised beads rapidly. Due to lack of available cell markers, the identity of the phagocytic cells could not be determined. The potent non-specific phagocytosis was in accordance with a high number of cells positive for myeloperoxidase, an enzyme involved in oxygen-dependent killing mechanism present in phagocytic cells. Further, high respiratory burst activity was present in the leucocytes samples, verifying a potent oxygen- dependent degradation. At present, the specific antibody immune response could not be measured, as immunoglobulin or B-cells have not yet been isolated. Therefore, analyses of the specific immune response in this fish species await further clarification. The present study presents the first analyses of lumpsucker immunity and also the first within the order Scopaeniformes. PMID:23112870

Evaluation of droplet digital PCR for quantification of residual leucocytes in red blood cell concentrates.

PubMed

Doescher, A; Loges, U; Petershofen, E K; Müller, T H

2017-11-01

Enumeration of residual white blood cells in leucoreduced blood components is essential part of quality control. Digital PCR has substantially facilitated quantitative PCR and was thus evaluated for measurements of leucocytes. Target for quantification of leucocytes by digital droplet PCR was the blood group gene RHCE. The SPEF1 gene was added as internal control for the entire assay starting with automated DNA extraction. The sensitivity of the method was determined by serial dilutions of standard samples. Quality control samples were analysed within 24 h, 7 days and 6 months after collection. Routine samples from leucodepleted red blood cell concentrates (n = 150) were evaluated in parallel by flow-cytometry (LeucoCount) and by digital PCR. Digital PCR reliably detected at least 0·4 leucocytes per assay. The mean difference between PCR and flow-cytometric results from 150 units was -0·01 (±1·0). DNA samples were stable for up to at least six months. PCR measurement of leucocytes in samples from plasma and platelet concentrates also provided valid results in a pilot study. Droplet digital PCR to enumerate leucocytes offers an alternative for quality control of leucoreduced blood products. Sensitivity, specificity and reproducibility are comparable to flow-cytometry. The option to collect samples over an extended period of time and the automatization introduce attractive features for routine quality control. © 2017 International Society of Blood Transfusion.

Estimation of adult and neonatal RBC lifespans in anemic neonates using RBCs labeled at several discrete biotin densities.

PubMed

Kuruvilla, Denison J; Widness, John A; Nalbant, Demet; Schmidt, Robert L; Mock, Donald M; An, Guohua; Veng-Pedersen, Peter

2017-06-01

Prior conclusions that autologous neonatal red blood cells (RBC) have substantially shorter lifespans than allogeneic adult RBCs were not based on direct comparison of autologous neonatal vs. allogeneic adult RBCs performed concurrently in the same infant. Biotin labeling of autologous neonatal RBCs and allogeneic adult donor RBCs permits concurrent direct comparison of autologous vs. allogeneic RBC lifespan. RBCs from 15 allogeneic adult donors and from 15 very-low-birth-weight (VLBW) neonates were labeled at separate biotin densities and transfused simultaneously into the 15 neonates. Two mathematical models that account for the RBC differences were employed to estimate lifespans for the two RBC populations. Mean ± SD lifespan for adult allogeneic RBC was 70.1 ± 19.1 d, which is substantially shorter than the 120 d lifespan of both autologous and adult allogeneic RBC in healthy adults. Mean ± SD lifespan for neonatal RBC was 54.2 ± 11.3 d, which is only about 30% shorter than that of the adult allogeneic RBCs. This study provides evidence that extrinsic environmental factors primarily determine RBC survival (e.g., small bore of the capillaries of neonates, rate of oxygenation/deoxygenation cycles) rather than factors intrinsic to RBC.

Kinetics of leukocyte sequestration in the lungs of acutely septic primates: A study using sup 111 In-labeled autologous leukocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hangen, D.H.; Segall, G.M.; Harney, E.W.

1990-03-01

To further clarify the role of leukocytes in the pathogenesis of ARDS, we studied the localization and kinetics of leukocyte migration using 111In-labeled autologous white cell scans ({sup 111}In wbc scans) in four primates made acutely septic with infusions of Escherichia coli. Whole body images were obtained with a gamma camera and were acquired on computer every 15 min beginning immediately after the E. coli infusion. Simultaneous measurements of C5a and peripheral blood leukocyte count were also obtained. Within 5 min of initiating sepsis, three major events occurred: complement activation as measured by the production of C5a, a profound fallmore » in peripheral leukocyte count, and a significant increase in the sequestration of leukocytes in the lungs. The pulmonary sequestration reached a peak at 15 min with a mean of 152% of baseline activity. This sequestration consisted of a population that was predominantly neutrophils. Damage to the pulmonary capillary endothelium was demonstrated by an increase in extravascular lung water. The results support a role for neutrophils and complement as mediators in the pathogenesis of ARDS.« less

Increased collagenase and dipeptidyl peptidase I activity in leucocytes from healthy elderly people

PubMed Central

Llorente, L; Richaud-Patin, Y; Díaz-Borjón, A; Jakez-Ocampo, J; Alvarado-De La Barrera, C

1999-01-01

The incidence of infectious diseases increases with ageing. The enzymatic activity of leucocytes may have a relevant role in the morbidity and mortality due to infections in the elderly. In this study we have compared the activity of enzymes involved in the inflammatory response in leucocytes from young and elderly women. A total of 35 healthy females was studied, 20 volunteers aged 78–98 years (mean 89.1 years) and 15 young controls aged 19–34 years (mean 26 years). All of them were in good clinical condition, without any acute or chronic disease. Intracellular enzyme activity was analysed by flow cytometry in leucocytes from young and elderly women. The enzyme substrates employed were for oxidative burst, l-aminopeptidase, collagenase, cathepsin B, C, D and, G and dipeptidyl peptidase I. The intracellular enzyme activity assessed by flow cytometry in leucocytes from young and elderly women was similar, as far as oxidative burst, l-aminopeptidase, cathepsin B, C, D and G are concerned. An increased collagenase activity was detected in granulocytes from elders. The mean fluorescence channels for this enzyme corresponded to 86 ± 23 and 60 ± 15 in cells from elders and controls, respectively (P = 0.01224). An increased dipeptidyl peptidase I activity was detected in lymphocytes from elderly women. The corresponding values for this enzyme in elders and the young were 65.9 ± 43.3 and 17.3 ± 5, respectively (P = 0.0036). The proper functional activity of intracellular enzymes involved in inflammatory responses is likely to be determinant for successful ageing. PMID:10361229

Biologic response of human anterior cruciate ligamentocytes on collagen-patches to platelet-rich plasma formulations with and without leucocytes.

PubMed

Krismer, Anna M; Cabra, Romina S; May, Rahel D; Frauchiger, Daniela A; Kohl, Sandro; Ahmad, Sufian S; Gantenbein, Benjamin

2017-12-01

Due to the poor self-healing capacities of the anterior cruciate ligament, previous primary repair attempts have failed. To enhance biologic healing, platelet rich plasma and collagen scaffold have shown promise in animal models. Platelet rich plasma (PRP) is already used in several clinical applications although outcomes are quite debated. The purpose of this study was to examine the effects of different PRP formulations during 21 days: With leucocytes and pure PRP on human anterior cruciate ligament-derived ligamentocytes grown on collagen patches in 3D cell cultures in vitro. Three experimental groups were formed: 2.5% leucocyte rich PRP, 2.5% pure PRP, 20% leucocyte rich PRP, a negative control, and a positive control. Cell proliferation, cell phenotype on mRNA transcript level, and extracellular matrix production (total collagen and glycosaminoglycan content) were evaluated. DNA content and metabolic cell activity increased significantly in all groups on day 21 compared to day 7, except in the negative control. No changes in extracellular matrix production were detected. Different catabolic genes were induced depending on the concentration of leucocyte rich PRP. PRP with and without leucocytes treated anterior cruciate ligamentocytes significantly increased cell proliferation but not extracellular matrix production. However, the specific activation of different catabolic genes was dependent on the relative content of leucocytes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2733-2739, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Feasibility of Autologous Cord Blood Cells for Infants with Hypoxic-Ischemic Encephalopathy

PubMed Central

Cotten, C. Michael; Murtha, Amy P.; Goldberg, Ronald N.; Grotegut, Chad A.; Smith, P. Brian; Goldstein, Ricki F.; Fisher, Kimberley A.; Gustafson, Kathryn E.; Waters-Pick, Barbara; Swamy, Geeta K.; Rattray, Benjamin; Tan, Siddhartha; Kurtzberg, Joanne

2014-01-01

Objective To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE). Study design We enrolled infants in the Intensive Care Nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to four doses adjusted for volume and RBC content,1 – 5 × 107cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post- infusion vital signs. As exploratory analyses we compared cell recipients’ hospital outcomes (mortality, oral feeds at discharge) and one year survival with Bayley III scores ≥ 85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells. Results Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 milliliters. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1 year outcomes survived with scores ≥ 85. Conclusions Collection, preparation and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed. PMID:24388332

ILK mediates LPS-induced vascular adhesion receptor expression and subsequent leucocyte trans-endothelial migration.

PubMed

Hortelano, Sonsoles; López-Fontal, Raquel; Través, Paqui G; Villa, Natividad; Grashoff, Carsten; Boscá, Lisardo; Luque, Alfonso

2010-05-01

The inflammatory response to injurious agents is tightly regulated to avoid adverse consequences of inappropriate leucocyte accumulation or failed resolution. Lipopolysaccharide (LPS)-activated endothelium recruits leucocytes to the inflamed tissue through controlled expression of membrane-associated adhesion molecules. LPS responses in macrophages are known to be regulated by integrin-linked kinase (ILK); in this study, we investigated the role of ILK in the regulation of the LPS-elicited inflammatory response in endothelium. This study was performed on immortalized mouse endothelial cells (EC) isolated from lung and coronary vasculature. Cells were thoroughly characterized and the role of ILK in the regulation of the LPS response was investigated by suppressing ILK expression using siRNA and shRNA technologies. Phenotypic and functional analyses confirmed that the immortalized cells behaved as true EC. LPS induced the expression of the inflammatory genes E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). ILK knockdown impaired LPS-mediated endothelial activation by preventing the induction of ICAM-1 and VCAM-1. Blockade of the LPS-induced response inhibited the inflammatory-related processes of firm adhesion and trans-endothelial migration of leucocytes. ILK is involved in the expression of cell adhesion molecules by EC activated with the inflammatory stimulus LPS. This reduced expression modulates leucocyte adhesion to the endothelium and the extravasation process. This finding suggests ILK as a potential anti-inflammatory target for the development of vascular-specific treatments for inflammation-related diseases.

Leucocytes in human milk and lymphocyte subsets in cow's milk-allergic infants.

PubMed

Järvinen, Kirsi-Marjut; Suomalainen, Hanna

2002-08-01

The breast-fed infant ingests an average of 108 leucocytes per day, with breast-feeding often continuing for several months. The precise role of human milk leucocytes is still unresolved. Breast-feeding has been recommended for infants at high risk of allergy to prevent or delay the development of food allergies and atopic eczema. However, studies dealing with distinct immunologic factors in the mother's milk, and their effect on health status or development of allergies in the infant, are scarce. We evaluated the relationship between the cellular composition of human milk and the development of cow's milk allergy (CMA) in the breast-fed infant. Leucocyte subsets in the breast-fed infants were also measured. The study population comprised 61 breast-feeding mothers and their infants. Thirty-nine mothers each had a cow's milk-allergic infant, 10 had an infant with atopic dermatitis without CMA, and 12 mothers had a healthy infant. Leucocyte subsets in mothers' milk were counted using a light microscope and confirmed by flow cytometry. In infants, peripheral blood lymphocyte subsets were determined by flow cytometry and were correlated with the health status of the breast-fed infant and leucocyte composition of the mother's milk. Human milk was found to be a non-homogenous morphological entity. In the milk of mothers of infants with CMA, the proportion of macrophages was significantly smaller than in the mothers with infants without CMA (p = 0.036, t-test). Mothers with high proportions of neutrophils in their milk (> 20%) had significantly more often infants with CMA than did those with low proportions of neutrophils (p = 0.02; Fischer's exact test). Eosinophils comprising > 1% of milk cells were only detected in the mothers who had infants with CMA. Furthermore, the proportions of CD4+ T cells were positively correlated with the proportion of milk macrophages and negatively with the percentage of milk neutrophils and eosinophils. The proportions of total B cells and

Mononuclear leucocyte function tests in the assessment of the biocompatibility of peritoneal dialysis fluids.

PubMed

Brulez, H F; ter Wee, P M; Snijders, S V; Donker, A J; Verbrugh, H A

1999-12-01

Previous studies showed that the currently used dextrose based peritoneal dialysis fluids impair several leucocyte functions. To determine which in vitro mononuclear leucocyte (monocyte) function tests most clearly reflect the biocompatibility of peritoneal dialysis fluid. Monocytes were tested for phagocytic capacity, bactericidal activity, Fc and C3 receptor expression, and chemiluminescence response, and by analysis of the release of interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF alpha) in the presence of test fluids. Cytokine release was studied in an alternative dynamic in vitro peritoneal dialysis model in which monocytes were exposed to test fluid that was continuously equilibrated with an interstitial fluid-like medium through a microporous membrane. The chemiluminescence response by stressed monocytes was also tested after an 18 h recovery period. All tests were performed during or after exposure to different degrees of glycerol induced osmotic stress and after exposure to a 1% milk-whey derived, polypeptide enriched test fluid. Cells incubated in 0.1% gel Hanks buffer (GH) served as control. Osmotic stress induced impairment of leucocyte function was found by the chemiluminescence assay (mean (SEM): 179 (20)% v 138 (23)% after 30 minutes in 0.5% and 1.5% glycerol, respectively) and by the analysis of IL-8 released by monocytes (44 (9) ng in 0.7% glycerol v 40 (7) ng in 2.0% glycerol). Only the chemiluminescence assay showed a protective effect of polypeptides on leucocyte function (after > or = 60 minutes). If monocytes were allowed to recover in culture medium after exposure to test fluids, the changes in chemiluminescence response appeared to be reversible after a 30 minute exposure, but became more pronounced after 60 and 120 minutes. The phagocytosis and bacterial killing assays were less sensitive. The observations carried out with the phagocytosis assay did not correspond with the Fc or C3 receptor density data. The release of IL-8 by

Technical manual for manufacturing autologous fibrin tissue adhesive.

PubMed

Park, J J; Cintron, J R; Siedentop, K H; Orsay, C P; Pearl, R K; Nelson, R L; Abcarian, H

1999-10-01

The aim of this article is to provide a concise and simple technical manual for manufacturing autologous fibrin tissue adhesive derived from the precipitation of fibrinogen using a combination of ethanol and freezing for surgery. All materials and equipment needed to manufacture ethanol-based autologous fibrin tissue adhesive are listed. In addition, step-by-step instructions are provided to allow for easy and rapid fibrin adhesive production. Ethanol-based autologous fibrin tissue adhesive can be manufactured in under 60 minutes. Furthermore, at our institution the startup cost for manufacturing ethanol-based autologous fibrin tissue adhesive was under $2,500.00. Ethanol-based autologous fibrin tissue adhesive is a safe, reliable, and easily manufactured autologous fibrin tissue adhesive that can be made by a trained technician in any blood bank, pharmacy, or surgical laboratory.

Rapid cell separation with minimal manipulation for autologous cell therapies

NASA Astrophysics Data System (ADS)

Smith, Alban J.; O'Rorke, Richard D.; Kale, Akshay; Rimsa, Roberts; Tomlinson, Matthew J.; Kirkham, Jennifer; Davies, A. Giles; Wälti, Christoph; Wood, Christopher D.

2017-02-01

The ability to isolate specific, viable cell populations from mixed ensembles with minimal manipulation and within intra-operative time would provide significant advantages for autologous, cell-based therapies in regenerative medicine. Current cell-enrichment technologies are either slow, lack specificity and/or require labelling. Thus a rapid, label-free separation technology that does not affect cell functionality, viability or phenotype is highly desirable. Here, we demonstrate separation of viable from non-viable human stromal cells using remote dielectrophoresis, in which an electric field is coupled into a microfluidic channel using shear-horizontal surface acoustic waves, producing an array of virtual electrodes within the channel. This allows high-throughput dielectrophoretic cell separation in high conductivity, physiological-like fluids, overcoming the limitations of conventional dielectrophoresis. We demonstrate viable/non-viable separation efficacy of >98% in pre-purified mesenchymal stromal cells, extracted from human dental pulp, with no adverse effects on cell viability, or on their subsequent osteogenic capabilities.

Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial.

PubMed

Granel, Brigitte; Daumas, Aurélie; Jouve, Elisabeth; Harlé, Jean-Robert; Nguyen, Pierre-Sébastien; Chabannon, Christian; Colavolpe, Nathalie; Reynier, Jean-Charles; Truillet, Romain; Mallet, Stéphanie; Baiada, Antoine; Casanova, Dominique; Giraudo, Laurent; Arnaud, Laurent; Veran, Julie; Sabatier, Florence; Magalon, Guy

2015-12-01

In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability. We did an open-label, single arm, at one study site with 6-month follow-up among 12 female SSc patients with Cochin Hand Function Scale score >20/90. Autologous SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles. Primary outcome was the number and the severity of adverse events related to SVF-based therapy. Secondary endpoints were changes in hand disability and fibrosis, vascular manifestations, pain and quality of life from baseline to 2 and 6 months after cell therapy. All enrolled patients had surgery, and there were no dropouts or patients lost to follow-up. No severe adverse events occurred during the procedure and follow-up. Four minor adverse events were reported and resolved spontaneously. A significant improvement in hand disability and pain, Raynaud's phenomenon, finger oedema and quality of life was observed. This study outlines the safety of the autologous SVF cells injection in the hands of patients with SSc. Preliminary assessments at 6 months suggest potential efficacy needing confirmation in a randomised placebo-controlled trial on a larger population. GFRS (Groupe Francophone de Recherche sur la Sclérodermie). NCT01813279. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

Studies on the pathogensis of fever. IX. The production of endogenous pyrogen by polymorphonuclear leucocytes.

PubMed

KAISER, H K; WOOD, W B

1962-01-01

Determination of the dose-response curve for rabbit leucocytic pyrogen reveals a hyperthermic "ceiling" at which there is a marked insensitivity to dosage. This finding has important implications in relation to the quantitative assay of leucocytic pyrogen. Polymorphonuclear leucocytes separated from normal rabbit blood possess the capacity to produce less than 5 per cent of the pyrogen generated by the same number of rabbit granulocytes collected from acute peritoneal exudates. Blood granulocytes, separated in the cold from the buffy coat, contain no detectable preformed pyrogen. The amount of preformed pyrogen within exudate granulocytes represents but a small fraction of the pyrogen which the cells are capable of generating when incubated in normal saline at 37 degrees C. It is suggested that the active pyrogen is formed from an inactive precursor within the cells. Under the conditions tested, cell fragments of rabbit granulocytes fail to produce endogenous pyrogen. The fact that the production of pyrogen is blocked at 4 degrees C is in keeping with the hypothesis that it involves metabolic reactions within the cell.

Repair of facial nerve defects with decellularized artery allografts containing autologous adipose-derived stem cells in a rat model.

PubMed

Sun, Fei; Zhou, Ke; Mi, Wen-Juan; Qiu, Jian-Hua

2011-07-20

The purpose of this study was to investigate the effects of a decellularized artery allograft containing autologous adipose-derived stem cells (ADSCs) on an 8-mm facial nerve branch lesion in a rat model. At 8 weeks postoperatively, functional evaluation of unilateral vibrissae movements, morphological analysis of regenerated nerve segments and retrograde labeling of facial motoneurons were all analyzed. Better regenerative outcomes associated with functional improvement, great axonal growth, and improved target reinnervation were achieved in the artery-ADSCs group (2), whereas the cut nerves sutured with artery conduits alone (group 1) achieved inferior restoration. Furthermore, transected nerves repaired with nerve autografts (group 3) resulted in significant recovery of whisking, maturation of myelinated fibers and increased number of labeled facial neurons, and the latter two parameters were significantly different from those of group 2. Collectively, though our combined use of a decellularized artery allograft with autologous ADSCs achieved regenerative outcomes inferior to a nerve autograft, it certainly showed a beneficial effect on promoting nerve regeneration and thus represents an alternative approach for the reconstruction of peripheral facial nerve defects. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In Vivo Defection of Thrombi with Indium-111-Labeled Platelets

NASA Astrophysics Data System (ADS)

Price, David C.; Lipton, Martin J.; Lusby, Robert J.; Engelstad, Barry L.; Stoney, Ronald J.; Prager, Robert J.; Hartmeyer, James A.; Holly, Anne S.

1982-06-01

The use of Indium-111-oxine labeled autologous platelets has been explored in a dog-catheter model, as well as in a variety of clinical disorders in man. Newly forming experimental thrombi in dogs label well during the first 45-90 minutes, then lose both label and thrombus mass in a manner consistent with fibrinolysis. Thrombus weight is linearly related to In-111 activity, so that in vivo scintigraphy will be a practical method to evaluate various thrombotic stimuli and anti-thrombotic interventions experimentally. Preformed thrombus, however, labels poorly and cannot be detected by imaging in this dog model. Initial clinical experience with a variety of arterial, venous and cardiac thrombotic states is reviewed, indicating some of the strengths and same of the potential weaknesses of this new scintigraphic technique.

Social and environmental factors modulate leucocyte profiles in free-living Greylag geese (Anser anser)

PubMed Central

Ludwig, Sonja C.; Hemetsberger, Josef; Kotrschal, Kurt; Wascher, Claudia A.F.

2017-01-01

Background Blood parameters such as haematocrit or leucocyte counts are indicators of immune status and health, which can be affected, in a complex way, by exogenous as well as endogenous factors. Additionally, social context is known to be among the most potent stressors in group living individuals, therefore potentially influencing haematological parameters. However, with few exceptions, this potential causal relationship received only moderate scientific attention. Methods In a free-living and individually marked population of the highly social and long-lived Greylag goose, Anser anser, we relate variation in haematocrit (HCT), heterophils to lymphocytes ratio (H/L) and blood leucocyte counts to the following factors: intrinsic (sex, age, raising condition, i.e. goose- or hand-raised), social (pair-bond status, pair-bond duration and parental experience) and environmental (biologically relevant periods, ambient temperature) factors. Blood samples were collected repeatedly from a total of 105 focal birds during three biologically relevant seasons (winter flock, mating season, summer). Results We found significant relationships between haematological parameters and social as well as environmental factors. During the mating season, unpaired individuals had higher HCT compared to paired and family individuals and this pattern reversed in fall. Similarly, H/L ratio was positively related to pair-bond status in a seasonally dependent way, with highest values during mating and successful pairs had higher H/L ratio than unsuccessful ones. Also, absolute number of leucocytes tended to vary depending on raising condition in a seasonally dependent way. Discussion Haematology bears a great potential in ecological and behavioural studies on wild vertebrates. In sum, we found that HTC, H/L ratio and absolute number of leucocytes are modulated by social factors and conclude that they may be considered valid indicators of individual stress load. PMID:28070455

Leucocyte migration and nitroblue tetrazolium assay in Nigerian children with bacteremia and malaria parasitemia.

PubMed

Ganiyu, Arinola O; Abayomi, Odetunde B; Oludele, Adebiyi E; Gladys, Falusi A

2004-12-01

The prevalence of malaria parasitemia, bacteremia, certain hematological parameters, leucocyte migration index and nitroblue tetrazolium dye reduction were determined in 147 Nigerian children (4.24+/-2.88 years of age). Sixty (40.8%), 28(19.1%) and 26(17.7%) had malaria parasitemia only, bacteremia only and both malaria parasitemia and bacteremia, respectively. Four genera of bacteria, i.e E. coli, Proteus, Staphylococcus and Salmonella, were detected in subjects with both malaria parasitemia and bacteremia. The 4 bacterial genera and Klebsiella were detected in subjects with bacterial infection only. P. falciparum (68%), P. malariae (25%) and P. ovale (7%) were the species of malaria parasites identified in our subjects. Bacteremia was most prevalent in subjects with hemoglobin AA (HbAA) (60.7%) followed by HbAC (21.45%). Packed cell volume (PCV) and Hb concentration were similar in all groups but mean counts of red blood cells (RBC) and white blood cells (WBC) were statistically significantly lower in subjects with malaria parasites only compared to the controls. Leucocyte migration was significantly reduced in children with bacteremia only or both malaria parasitemia and bacteremia compared to controls, while the nitroblue tetrazolium assay was significantly reduced in children with bacteremia only. It may be concluded that malaria parasitemia significantly affects both leucocyte migration and nitroblue tetrazolium assay.

Phylogeny of lymphocyte heterogeneity: the cellular requirements for the mixed leucocyte reaction with channel catfish.

PubMed Central

Miller, N W; Deuter, A; Clem, L W

1986-01-01

Vigorous mixed leucocyte reactions (MLR) were obtained using channel catfish peripheral blood leucocytes (PBL) when equal numbers of responder and stimulator cells (5 X 10(5) cells each) were cocultured. The use of 2000 rads of X-irradiation was sufficient to block subsequent proliferative responses of the stimulator cells. The cellular requirements for channel catfish MLR responses were assessed by using three functionally distinct leucocyte subpopulations isolated from the PBL. B cells (sIg+ lymphocytes) and T cells (sIg- lymphocytes) were isolated by an indirect panning procedure employing a monoclonal antibody specific for channel catfish Ig. A third population, monocytes, was isolated or depleted by adherence to baby hamster kidney cell microexudate-coated surfaces or adherence to Sephadex G-10, respectively. The results indicated that only the T cells were able to respond in the fish MLR, with monocytes being required as accessory cells. In contrast, all three cell types could function as stimulator cells. In addition, it was observed that low in vitro culture temperatures inhibited the generation of channel catfish MLRs, thereby supporting the contention that low temperature immunosuppression in fish results from a preferential inhibition of the generation of primary T-cell responses. PMID:2944817

Autologous Doping with Cryopreserved Red Blood Cells – Effects on Physical Performance and Detection by Multivariate Statistics

PubMed Central

Malm, Christer B.; Khoo, Nelson S.; Granlund, Irene; Lindstedt, Emilia; Hult, Andreas

2016-01-01

The discovery of erythropoietin (EPO) simplified blood doping in sports, but improved detection methods, for EPO has forced cheating athletes to return to blood transfusion. Autologous blood transfusion with cryopreserved red blood cells (RBCs) is the method of choice, because no valid method exists to accurately detect such event. In endurance sports, it can be estimated that elite athletes improve performance by up to 3% with blood doping, regardless of method. Valid detection methods for autologous blood doping is important to maintain credibility of athletic performances. Recreational male (N = 27) and female (N = 11) athletes served as Transfusion (N = 28) and Control (N = 10) subjects in two different transfusion settings. Hematological variables and physical performance were measured before donation of 450 or 900 mL whole blood, and until four weeks after re-infusion of the cryopreserved RBC fraction. Blood was analyzed for transferrin, iron, Hb, EVF, MCV, MCHC, reticulocytes, leucocytes and EPO. Repeated measures multivariate analysis of variance (MANOVA) and pattern recognition using Principal Component Analysis (PCA) and Orthogonal Projections of Latent Structures (OPLS) discriminant analysis (DA) investigated differences between Control and Transfusion groups over time. Significant increase in performance (15 ± 8%) and VO2max (17 ± 10%) (mean ± SD) could be measured 48 h after RBC re-infusion, and remained increased for up to four weeks in some subjects. In total, 533 blood samples were included in the study (Clean = 220, Transfused = 313). In response to blood transfusion, the largest change in hematological variables occurred 48 h after blood donation, when Control and Transfused groups could be separated with OPLS-DA (R2 = 0.76/Q2 = 0.59). RBC re-infusion resulted in the best model (R2 = 0.40/Q2 = 0.10) at the first sampling point (48 h), predicting one false positive and one false negative. Over all, a 25% and 86% false positives ratio was

Effects of dietary n-3 fatty acids on Toll-like receptor activation in primary leucocytes from Atlantic salmon (Salmo salar).

PubMed

Arnemo, Marianne; Kavaliauskis, Arturas; Andresen, Adriana Magalhaes Santos; Bou, Marta; Berge, Gerd Marit; Ruyter, Bente; Gjøen, Tor

2017-08-01

The shortage of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the international markets has led to increasing substitution of fish oil by plant oils in Atlantic salmon (Salmo salar) feed and thereby reducing the EPA and DHA content in salmon. However, the minimum required levels of these fatty acids in fish diets for securing fish health are unknown. Fish were fed with 0, 1 or 2% EPA or DHA alone or in combination of both over a period, growing from 50 to 400 g. Primary head kidney leucocytes were isolated and stimulated with Toll-like receptor (TLR) ligands to determine if EPA and DHA deficiency can affect expression of important immune genes and eicosanoid production. Several genes related to viral immune response did not vary between groups. However, there was a tendency that the high-level EPA and DHA groups expressed lower levels of IL-1β in non-stimulated leucocytes. These leucocytes were also more responsive to the TLR ligands, inducing higher expression levels of IL-1β and Mx1 after stimulation. The levels of prostaglandin E2 and leukotriene B4 in serum and media from stimulated leucocytes were lower in both low and high EPA and DHA groups. In conclusion, leucocytes from low EPA and DHA groups seemed to be less responsive towards immunostimulants, like TLR ligands, indicating that low levels or absence of dietary EPA and DHA may have immunosuppressive effects.

What is autologous blood transfusion?

PubMed

Sansom, A

1993-07-01

The word autologous is Greek in origin. The definition is exact 'autos' means self and 'logus' means relation. Thus, the meaning is 'related to self'. Autologous blood transfusion, which also is referred to frequently but incorrectly and imprecisely as auto transfusion, designates the reinfusion of blood or blood components to the same individual from whom they were taken. Homologous blood is blood or blood components, from another human donor, taken and stored for later transfusion as required.

Chronic bacterial osteomyelitis: prospective comparison of (18)F-FDG imaging with a dual-head coincidence camera and (111)In-labelled autologous leucocyte scintigraphy.

PubMed

Meller, J; Köster, G; Liersch, T; Siefker, U; Lehmann, K; Meyer, I; Schreiber, K; Altenvoerde, G; Becker, W

2002-01-01

Indium-111-labelled white blood cells ((111)In-WBCs) are currently considered the tracer of choice in the diagnostic work-up of suspected active chronic osteomyelitis (COM). Previous studies in a limited number of patients, performed with dedicated PET systems, have shown that [(18)F]2'-deoxy-2-fluoro- D-glucose (FDG) imaging may offer at least similar diagnostic accuracy. The aim of this prospective study was to compare FDG imaging with a dual-head coincidence camera (DHCC) and (111)In-WBC imaging in patients with suspected COM. Thirty consecutive non-diabetic patients with possible COM underwent combined skeletal scintigraphy (30/30 patients), (111)In-WBC imaging (28/30 patients) and FDG-PET with a DHCC (30/30 patients). During diagnostic work-up, COM was proven in 11/36 regions of suspected skeletal infection and subsequently excluded in 25/36 regions. In addition, soft tissue infection was present in five patients and septic arthritis in three. (111)In-WBC imaging in 28 patients was true positive in 2/11 regions with proven COM and true negative in 21/23 regions without further evidence of COM. False-positive results occurred in two regions and false-negative results in nine regions suspected for COM. Most of the false-negative results (7/9) occurred in the central skeleton. If the analysis was restricted to the 18 regions with available histology ( n=17) or culture ( n=1), (111)In-WBC imaging was true positive in 2/18 regions, true negative in 8/18 regions, false negative in 7/18 regions and false positive in 1/18 regions. FDG-DHCC imaging was true positive in 11/11 regions with proven COM and true negative in 23/25 regions without further evidence of COM. False-positive results occurred in two regions. If the analysis was restricted to the 19 regions with available histology ( n=18) or culture ( n=1), FDG-DHCC imaging was true positive in 9/9 regions with proven COM and true negative in 10/10 regions without further evidence of COM. It is concluded that FDG

Pathological analysis, detection of antigens, FasL expression analysis and leucocytes survival analysis in tilapia (Oreochromis niloticus) after infection with green fluorescent protein labeled Streptococcus agalactiae.

PubMed

Wang, Jingyuan; Wu, Jinying; Yi, Liyuan; Hou, Zengxin; Li, Wensheng

2017-03-01

The pathogenesis of Streptococcus agalactiae infection in tilapia has not been fully described. To understand this, we investigated the clinic-pathological features of acute experimental septicemia in tilapia (Oreochromis niloticus) after receiving an intra-peritoneal injection with S. agalactiae THN-1901GFP. Immunohistochemistry and sections of pathological tissues were used to estimate the level of damage in the head-kidney, liver, spleen and trunk-kidney. The expression of FasL was analyzed by western blotting in these samples based on their damage levels. Leucocytes were isolated from the head-kidney and incubated with S. agalactiae THN-1901GFP. Then, phagocytosis, programmed cell death and the expression of FasL were analyzed. The infected tissues showed varying degrees of necrosis and histolysis. The serous membrane of the intestine was dissolved by S. agalactiae THN-1901GFP. Antigens of S. agalactiae THN-1901GFP accumulated in different parts of the infected organs. In the head-kidney and spleen, the expression of FasL was up-regulated in parallel with increased tissue damage. After being incubated with S. agalactiae THN-1901GFP, the phagocytic capacity and ability were both very high and the expression of FasL remained high in leucocytes. S. agalactiae THN-1901GFP was able to survive for a long period of time after being engulfed by phagocytic cells. These findings offer insight into the pathogenesis of S. agalactiae infection in tilapia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of the effects of xenon and sevoflurane anaesthesia on leucocyte function in surgical patients: a randomized trial.

PubMed

Fahlenkamp, A V; Coburn, M; Rossaint, R; Stoppe, C; Haase, H

2014-02-01

While most anaesthetics are known to suppress immune reactions, data from experimental studies indicate the enhancement of reactivity to inflammatory stimulators under xenon treatment. We investigated the effect of xenon anaesthesia on leucocyte function in surgical patients. We performed a subgroup analysis of subjects undergoing xenon or sevoflurane anaesthesia in a randomized clinical trial. After oral premedication with midazolam, two separate blood samples were obtained from subjects undergoing elective abdominal surgery, directly before and 1 h after induction of anaesthesia. General anaesthesia was maintained with either 60% xenon or 2.0% sevoflurane in 30% O2. Leucocyte count, phagocytotic function, and pro-inflammatory cytokine release after ex vivo lipopolysaccharide (LPS) stimulation were determined. Except for lymphocyte numbers, leucocyte subpopulations did not differ between the groups. Phagocytosis and oxidative burst of granulocytes were reduced in both groups after 1 h of anaesthesia, whereas monocytes were not affected. Pro-inflammatory cytokine release in response to LPS was not affected. In vivo, xenon and sevoflurane anaesthesia did not have a pro-inflammatory effect, at least in combination with the types of surgery performed in this study. Notably, the impact of xenon anaesthesia did not differ significantly from sevoflurane anaesthesia with regard to leucocyte function. However, an underestimation of treatment effects due to limited sample sizes cannot be fully excluded.

Prevalence and correlates of hospital-based autologous blood programs: a statewide survey.

PubMed

Hull, A L; Neuhauser, D V; Goodnough, L T

1992-05-01

To identify potential barriers to use of autologous blood procurement to minimize homologous blood transfusion needs during elective surgery, the authors conducted a telephone survey of 120 blood bank directors, representing 138 Ohio hospitals. The prevalence of autologous blood procurement facilities, estimated volume of autologous blood, and attitudes and perceptions of the directors toward autologous blood predeposit programs were assessed. Analysis of the data indicated that 30% of Ohio hospitals have autologous blood procurement facilities; larger hospitals were more likely to have this facility. Overall, 5.5% of transfusions involve predeposited autologous blood. No significant differences were found according to hospital bed size or whether the hospital had a procurement facility. Blood bank directors perceived surgeons to be knowledgeable about autologous predeposit; patient demand and surgical practice were felt to be more effective in promoting the use of autologous blood at the hospital than were blood bank efforts. Directors who had autologous predeposit procurement facilities perceived that the facility provided a marketing advantage. Respondents from larger hospitals were more likely to perceive that these programs could be financially self-sufficient. The authors conclude that an economic cost-benefit analysis of hospital-based autologous blood procurement programs is important. Positive findings may influence transfusion services to adopt autologous blood procurement programs, whereas negative findings may convince hospitals that community blood donor facilities can provide better autologous blood procurement.

MHC class I antigens and tumour-infiltrating leucocytes in laryngeal cancer: long-term follow-up.

PubMed Central

Esteban, F.; Redondo, M.; Delgado, M.; Garrido, F.; Ruiz-Cabello, F.

1996-01-01

Alteration in MHC class I expression may be used by cancer cells to avoid immune destruction. Much experimental evidence supports this idea, although survival studies are very scarce. To investigate whether the presence or absence of HLA-A, -B and -C antigens in laryngeal carcinoma influences survival, a series of 60 primary laryngeal tumours treated surgically and normal tissues were evaluated in frozen sections for the expression of MHC class I antigens and tumour-infiltrating leucocytes (CD3, CD4, CD8, CD11b, CD1, CD20 and CD16), using monoclonal antibodies and the APAAP, technique. Long-term follow-up from the patients is available, ranging from 6 to 10 years. Thirteen tumours presented total HLA-ABC loss, five selective losses of HLA-A antigens and one absence of HLA-B antigens. Total losses were statistically associated with several clinical and pathological parameters, but there were no differences regarding tumour-infiltrating leucocytes. After conducting a prospective study, only T and N staging and scoring according to Glanz's malignancy classification were found to be independently related to patients' outcome. From our data, we conclude that neither complete loss of HLA class I antigens nor tumour-infiltrating leucocytes appear to influence survival in squamous cell carcinoma of the larynx. PMID:8956796

Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions--a pilot study.

PubMed

Geburek, Florian; Mundle, Kathrin; Conrad, Sabine; Hellige, Maren; Walliser, Ulrich; van Schie, Hans T M; van Weeren, René; Skutella, Thomas; Stadler, Peter M

2016-02-01

Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used to treat equine tendinopathies. Up to now, knowledge about the fate of autologous AT-MSCs after intralesional injection into equine superficial digital flexor tendons (SDFTs) is very limited. The purpose of this study was to monitor the presence of intralesionally injected autologous AT-MSCs labelled with superparamagnetic iron oxide (SPIO) nanoparticles and green fluorescent protein (GFP) over a staggered period of 3 to 9 weeks with standing magnetic resonance imaging (MRI) and histology. Four adult warmblood horses received a unilateral injection of 10 × 10(6) autologous AT-MSCs into surgically created front-limb SDFT lesions. Administered AT-MSCs expressed lentivirally transduced reporter genes for GFP and were co-labelled with SPIO particles in three horses. The presence of AT-MSCs in SDFTs was evaluated by repeated examinations with standing low-field MRI in two horses and post-mortem in all horses with Prussian blue staining, fluorescence microscopy and with immunofluorescence and immunohistochemistry using anti-GFP antibodies at 3, 5, 7 and 9 weeks after treatment. AT-MSCs labelled with SPIO particles were detectable in treated SDFTs during each MRI in T2*- and T1-weighted sequences until the end of the observation period. Post-mortem examinations revealed that all treated tendons contained high numbers of SPIO- and GFP-labelled cells. Standing low-field MRI has the potential to track SPIO-labelled AT-MSCs successfully. Histology, fluorescence microscopy, immunofluorescence and immunohistochemistry are efficient tools to detect labelled AT-MSCs after intralesional injection into surgically created equine SDFT lesions. Intralesional injection of 10 × 10(6) AT-MSCs leads to the presence of high numbers of AT-MSCs in and around surgically created tendon lesions for up to 9 weeks. Integration of injected AT-MSCs into healing tendon tissue is an essential pathway after intralesional

Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV.

PubMed

Tebas, Pablo; Stein, David; Tang, Winson W; Frank, Ian; Wang, Shelley Q; Lee, Gary; Spratt, S Kaye; Surosky, Richard T; Giedlin, Martin A; Nichol, Geoff; Holmes, Michael C; Gregory, Philip D; Ando, Dale G; Kalos, Michael; Collman, Ronald G; Binder-Scholl, Gwendolyn; Plesa, Gabriela; Hwang, Wei-Ting; Levine, Bruce L; June, Carl H

2014-03-06

CCR5 is the major coreceptor for human immunodeficiency virus (HIV). We investigated whether site-specific modification of the gene ("gene editing")--in this case, the infusion of autologous CD4 T cells in which the CCR5 gene was rendered permanently dysfunctional by a zinc-finger nuclease (ZFN)--is safe. We enrolled 12 patients in an open-label, nonrandomized, uncontrolled study of a single dose of ZFN-modified autologous CD4 T cells. The patients had chronic aviremic HIV infection while they were receiving highly active antiretroviral therapy. Six of them underwent an interruption in antiretroviral treatment 4 weeks after the infusion of 10 billion autologous CD4 T cells, 11 to 28% of which were genetically modified with the ZFN. The primary outcome was safety as assessed by treatment-related adverse events. Secondary outcomes included measures of immune reconstitution and HIV resistance. One serious adverse event was associated with infusion of the ZFN-modified autologous CD4 T cells and was attributed to a transfusion reaction. The median CD4 T-cell count was 1517 per cubic millimeter at week 1, a significant increase from the preinfusion count of 448 per cubic millimeter (P<0.001). The median concentration of CCR5-modified CD4 T cells at 1 week was 250 cells per cubic millimeter. This constituted 8.8% of circulating peripheral-blood mononuclear cells and 13.9% of circulating CD4 T cells. Modified cells had an estimated mean half-life of 48 weeks. During treatment interruption and the resultant viremia, the decline in circulating CCR5-modified cells (-1.81 cells per day) was significantly less than the decline in unmodified cells (-7.25 cells per day) (P=0.02). HIV RNA became undetectable in one of four patients who could be evaluated. The blood level of HIV DNA decreased in most patients. CCR5-modified autologous CD4 T-cell infusions are safe within the limits of this study. (Funded by the National Institute of Allergy and Infectious Diseases and others

Chimeric autologous/allogeneic constructs for skin regeneration.

PubMed

Rasmussen, Cathy Ann; Tam, Joshua; Steiglitz, Barry M; Bauer, Rebecca L; Peters, Noel R; Wang, Ying; Anderson, R Rox; Allen-Hoffmann, B Lynn

2014-08-01

The ideal treatment for severe cutaneous injuries would eliminate the need for autografts and promote fully functional, aesthetically pleasing autologous skin regeneration. NIKS progenitor cell-based skin tissues have been developed to promote healing by providing barrier function and delivering wound healing factors. Independently, a device has recently been created to "copy" skin by harvesting full-thickness microscopic tissue columns (MTCs) in lieu of autografts traditionally harvested as sheets. We evaluated the feasibility of combining these two technologies by embedding MTCs in NIKS-based skin tissues to generate chimeric autologous/allogeneic constructs. Chimeric constructs have the potential to provide immediate wound coverage, eliminate painful donor site wounds, and promote restoration of a pigmented skin tissue possessing hair follicles, sweat glands, and sebaceous glands. After MTC insertion, chimeric constructs and controls were reintroduced into air-interface culture and maintained in vitro for several weeks. Tissue viability, proliferative capacity, and morphology were evaluated after long-term culture. Our results confirmed successful MTC insertion and integration, and demonstrated the feasibility of generating chimeric autologous/allogeneic constructs that preserved the viability, proliferative capacity, and structure of autologous pigmented skin. These feasibility studies established the proof-of-principle necessary to further develop chimeric autologous/allogeneic constructs for the treatment of complex skin defects. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF).

PubMed

Dohan Ehrenfest, David M; Rasmusson, Lars; Albrektsson, Tomas

2009-03-01

The topical use of platelet concentrates is recent and its efficiency remains controversial. Several techniques for platelet concentrates are available; however, their applications have been confusing because each method leads to a different product with different biology and potential uses. Here, we present classification of the different platelet concentrates into four categories, depending on their leucocyte and fibrin content: pure platelet-rich plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; leucocyte- and platelet-rich plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan or GPS PRP; pure plaletet-rich fibrin (P-PRF), such as Fibrinet; and leucocyte- and platelet-rich fibrin (L-PRF), such as Choukroun's PRF. This classification should help to elucidate successes and failures that have occurred so far, as well as providing an objective approach for the further development of these techniques.

High-throughput deep screening and identification of four peripheral leucocyte microRNAs as novel potential combination biomarkers for preeclampsia

PubMed Central

Wang, Yonghong; Yang, Xukui; Yang, Yuanyuan; Wang, Wenjun; Zhao, Meiling; Liu, Huiqiang; Li, Dongyan; Hao, Min

2016-01-01

Objective: To identify the specific microRNA (miRNA) biomarkers of preeclampsia (PE), the miRNA profiles analysis were performed. Study Design: The blood samples were obtained from five PE patients and five normal healthy pregnant women. The small RNA profiles were analyzed to identify miRNA expression levels and find out miRNAs that may associate with PE. The quantitative reverse transcriptase–PCR (qRT-PCR) assay was used to validate differentially expressed peripheral leucocyte miRNAs in a new cohort. Result: The data analysis showed that 10 peripheral leucocyte miRNAs were significantly differently expressed in severe PE patients. Four differently expressed miRNAs were successfully validated using qRT-PCR method. Conclusion: We successfully constructed a model with high accuracy to predict PE. A combination of four peripheral leucocyte miRNAs has great potential to serve as diagnostic biomarkers of PE. PMID:26675000

The effect of thyroid antigens on the in vitro migration of leucocytes from patients with Hashimoto thyroiditis

PubMed Central

Calder, Elizabeth A.; McLeman, Dena; Barnes, E. W.; Irvine, W. J.

1972-01-01

A total of fifty-two patients with Hashimoto thyroiditis were tested for delayed hypersensitivity to thyroid antigens using the leucocyte migration test. The percentage of patients showing abnormal migration in the presence of crude thyroid extract, thyroglobulin, thyroid mitochondria and thyroid microsomes was 75, 44, 54 and 34% respectively. Fifty-three control patients were studied concurrently with the same antigens and the percentage showing abnormal migration was 4, 6, 6 and 6% respectively. The antigenic activity of the mitochondrial fraction was not organ specific; both liver and kidney mitochondria interfered with the migration of leucocytes from patients with Hashimoto thyroiditis. PMID:4568149

An Improved method for separation of leucocytes from peripheral blood of the little skate (Leucoraja erinacea)

PubMed Central

Tomana, Mitsuru; Parton, Angela; Barnes, David W.

2008-01-01

Cartilaginous fish, especially sharks, rays and skates (elasmobranchs) hold interest as comparative models in immunology because they are thought to be among the organisms most closely related to the ancestor animal that first developed acquired immunity. The aim of this study was to improve methods used for the purification of viable leucocytes from peripheral blood of elasmobranchs. Here we describe modifications of density gradient centrifugation and medium formulation that improve isolation and analysis of highly-purified leucocytes from peripheral blood of a model elasmobranch, Leucoraja erinacea, the little skate. These techniques contribute to the preparation of elasmobranch immune cells that can be reliably analyzed by a variety of means, including the study of immune function. PMID:18474431

Assessing commercial opportunities for autologous and allogeneic cell-based products.

PubMed

Smith, Devyn M

2012-09-01

The two primary cell sources used to produce cell-based therapies are autologous (self-derived) and allogeneic (derived from a donor). This analysis attempts to compare and contrast the two approaches in order to understand whether there is an emerging preference in the market. While the current clinical trials underway are slightly biased to autologous approaches, it is clear that both cell-based approaches are being aggressively pursued. This analysis also breaks down the commercial advantages of each cell-based approach, comparing both cost of goods and the ideal indication type for each. While allogeneic therapies have considerable advantages over autologous therapies, they do have a distinct disadvantage regarding potential immunogenicity. The introduction of the hybrid autologous business model provides the ability for autologous-based therapies to mitigate some of the advantages that allogeneic cell-based therapies enjoy, including cost of goods. Finally, two case studies are presented that demonstrate that there is sufficient space for both autologous and allogeneic cell-based therapies within a single disease area.

In vitro polarization of carp leucocytes in response to the blood fluke Sanguinicola inermis Plehn, 1905 (Trematoda: Sanguinicolidae).

PubMed

Richards, D T; Hoole, D; Lewis, J W; Ewens, E; Arme, C

1996-05-01

An in vitro assay was used to determine the effects of Sanguinicola inermis adults and cercariae on the polarization responses of pronephric leucocytes of carp. Leucocytes were isolated and exposed to live adult flukes or cercariae for up to 48 h. Differences in polarization responses were related to the presence of the parasite, the presence or absence of carp serum and the time of incubation. The mean proportions of cells exhibiting polarization in unstimulated controls ranged from 5 to 30% over the experimental period. Within 15 min of exposure to adults or cercariae, significant increases in mean polarization responses were observed of up to 75% and levels remained higher than control values for over 24 h. Overall, the presence of normal carp serum, either untreated or heat inactivated, did not enhance the polarization responses of leucocytes incubated with only cercariae or adults. However, between 0.25 and 3 h, the presence of carp serum with cercariae significantly enhanced polarization responses when compared with cells incubated with cercariae alone.

Studies on the pathogenesis of fever. IV. The site of action of leucocytic and circulating endogenous pyrogen.

PubMed

KING, M K; WOOD, W B

1958-02-01

By means of a method designed to compare the febrile responses produced by intracarotid and intravenous injections, the endogenous pyrogen, which is contained in leucocytic exudates and is present in the serum of rabbits 2 hours after intravenous injections of typhoid vaccine, has been shown to act directly upon the thermoregulatory centers of the brain. In contrast, the exogenous bacterial pyrogen present in serum obtained 5 minutes after vaccine injections was found to act by a different and less direct mechanism. These observations add strong support to the original hypothesis that endogenous pyrogen, presumably derived from polymorphonuclear leucocytes, is an essential factor in the pathogenesis of endotoxin fever.

Adherence of carp leucocytes to adults and cercariae of the blood fluke Sanguinicola inermis.

PubMed

Richards, D T; Hoole, D; Lewis, J W; Ewens, E; Arme, C

1996-03-01

Live adult and cercarial stages of Sanguinicola inermis Plehn, 1905 (Trematoda:Sanguinicolidae) were maintained in vitro in the presence of carp (Cyprinus carpio L.) leucocytes. Cells and parasites were fixed at intervals from 0.25 to 48 h and examined using light microscopy, SEM and TEM. Within 12 h of exposure, leucocytes were found attached to cercariae although, by 24 h, fewer cells were found attached to postcercarial, juvenile adult stages that had shed their tails. Neutrophils and macrophages were found attached to the damaged tegument of cercarie that had not transformed by 48 h. Few cells were attached to the tegument of adult flukes that were alive when fixed. However, there was extensive tegumental damage and numerous cells were attached to adult flukes that had died before fixation. The results are discussed with reference to parasite survival within the vascular system of the host.

[The present possibilities for routine use of blood-saving measures from the anesthesiologic point of view--theoretical bases and clinical practice. III. Autologous blood donation, autologous donation criteria and organizational measures].

PubMed

Singbartl, G; Schleinzer, W

1994-01-01

This third part of a review on "Autologous Transfusion" deals with preoperative autologous blood donation, with supplemental pharmaco-therapy, with election criteria of the patient as well as with the organizational measures to be taken into account if an intensive autologous predeposit programme is routinely applied. Donation of an autologous predeposit aims at supplying the patient with autologous blood and autologous plasma, respectively, according to the expected blood loss and in order to reduce the need for homologous transfusion. Important aspects, which have to be considered if applying a routine autologous donation programme refer both to the election criteria of the patient and to the organizational programme and measures to be considered. Data in the literature reveal, that the risk of side effects for the patient (who is both the donor and the receiver of the (autologous) blood) during and after donation of an autologous predeposit is definitely not greater than the risk reported for otherwise healthy homologous volunteers. In our opinion, this means, that a patient who has been declared eligible for an elective operative intervention which makes homologous transfusion very probable, can be considered eligible for donating an autologous predeposit; additionally, he should also be eligible for acute normovolemic hemodilution, as donating an autologous predeposit with accompanying volume substitution of the predeposit 'is under hemodynamic aspects' nothing else than an acute and preoperatively performed normovolemic hemodilution. Analysing the data so far reported, volume substitution of the autologous predeposit appears to be a very important component for the patient's safety.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet-, leucocyte- and red cell-derived microparticles in stored whole blood, with and without leucofiltration, with and without ionising radiation

PubMed Central

Saito, Shunnichi; Ngoma, Alain M.; Ono, Takako; Ohto, Hitoshi

2018-01-01

Background Storage lesion, including microparticle formation, has been partially characterised in whole blood, but not in all combinations of pre-storage leucofiltration and/or irradiation. Materials and methods Single-donor whole blood products were processed into four subunits: with and without leucofiltration, with and without X-irradiation (25 Gy). Platelet-, leucocyte-, and erythrocyte-derived microparticles and free haemoglobin were measured periodically throughout 42 days of storage. Results Pre-storage leucofiltration substantially reduced platelet- and leucocyte-derived microparticle counts throughout storage. Irradiation, in contrast, had no significant effect on microparticle counts. A gate for all microparticles showed a substantial time-dependent increase in unfiltered whole blood. A time-dependent increase in free haemoglobin was greatest in unfiltered, irradiated whole blood. Discussion This study indicates that leucofiltration can prevent the formation of leucocyte- and platelet-derived microparticles, and might reduce haemolysis in irradiated whole blood, either by removing factors that provoke haemolysis, or by selective retention of senescent or effete red cells most prone to haemolysis. PMID:27893349

Platelet-, leucocyte- and red cell-derived microparticles in stored whole blood, with and without leucofiltration, with and without ionising radiation.

PubMed

Saito, Shunnichi; Nollet, Kenneth E; Ngoma, Alain M; Ono, Takako; Ohto, Hitoshi

2018-02-01

Storage lesion, including microparticle formation, has been partially characterised in whole blood, but not in all combinations of pre-storage leucofiltration and/or irradiation. Single-donor whole blood products were processed into four subunits: with and without leucofiltration, with and without X-irradiation (25 Gy). Platelet-, leucocyte-, and erythrocyte-derived microparticles and free haemoglobin were measured periodically throughout 42 days of storage. Pre-storage leucofiltration substantially reduced platelet- and leucocyte-derived microparticle counts throughout storage. Irradiation, in contrast, had no significant effect on microparticle counts. A gate for all microparticles showed a substantial time-dependent increase in unfiltered whole blood. A time-dependent increase in free haemoglobin was greatest in unfiltered, irradiated whole blood. This study indicates that leucofiltration can prevent the formation of leucocyte- and platelet-derived microparticles, and might reduce haemolysis in irradiated whole blood, either by removing factors that provoke haemolysis, or by selective retention of senescent or effete red cells most prone to haemolysis.

Preoperative autologous blood donation: clinical, economic, and ethical issues.

PubMed

Domen, R E

1996-09-01

Many patients are donating their own blood before surgery to avoid blood-borne infections, often on the advice of their physicians. But autologous blood transfusion, while safer than allogeneic transfusion, is not completely risk-free. It is also expensive, its benefits are difficult to assess, and its increasing popularity raises many difficult ethical issues, such as whether the benefit of allogeneic transfusion supports its additional expense. Record-keeping, collection, and transfusion errors are occasional risks of autologous transfusions. In addition, risks associated with blood donation, from mild dizziness to precipitation of angina, should be considered when high-risk patients are referred for autologous collection. Only approximately half of autologous units collected are actually used, and the cost per quality-adjusted year of life saved may be as high as $1 million, depending on the type of surgical procedure. Although recombinant human erythropoietin can stimulate red blood cell production before autologous donation and decrease the need for transfusion, it is not clear whether this strategy, which can cost thousands of dollars per patient, will be cost-effective. Perioperative hemodilution may become an important component in efforts to reduce patient exposure to allogeneic blood, but its use remains controversial.

In vitro effects of metals on isolated head-kidney and blood leucocytes of the teleost fish Sparus aurata L. and Dicentrarchus labrax L.

PubMed

Morcillo, Patricia; Meseguer, José; Esteban, M Ángeles; Cuesta, Alberto

2016-07-01

The in vitro use of fish leucocytes to test the toxicity of aquatic pollutants, and particularly the immutoxicological effects, could be a valuable alternative to fish bioassays but has received little attention. In this study, head-kidney and peripheral blood leucocytes (HKLs and PBLs, respectively) from gilthead seabream (Sparus aurata L.) and European sea bass (Dicentrarchus labrax L.) specimens were exposed to Cd, MeHg (methylmercury), Pb or As for 24 h being evaluated the resulting cytotoxicity. Exposure to metals produced a dose-dependent reduction in the viability, and MeHg showed the highest toxicity followed by Cd, As and Pb. Interestingly, leucocytes from European sea bass are more resistant to metal exposure than those from gilthead seabream. Similarly, HKLs are always more sensitive than those isolated from blood from the same fish species. Moreover, fish leucocytes incubated with metals exhibited alterations in gene expression profiles that were more pronounced in the HKLs in general, being Pb the metal provoking less effects. Concretely, genes related to cellular protection (metallothionein), stress (heat shock protein 70) and oxidative stress (superoxide dismutase, catalase and glutathione reductase) were, in general, down-regulated in seabream HKLs but up-regulated in seabream PBLs and sea bass HKLs and PBLs. In addition, this profile leads to the increase of expression in genes related to apoptosis (Bcl2 associated X protein and caspase 3). Finally, transcription of genes involved in immunity (interleukin-1β and immunoglobulin M) was down-regulated, mainly in seabream leucocytes. This study points to the benefits for evaluating the toxicological mechanisms of marine pollution using fish leucocytes in vitro and insight into the mechanisms at gene level. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical-scale laser-based scanning and processing of live cells: selective photothermal killing of fluorescent tumor targets for autologous stem cell transplantation

NASA Astrophysics Data System (ADS)

Koller, Manfred R.; Hanania, Elie G.; Eisfeld, Timothy; O'Neal, Robert A.; Khovananth, Kevin M.; Palsson, Bernhard O.

2001-04-01

High-dose chemotherapy, followed by autologous hematopoietic stem cell (HSC) transplantation, is widely used for the treatment of cancer. However, contaminating tumor cells within HSC harvests continue to be of major concern since re-infused tumor cells have proven to contribute to disease relapse. Many tumor purging methods have been evaluated, but all leave detectable tumor cells in the transplant and result in significant loss of HSCs. These shortcomings cause engraftment delays and compromise the therapeutic value of purging. A novel approach integrating automated scanning cytometry, image analysis, and selective laser-induced killing of labeled cells within a cell mixture is described here. Non-Hodgkin's lymphoma (NHL) cells were spiked into cell mixtures, and fluorochrome-conjugated antibodies were used to label tumor cells within the mixture. Cells were then allowed to settle on a surface, and as the surface was scanned with a fluorescence excitation source, a laser pulse was fired at every detected tumor cell using high-speed beam steering mirrors. Tumor cells were selectively killed with little effect on adjacent non-target cells, demonstrating the feasibility of this automated cell processing approach. This technology has many potential research and clinical applications, one example of which is tumor cell purging for autologous HSC transplantation.

Avian leucocyte counting using the hemocytometer

USGS Publications Warehouse

Dein, F.J.; Wilson, A.; Fischer, D.; Langenberg, P.

1994-01-01

Automated methods for counting leucocytes in avian blood are not available because of the presence of nucleated erythrocytes and thrombocytes. Therefore, total white blood cell counts are performed by hand using a hemocytometer. The Natt and Herrick and the Unopette methods are the most common stain and diluent preparations for this procedure. Replicate hemocytometer counts using these two methods were performed on blood from four birds of different species. Cells present in each square of the hemocytometer were counted. Counting cells in the corner, side, or center hemocytometer squares produced statistically equivalent results; counting four squares per chamber provided a result similar to that obtained by counting nine squares; and the Unopette method was more precise for hemocytometer counting than was the Natt and Herrick method. The Unopette method is easier to learn and perform but is an indirect process, utilizing the differential count from a stained smear. The Natt and Herrick method is a direct total count, but cell identification is more difficult.

Combined use of decellularized allogeneic artery conduits with autologous transdifferentiated adipose-derived stem cells for facial nerve regeneration in rats.

PubMed

Sun, Fei; Zhou, Ke; Mi, Wen-juan; Qiu, Jian-hua

2011-11-01

Natural biological conduits containing seed cells have been widely used as an alternative strategy for nerve gap reconstruction to replace traditional nerve autograft techniques. The purpose of this study was to investigate the effects of a decellularized allogeneic artery conduit containing autologous transdifferentiated adipose-derived stem cells (dADSCs) on an 8-mm facial nerve branch lesion in a rat model. After 8 weeks, functional evaluation of vibrissae movements and electrophysiological assessment, retrograde labeling of facial motoneurons and morphological analysis of regenerated nerves were performed to assess nerve regeneration. The transected nerves reconstructed with dADSC-seeded artery conduits achieved satisfying regenerative outcomes associated with morphological and functional improvements which approached those achieved with Schwann cell (SC)-seeded artery conduits, and superior to those achieved with artery conduits alone or ADSC-seeded artery conduits, but inferior to those achieved with nerve autografts. Besides, numerous transplanted PKH26-labeled dADSCs maintained their acquired SC-phenotype and myelin sheath-forming capacity inside decellularized artery conduits and were involved in the process of axonal regeneration and remyelination. Collectively, our combined use of decellularized allogeneic artery conduits with autologous dADSCs certainly showed beneficial effects on nerve regeneration and functional restoration, and thus represents an alternative approach for the reconstruction of peripheral facial nerve defects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Using urinary leucocyte esterase tests as an indicator of infection with gonorrhoea or chlamydia in asymptomatic males in a primary health care setting.

PubMed

Rahman, Md Saifur; Beever, Warwick; Skov, Steven; Boffa, John

2014-02-01

To evaluate a leucocyte esterase test as a predictor of gonorrhoea or chlamydia in asymptomatic Aboriginal males at the Central Australian Aboriginal Congress Male Clinic (Ingkintja), first-void urine samples and clinical information were collected from consecutive asymptomatic males presenting to the Ingkintja in Alice Springs between March 2008 and December 2009. Urine was tested immediately with a leucocyte esterase test dipstick and then by polymerase chain reaction for gonorrhoea and chlamydia. Among the 292 specimens from asymptomatic males, 15.4% were positive for gonorrhoea or chlamydia. In this group, compared with polymerase chain reaction result for gonorrhoea or chlamydia, leucocyte esterase test alone and in combination with age ≤35 years showed sensitivities of 66.7% and 60%, specificities of 90.7% and 94.7%, positive predictive values of 56.6% and 67.5%, negative predictive values of 93.7% and 92.8% and the area under receiver operating characteristics curve values of 0.79 and 0.85, respectively. Leucocyte esterase tests can reasonably be used as a basis for immediate empirical treatment for gonorrhoea or chlamydia in asymptomatic central Australian Aboriginal men under 35 years of age.

Autologous bone marrow purging with LAK cells.

PubMed

Giuliodori, L; Moretti, L; Stramigioli, S; Luchetti, F; Annibali, G M; Baldi, A

1993-12-01

In this study we will demonstrate that LAK cells, in vitro, can lyse hematologic neoplastic cells with a minor toxicity of the staminal autologous marrow cells. In fact, after bone marrow and LAK co-culture at a ratio of 1/1 for 8 hours, the inhibition on the GEMM colonies resulted to be 20% less compared to the untreated marrow. These data made LAK an inviting agent for marrow purging in autologous bone marrow transplantation.

Characterization of swine leucocyte antigen alleles in a crossbred pig to be used in xenotransplant studies.

PubMed

Reyes, L M; Blosser, R J; Smith, R F; Miner, A C; Paris, L L; Blankenship, R L; Tector, M F; Tector, A J

2014-11-01

We have characterized swine leucocyte antigen (SLA) classes I and II molecules of a domestic pig as a model for use in our xenotransplant program. Molecular characterization of the SLA classes I and II genes is critical to understanding the adaptive immune responses between swine and humans in the event of xenotransplantation. Seven swine leucocyte antigen genes (SLA-1, SLA-2, SLA-3, DQB1, DRB1, DQA and DRA) were analyzed and 15 alleles were identified. A novel DRA*w04re01 is reported for this limited polymorphic class II gene. The heterozygous haplotypes, Hp-32.0/35.0 and Hp-0.13/0.23 were deduced for our IU-pig model, for SLA classes I and II regions, respectively. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of autologous blood cell therapies

PubMed Central

Kim, Ah Ram; Sankaran, Vijay G.

2016-01-01

Allogeneic hematopoietic stem cell transplantation and blood cell transfusions are commonly performed in patients with a variety of blood disorders. Unfortunately, these donor-derived cell therapies are constrained due to limited supplies, infectious risk factors, a lack of appropriately matched donors, and the risk of immunologic complications from such products. The use of autologous cell therapies has been proposed to overcome these shortcomings. One can derive such therapies directly from hematopoietic stem and progenitor cells of individuals, which can then be manipulated ex vivo to produce desired modifications or differentiated to produce a particular target population. Alternatively, pluripotent stem cells, which have a theoretically unlimited self-renewal capacity and an ability to differentiate into any desired cell type, can be used as an autologous starting source for such manipulation and differentiation approaches. In addition, such cell products can also be used as a delivery vehicle for therapeutics. In this review, we highlight recent advances and discuss ongoing challenges for the in vitro generation of autologous hematopoietic cells that can be used for cell therapy. PMID:27345108

Characterization of binding specificities of Bovine Leucocyte class I molecules: Impacts for rational epitope discovery

USDA-ARS?s Scientific Manuscript database

The binding of peptides to classical major histocompatibility complex (MHC) class-I proteins is the single most selective step in antigen presentation. However, the peptide binding specificity of cattle MHC (bovine leucocyte antigen, BoLA) class I (BoLA-I) molecules remains poorly characterized. Her...

Autologous buccal mucosa graft augmentation for foreshortened vagina.

PubMed

Grimsby, Gwen M; Bradshaw, Karen; Baker, Linda A

2014-05-01

Vaginal foreshortening after pelvic surgery or radiotherapy may lead to dyspareunia and decreased quality of life. Unfortunately, little literature exists regarding treatment options for this debilitating problem. Autologous buccal mucosal grafting has been previously reported for creation of a total neovagina and the repair of postvaginoplasty vaginal stenosis. Autologous buccal mucosa offers several advantages as a replacement material for vaginal reconstruction. Vaginal and oral buccal mucosa are both hairless, moist, nonkeratinized stratified squamous epithelia. Buccal mucosa has a dense layer of elastic fibers, imparting both elasticity and strength, and acquires a robust neovascularity with excellent graft take. The graft material is readily available and donor site scars are hidden in the mouth. A 60-year-old woman had vaginal foreshortening to 4.5 cm 15 years after radical hysterectomy and brachytherapy for endometrial cancer. She was unable to have intercourse despite attempted vaginal dilation. Her foreshortened vagina was successfully augmented with autologous buccal mucosa grafting at the apex, increasing her vaginal length to 8 cm and permitting pain-free intercourse. Even in the face of an altered surgical field after radical hysterectomy and radiation, autologous buccal mucosa is an option for vaginal reconstruction for vaginal foreshortening.

Mechanical and chemical characteristics of an autologous glue.

PubMed

De Somer, Filip; Delanghe, Joris; Somers, Pamela; Debrouwere, Maarten; Van Nooten, Guido

2008-09-15

The study evaluates the mechanical and chemical characteristics of autologous surgical glue made by mixing ultrafiltered plasma with glutaraldehyde (GTA). Human albumin 200 g/L mixed with different concentrations of GTA (25, 50, 75, or 100 g/L) was used as a single protein set-up for testing tensile strength, elasticity, and rate of crosslinking. Subsequently, ultrafiltered canine or human plasma to obtain autologous glue replaced human albumin. BioGlue, a surgical glue, and Tissucol Duo, a fibrin sealant, were used as controls. Tensile strength of human albumin 200 g/L mixed with 75 g/L GTA is 825 +/- 109 N versus 672 +/- 167 N for BioGlue. Ultrafiltered canine plasma showed a maximum tensile strength of 634 +/- 137 N when mixed with GTA 75 g/L. For human plasma, the maximum tensile strength of 436 +/- 69 N was reached after mixing with GTA 25 g/L. Autologous glue had a higher elasticity of 144 +/- 66 N versus 322 +/- 104 N for BioGlue at maximum load. Autologous glues for vascular repair can be easily prepared out of the patient's plasma. The optimal characteristics, compared to BioGlue, are obtained for ultrafiltered canine and human plasma by mixing with a GTA concentration of 50-75 g/L and 25-50 g/L, respectively. The autologous glue will exert less tensile strength than BioGlue but has a better compliance. In case where no plasma can obtained from the patient, mixing human albumin 200 g/L with GTA 75 g/L can be an alternative to BioGlue.

Autologous patch graft in tube shunt surgery.

PubMed

Aslanides, I M; Spaeth, G L; Schmidt, C M; Lanzl, I M; Gandham, S B

1999-10-01

To evaluate an alternate method of covering the subconjunctival portion of the tube in aqueous shunt surgery. Evidence of tube erosion, graft-related infection, graft melting, or other associated intraocular complications were evaluated. A retrospective study of 16 patients (17 eyes) who underwent tube shunt surgery at Wills Eye Hospital between July 1991 and October 1996 was conducted. An autologous either "free" or "rotating" scleral lamellar graft was created to cover the subconjunctival portion of the tube shunt. All patients were evaluated for at least 6 months, with a mean follow-up of 14.8 months (range 6-62 months). All eyes tolerated the autologous graft well, with no clinical evidence of tube erosion, or graft-related or intraocular complications. Autologous patch graft in tube shunt surgery appears--in selected cases--to be an effective, safe and inexpensive surgical alternative to allogenic graft materials. It also offers ease of availability, and eliminates the risk of transmitting infectious disease.

Cryopreservation of Autologous Blood (Red Blood Cells, Platelets and Plasma)

NASA Astrophysics Data System (ADS)

Ebine, Kunio

Prevention of post-transfusion hepatitis is still a problem in cardiovascular surgery. We initiated the cryopreservation of autologous blood for the transfusion in elective cardiovascular surgery since 1981. This study includes 152 surgical cases in which autologous frozen, allogeneic frozen, and/or allogeneic non-frozen blood were used. In the 152 surgical cases, there were 69 cases in which autologous blood only (Group I) was used; 12 cases with autologous and allogeneic frozen blood (Group II); 46 cases with autologous and allgeneic frozen plus allogeneic non-frozen blood (Group III); and 25 cases with allogeneic frozen plus allogeneic non-frozen blood (Group IV). No hepatitis developed in Groups I (0%) and II (0%), but there was positive hepatitis in Groups III (4.3%) and IV (8.0%) . In 357 cases of those who underwent surgery with allogeneic non-frozen whole blood during the same period, the incidence rate of hepatitis was 13.7% (49/357). Patients awaiting elective surgery can store their own blood in the frozen state. Patients who undergo surgery with the cryoautotransfusion will not produce any infections or immunologic reactions as opposed to those who undergo surgery with the allogeneic non-frozen blood.

Alternative RNA splicing of leucocyte tissue transglutaminase in coeliac disease.

PubMed

Arbildi, P; Sóñora, C; Del Río, N; Marqués, J M; Hernández, A

2018-05-01

Tissue transglutaminase is a ubiquitous and multifunctional protein that contributes to several processes such as apoptosis/survival, efferocytosis, inflammation and tissue repairing under physiological and pathological conditions. Several activities can be associated with well-established functional domains; in addition, four RNA alternative splice variants have been described, characterized by sequence divergences and residues deletion at the C-terminal domains. Tissue transglutaminase is recognized as the central player in the physiopathology of coeliac disease (CD) mainly through calcium-dependent enzymatic activities. It can be hypothesized that differential regulation of tissue transglutaminase splice variants expression in persons with CD contributes to pathology by altering the protein functionality. We characterized the expression pattern of RNA alternative splice variants by RT-PCR in peripheral cells from patients with CD under free gluten diet adhesion; we considered inflammatory parameters and specific antibodies as markers of the stage of disease. We found significant higher expression of both the full length and the shortest C-truncated splice variants in leucocytes from patients with CD in comparison with healthy individuals. As tissue transglutaminase expression and canonical enzymatic activity are linked to inflammation, we studied the RNA expression of inflammatory cytokines in peripheral leucocytes of persons with CD in relation with splice variants expression; interestingly, we found that recently diagnosed patients showed significant correlation between both the full length and the shortest alternative spliced variants with IL-1 expression. Our results points that regulation of alternative splicing of tissue transglutaminase could account for the complex physiopathology of CD. © 2018 The Foundation for the Scandinavian Journal of Immunology.

Development of autologous blood cell therapies.

PubMed

Kim, Ah Ram; Sankaran, Vijay G

2016-10-01

Allogeneic hematopoietic stem cell transplantation and blood cell transfusions are performed commonly in patients with a variety of blood disorders. Unfortunately, these donor-derived cell therapies are constrained due to limited supplies, infectious risk factors, a lack of appropriately matched donors, and the risk of immunologic complications from such products. The use of autologous cell therapies has been proposed to overcome these shortcomings. One can derive such therapies directly from hematopoietic stem and progenitor cells of individuals, which can then be manipulated ex vivo to produce the desired modifications or differentiated to produce a particular target population. Alternatively, pluripotent stem cells, which have a theoretically unlimited self-renewal capacity and an ability to differentiate into any desired cell type, can be used as an autologous starting source for such manipulation and differentiation approaches. Such cell products can also be used as a delivery vehicle for therapeutics. In this review, we highlight recent advances and discuss ongoing challenges for the in vitro generation of autologous hematopoietic cells that can be used for cell therapy. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

The melanocortin MC1 receptor agonist BMS-470539 inhibits leucocyte trafficking in the inflamed vasculature

PubMed Central

Leoni, G; Voisin, M-B; Carlson, K; Getting, SJ; Nourshargh, S; Perretti, M

2010-01-01

Background and purpose: Over three decades of research evaluating the biology of melanocortin (MC) hormones and synthetic peptides, activation of the MC type 1 (MC1) receptor has been identified as a viable target for the development of novel anti-inflammatory therapeutic agents. Here, we have tested a recently described selective agonist of MC1 receptors, BMS-470539, on leucocyte/post-capillary venule interactions in murine microvascular beds. Experimental approach: Intravital microscopy of two murine microcirculations were utilized, applying two distinct modes of promoting inflammation. The specificity of the effects of BMS-470539 was assessed using mice bearing mutant inactive MC1 receptors (the recessive yellow e/e colony). Key results: BMS-470539, given before an ischaemia–reperfusion protocol, inhibited cell adhesion and emigration with no effect on cell rolling, as assessed 90 min into the reperfusion phase. These properties were paralleled by inhibition of tissue expression of both CXCL1 and CCL2. Confocal investigations of inflamed post-capillary venules revealed immunostaining for MC1 receptors on adherent and emigrated leucocytes. Congruently, the anti-inflammatory properties of BMS-470539 were lost in mesenteries of mice bearing the inactive mutant MC1 receptors. Therapeutic administration of BMS-470539 stopped cell emigration, but did not affect cell adhesion in the cremasteric microcirculation inflamed by superfusion with platelet-activating factor. Conclusions and implications: Activation of MC1 receptors inhibited leucocyte adhesion and emigration. Development of new chemical entities directed at MC1 receptors could be a viable approach in the development of novel anti-inflammatory therapeutic agents with potential application to post-ischaemic conditions. PMID:20331604

Autologous chondrocyte implantation: superior biologic properties of hyaline cartilage repairs.

PubMed

Henderson, Ian; Lavigne, Patrick; Valenzuela, Herminio; Oakes, Barry

2007-02-01

Information regarding the quality of autologous chondrocyte implantation repair is needed to determine whether the current autologous chondrocyte implantation surgical technology and the subsequent biologic repair processes are capable of reliably forming durable hyaline or hyaline-like cartilage in vivo. We report and analyze the properties and qualities of autologous chondrocyte implantation repairs. We evaluated 66 autologous chondrocyte implantation repairs in 57 patients, 55 of whom had histology, indentometry, and International Cartilage Repair Society repair scoring at reoperation for mechanical symptoms or pain. International Knee Documentation Committee scores were used to address clinical outcome. Maximum stiffness, normalized stiffness, and International Cartilage Repair Society repair scoring were higher for hyaline articular cartilage repairs compared with fibrocartilage, with no difference in clinical outcome. Reoperations revealed 32 macroscopically abnormal repairs (Group B) and 23 knees with normal-looking repairs in which symptoms leading to arthroscopy were accounted for by other joint disorders (Group A). In Group A, 65% of repairs were either hyaline or hyaline-like cartilage compared with 28% in Group B. Autologous chondrocyte repairs composed of fibrocartilage showed more morphologic abnormalities and became symptomatic earlier than hyaline or hyaline-like cartilage repairs. The hyaline articular cartilage repairs had biomechanical properties comparable to surrounding cartilage and superior to those associated with fibrocartilage repairs.

What is the role of autologous blood transfusion in major spine surgery?

PubMed

Kumar, Naresh; Chen, Yongsheng; Nath, Chinmoy; Liu, Eugene Hern Choon

2012-06-01

Major spine surgery is associated with significant blood loss, which has numerous complications. Blood loss is therefore an important concern when undertaking any major spine surgery. Blood loss can be addressed by reducing intraoperative blood loss and replenishing perioperative blood loss. Reducing intraoperative blood loss helps maintain hemodynamic equilibrium and provides a clearer operative field during surgery. Homologous blood transfusion is still the mainstay for replenishing blood loss in major spine surgery across the world, despite its known adverse effects. These significant adverse effects can be seen in up to 20% of patients. Autologous blood transfusion avoids the risks associated with homologous blood transfusion and has been shown to be cost-effective. This article reviews the different methods of autologous transfusion and focuses on the use of intraoperative cell salvage in major spine surgery. Autologous blood transfusion is a proven alternative to homologous transfusion in major spine surgery, avoiding most, if not all of these adverse effects. However, autologous blood transfusion rates in major spine surgery remain low across the world. Autologous blood transfusion may obviate the need for homologous transfusion completely. We encourage spine surgeons to consider autologous blood transfusion wherever feasible.

Interference of blood leucocytes in the measurements of immature red cells (reticulocytes) by two different (semi-) automated flow-cytometry technologies.

PubMed

Villamor, N; Kirsch, A; Huhn, D; Vives-Corrons, J L; Serke, S

1996-06-01

Flow cytometrical methods have been introduced recently as an alternative to the enumeration of reticulocytes by microscopy. Two of these methods have gained widespread use in haematological practice; the multiparametric flow cytometer using thiazole orange staining (Retic-Count, FACScan) and the single-application reticulocyte counter using auramine-O staining (R-series, Sysmex). Several studies have emphasized the excellent correlations between microscopy and these techniques. The purpose of our study has been to examine the specificity of these automated devices with regard to cells classified as 'reticulocytes' and the effect that this may have on measures of reticulocyte maturity. Our results indicate that the specificity of reticulocyte measurements by both the Sysmex R-1000/-3000 and the Retic-Count system is relatively low. This is due to the presence of leucocytes amongst cells classified as reticulocytes. These leucocytes display intense staining with either dye, leading to an erroneous estimation of RMI (thiazole orange) and high fluorescence count (R-1000/-3000). This error is directly correlated with the leucocyte count. The basis for reticulocyte identification should be improved before automated estimation of reticulocyte maturation can be used in clinical practice.

Regeneration of Tissues and Organs Using Autologous Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anthony Atala

The Joint Commission for Health Care Organizations recently declared the shortage of transplantable organs and tissues a public health crisis. As such, there is about one death every 30 seconds due to organ failure. Complications and rejection are still significant albeit underappreciated problems. It is often overlooked that organ transplantation results in the patient being placed on an immune suppression regimen that will ultimate shorten their life span. Patients facing reconstruction often find that surgery is difficult or impossible due to the shortage of healthy autologous tissue. In many cases, autografting is a compromise between the condition and the curemore » that can result in substantial diminution of quality of life. The national cost of caring for persons who might benefit from engineered tissues or organs has reached $600 billion annually. Autologous tissue technologies have been developed as an alternative to transplantation or reconstructive surgery. Autologous tissues derived from the patient's own cells are capable of correcting numerous pathologies and injuries. The use of autologous cells eliminates the risks of rejection and immunological reactions, drastically reduces the time that patients must wait for lifesaving surgery, and negates the need for autologous tissue harvest, thereby eliminating the associated morbidities. In fact, the use of autologous tissues to create functional organs is one of the most important and groundbreaking steps ever taken in medicine. Although the basic premise of creating tissues in the laboratory has progressed dramatically, only a limited number of tissue developments have reached the patients to date. This is due, in part, to the several major technological challenges that require solutions. To that end, we have been in pursuit of more efficient ways to expand cells in vitro, methods to improve vascular support so that relevant volumes of engineered tissues can be grown, and constructs that can mimic the

Comparison of corticosteroid, autologous blood or sclerosant injections for chronic tennis elbow.

PubMed

Branson, R; Naidu, K; du Toit, C; Rotstein, A H; Kiss, R; McMillan, D; Fooks, L; Coombes, B K; Vicenzino, B

2017-06-01

To compare three different ultrasound-guided injections for chronic tennis elbow. Assessor-blinded, randomized controlled comparative trial. 44 patients with clinically diagnosed tennis elbow, confirmed by Doppler ultrasound, received under ultrasound guidance, a single corticosteroid injection (n=14), or two injections (separated by 4 weeks) of either autologous blood (n=14) or polidocanol (n=16). Clinical and ultrasound examination was performed at baseline, 4, 12 and 26 weeks. Complete recovery or much improvement was greater for corticosteroid injection than autologous blood and polidocanol at 4 weeks (p<0.001, number needed to treat 1 (95% CI 1-2)). In contrast, at 26 weeks corticosteroid was significantly worse than polidocanol (p=0.004, number needed to harm 2 (1-6)). Recurrence after corticosteroid injection was significantly higher than autologous blood or polidocanol (p=0.007, number needed to harm 2 (1-4)). Corticosteroid injection produced greater reduction in tendon thickness and vascularity than autologous blood at 4 weeks only. Compared to autologous blood, polidocanol reduced tendon thickness at 4 and 12 weeks and reduced echogenicity and hyperaemia after 12 or 26 weeks respectively. Injections of corticosteroid cannot be recommended over polidocanol or autologous blood, because despite beneficial short-term effect there were inferior long-term effects. Whether polidocanol or autologous blood injections are effective is unknown, especially as their global effect profiles are not unlike previously reported for wait-and-see. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Detection of occult abscesses with /sup 111/In-labeled leukocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, W.R.; Gurevich, N.; Goris, M.L.

1979-07-01

Clinicians are frequently faced with the problem of a patient in whom they suspect an occult abscess. In such a situation, there may be no clinical signs to localize the site of the abscess and often extensive investigations do not provide additional useful information. This report illustrates the efficacy of autologous leukocytes labeled with /sup 111/In oxine in detecting the site and extent of occult abscesses in two patients. The technique of in vitro lebeling of leukocytes is simple and has been mastered by all of our nuclear medicine technologists.

Autologous blood transfusion in total knee replacement surgery.

PubMed

Sarkanović, Mirka Lukić; Gvozdenović, Ljiljana; Savić, Dragan; Ilić, Miroslav P; Jovanović, Gordana

2013-03-01

Total knee replacement (TKR) surgery is one of the most frequent and the most extensive procedures in orthopedic surgery, accompanied with some serious complications. Perioperative blood loss is one of the most serious losses, so it is vital to recognize and treat such losses properly. Autologous blood transfusion is the only true alternative for the allogeneic blood. The aim of this study was to to examine if autologous blood transfusion reduces usage of allogenic blood in total knee replacement surgery, as well as to examine possible effect of autologous blood transfusion on postoperative complications, recovery and hospital stay of patients after total knee replacement surgery. During the controlled, prospective, randomised study we compared two groups of patients (n = 112) with total prosthesis implanted in their knee. The group I consisted of the patients who received the transfusion of other people's (allogeneic) blood (n = 57) and the group II of the patients whose blood was collected postoperatively and then given them [their own (autologous) blood] (n = 55). The transfusion trigger for both groups was hemoglobin level of 85 g/L. In the group of patients whose blood was collected perioperatively only 9 (0.9%) of the patients received transfusion of allogeneic blood, as opposed to the control group in which 98.24% of the patients received the transfusion of allogeneic blood (p < or = 0.01). The patients whose blood was collected stayed in hospital for 6.18 days, while the patients of the control group stayed 7.67 days (p < 0.01). Autologous blood transfusion is a very effective method for reducing consumption of allogenic blood and thus, indirectly for reducing all complications related to allogenic blood transfusion. There is also a positive influence on postoperative recovery after total knee replacement surgery due to the reduction of hospital stay, and indirectly on the reduction of hospital costs.

Cord Blood Banking Standards: Autologous Versus Altruistic

PubMed Central

Armitage, Sue

2016-01-01

Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as “biological insurance” should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards. PMID:26779485

Effectiveness of autologous serum as an alternative to fetal bovine serum in adipose-derived stem cell engineering.

PubMed

Choi, Jaehoon; Chung, Jee-Hyeok; Kwon, Geun-Yong; Kim, Ki-Wan; Kim, Sukwha; Chang, Hak

2013-09-01

In cell culture, medium supplemented with fetal bovine serum is commonly used, and it is widely known that fetal bovine serum supplies an adequate environment for culture and differentiation of stem cells. Nevertheless, the use of xenogeneic serum can cause several problems. We compared the effects of four different concentrations of autologous serum (1, 2, 5, and 10%) on expansion and adipogenic differentiation of adipose-derived stem cells using 10% fetal bovine serum as a control. The stem cells were grafted on nude mice and the in vivo differentiation capacity was evaluated. The isolation of adipose-derived stem cells was successful irrespective of the culture medium. The proliferation potential was statistically significant at passage 2, as follows: 10% autologous serum > 10% fetal bovine serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. The differentiation capacity appeared statistically significant at passage 4, as follows: 10% fetal bovine serum > 10% autologous serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. Ten percent autologous serum and 10% fetal bovine serum had greater differentiation capacity than 1 and 2% autologous serum in vivo, and no significant difference was observed between the groups at ≥ 5% concentration at 14 weeks. In conclusion, 10% autologous serum was at least as effective as 10% fetal bovine serum with respect to the number of adipose-derived stem cells at the end of both isolation and expansion, whereas 1 and 2% autologous serum was inferior.

Correcting Nasojugal Groove with Autologous Cultured Fibroblast Injection: A Pilot Study.

PubMed

Moon, Kyung-Chul; Lee, Hyun-Su; Han, Seung-Kyu; Chung, Ho-Yun

2018-06-01

A new commercial drug that contains autologous cultured fibroblasts has been developed and approved by the United States Food and Drug Administration for improving the appearance of nasolabial folds. However, the treatment requires three sessions every 3-6 weeks. It is known that the skin overlying the nasojugal groove is thinner, and the wrinkle is generally shallower than nasolabial folds. Therefore, we hypothesized that the nasojugal groove could be improved by just one treatment session. Therefore, the purpose of this study was to evaluate the efficacy and safety of autologous cultured fibroblast injection to correct nasojugal grooves. Forty-six subjects with nasojugal grooves were enrolled in this study. They were injected with autologous cultured fibroblasts or placebo in one session. Blinded evaluators and subjects assessed the efficacy using a validated wrinkle assessment scale at 4, 12, and 24 weeks after the injection. Information of adverse events was collected at each visit. Based on the evaluators' assessment at 24 weeks after the injection, 76% of subjects treated with autologous cultured fibroblasts showed improvement whereas 0% of subjects treated with placebo showed improvement (P < 0.0001). Based on self-assessment at 24 weeks after the injection, 72% of subjects treated with autologous cultured fibroblasts and 45% of subjects treated with placebo showed improvement (P = 0.0662). There were no serious adverse events related to autologous cultured fibroblast injection. Autologous cultured fibroblast injection might be effective and safe to correct nasojugal grooves. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Thalidomide and prednisolone versus prednisolone alone as consolidation therapy after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the ALLG MM6 multicentre, open-label, randomised phase 3 study.

PubMed

Kalff, Anna; Kennedy, Nola; Smiley, Angela; Prince, H Miles; Roberts, Andrew W; Bradstock, Kenneth; De Abreu Lourenço, Richard; Frampton, Chris; Spencer, Andrew

2014-12-01

We previously showed that consolidation therapy with thalidomide and prednisolone improved progression-free and overall survival in patients with multiple myeloma who had undergone autologous stem-cell transplantation. We aimed to assess whether these survival advantages were durable at 5 years. The ALLG MM6 trial was a multicentre, open-label, randomised phase 3 trial done between Jan 13, 2002, and March 15, 2005, at 29 sites in Australia and New Zealand. Patients with newly diagnosed multiple myeloma were randomly assigned (1:1), via computer-generated randomisation charts, to receive indefinite prednisolone maintenance alone (control group) or in combination with 12 months of thalidomide consolidation (thalidomide group) after autologous stem-cell transplantation. Randomisation was stratified by treating centre and pre-transplantation concentrations of β2 microglobulin. Patients and treating physicians were not masked to treatment allocation. Primary endpoints were progression-free survival and overall survival. Analysis was by intention to treat. Secondary endpoints were overall response to salvage therapy, incidence of second primary malignancy incidence, and cost-effectiveness. This trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12607000382471. We randomly assigned 269 patients to the thalidomide (n=114) or control group (n=129). After a median follow-up of 5·4 years (IQR 3·1-7·2), estimated 5-year progression-free survival was 27% (95% CI 23-32) in the thalidomide group and 15% (11-18) in the control group (hazard ratio [HR] 0·16, 95% CI 0·044-0·58; p=0·0054) and 5-year overall survival was 66% (95% CI 61-70) and 47% (42-51), respectively (HR 0·12, 95% CI 0·028-0·56; p=0·0072). There was no difference in overall response to salvage therapy, survival post-progression, or incidence of secondary malignancies between the two groups. Incremental cost-effectiveness ratio was AUS$26 996 per mean life

Autologous Blood Versus Fibrin Glue in Pterygium Excision With Conjunctival Autograft Surgery.

PubMed

Nadarajah, Gaayathri; Ratnalingam, Vanitha Hema; Mohd Isa, Hazlita

2017-04-01

To evaluate graft stability and recurrence rate between fibrin glue and autologous blood in pterygium conjunctival autograft surgery. A prospective, randomized, single-blinded clinical trial to assess the efficacy of autologous blood in place of fibrin glue in pterygium surgery. A total of 120 eyes of 111 patients were randomized according to pterygium morphology, to undergo pterygium surgery with autografting using either autologous blood or fibrin glue. All patients were operated by a single surgeon; 58 eyes were operated using fibrin glue and 62 eyes had a conjunctival autograft with autologous blood. Patients were seen on postoperative day 1, 1 week, 1 month, 6 months, and 1 year after surgery. Graft stability and pterygium recurrence were graded by an independent observer who was masked to the method of treatment. All 120 eyes completed the 1-year follow-up. Graft loss was seen only in the autologous blood group. Of the 62 eyes in this group, a total of 15 (24.2%) grafts dislodged. Recurrence was calculated after excluding grafts that were dislodged. Of the 105 patients, there were a total of 7 recurrences, 2 (3.4%) from the fibrin adhesive method and 5 (10.6%) from the autologous blood method. This was not statistically significant (P = 0.238). Autologous blood does not exhibit similar graft stability seen with fibrin glue. Although the recurrence rate may not be significant, careful patient selection and a standard method needs to be laid out before the use of this method is widely accepted.

Efficacy of autologous platelets in macular hole surgery.

PubMed

Konstantinidis, Aristeidis; Hero, Mark; Nanos, Panagiotis; Panos, Georgios D

2013-01-01

The introduction of optical coherence tomography has allowed accurate measurement of the size of macular holes. A retrospective consecutive review was performed of 21 patients undergoing macular hole repair with vitrectomy, gas tamponade, and autologous platelet injection and we assessed the effect of macular hole parameters on anatomic and functional outcomes. We looked at the demographic features, final visual outcome, and anatomical closure. Twenty-one patients were included in the study. They underwent routine vitrectomy with gas tamponade (C3F8) and injection of autologous platelets. All patients were advised to maintain a facedown posture for 2 weeks. Anatomical closure was confirmed in all cases and 20 out of 21 of patients had improved postoperative visual acuity by two or more lines. In our series, the macular hole dimensions did not have much effect on the final results. The use of autologous platelets and strict facedown posture seems to be the deciding factor in good anatomical and visual outcome irrespective of macular hole dimensions.

The Potent Humanin Analogue (HNG) Protects Germ Cells and Leucocytes While Enhancing Chemotherapy-Induced Suppression of Cancer Metastases in Male Mice.

PubMed

Lue, YanHe; Swerdloff, Ronald; Wan, Junxiang; Xiao, Jialin; French, Samuel; Atienza, Vince; Canela, Victor; Bruhn, Kevin W; Stone, Brian; Jia, Yue; Cohen, Pinchas; Wang, Christina

2015-12-01

Humanin is a peptide that is cytoprotective against stresses in many cell types. We investigated whether a potent humanin analogue S14G-humanin (HNG) would protect against chemotherapy-induced damage to normal cells without interfering with the chemotherapy-induced suppression of cancer cells. Young adult male mice were inoculated iv with murine melanoma cells. After 1 week, cancer-bearing mice were randomized to receive either: no treatment, daily ip injection of HNG, a single ip injection of cyclophosphamide (CP), or CP+HNG and killed at the end of 3 weeks. HNG rescued the CP-induced suppression of leucocytes and protected germ cell from CP-induced apoptosis. Lung metastases were suppressed by HNG or CP alone, and further suppressed by CP+HNG treatment. Plasma IGF-1 levels were suppressed by HNG with or without CP treatment. To investigate whether HNG maintains its protective effects on spermatogonial stem cells, sperm output, and peripheral leucocytes after repeated doses of CP, normal adult male mice received: no treatment, daily sc injection of HNG, 6 ip injections of CP at 5-day intervals, and the same regimens of CP+HNG and killed at the end of 4 weeks of treatment. Cauda epididymal sperm counts were elevated by HNG and suppressed by CP. HNG rescued the CP-induced suppression of spermatogonial stem cells, sperm count and peripheral leucocytes. We conclude that HNG 1) protects CP-induced loss of male germ cells and leucocytes, 2) enhances CP-induced suppression of cancer metastases, and 3) acts as a caloric-restriction mimetic by suppressing IGF-1 levels. Our findings suggest that humanin analogues may be promising adjuvants to chemotherapy.

The Potent Humanin Analogue (HNG) Protects Germ Cells and Leucocytes While Enhancing Chemotherapy-Induced Suppression of Cancer Metastases in Male Mice

PubMed Central

Lue, YanHe; Swerdloff, Ronald; Wan, Junxiang; Xiao, Jialin; French, Samuel; Atienza, Vince; Canela, Victor; Bruhn, Kevin W.; Stone, Brian; Jia, Yue; Cohen, Pinchas

2015-01-01

Humanin is a peptide that is cytoprotective against stresses in many cell types. We investigated whether a potent humanin analogue S14G-humanin (HNG) would protect against chemotherapy-induced damage to normal cells without interfering with the chemotherapy-induced suppression of cancer cells. Young adult male mice were inoculated iv with murine melanoma cells. After 1 week, cancer-bearing mice were randomized to receive either: no treatment, daily ip injection of HNG, a single ip injection of cyclophosphamide (CP), or CP+HNG and killed at the end of 3 weeks. HNG rescued the CP-induced suppression of leucocytes and protected germ cell from CP-induced apoptosis. Lung metastases were suppressed by HNG or CP alone, and further suppressed by CP+HNG treatment. Plasma IGF-1 levels were suppressed by HNG with or without CP treatment. To investigate whether HNG maintains its protective effects on spermatogonial stem cells, sperm output, and peripheral leucocytes after repeated doses of CP, normal adult male mice received: no treatment, daily sc injection of HNG, 6 ip injections of CP at 5-day intervals, and the same regimens of CP+HNG and killed at the end of 4 weeks of treatment. Cauda epididymal sperm counts were elevated by HNG and suppressed by CP. HNG rescued the CP-induced suppression of spermatogonial stem cells, sperm count and peripheral leucocytes. We conclude that HNG 1) protects CP-induced loss of male germ cells and leucocytes, 2) enhances CP-induced suppression of cancer metastases, and 3) acts as a caloric-restriction mimetic by suppressing IGF-1 levels. Our findings suggest that humanin analogues may be promising adjuvants to chemotherapy. PMID:26384090

Type I allergic hypersensitivity reactions due to ethylene oxide sterilised leucocyte filters in patients with thalassaemia: report of four cases.

PubMed

Belen, Burcu; Polat, Meltem

2015-02-27

Ethylene oxide (EO) is a highly reactive gas used in sterilisation of heat sensitive medical devices, such as infusion sets, cannulae, intubation materials, ventriculoperitoneal shunts, dialysis catheters and stents. Allergic reactions due to EO have been reported in haemodialysis patients, patients undergoing extracorporeal photopheresis and donors of plasmapheresis. Clinical manifestations vary considerably and generally do not allow differentiation between IgE-mediated anaphylaxis and anaphylactoid reactions. We report four patients with thalassaemia who experienced anaphylaxis during transfusion due to ethylene oxide sterilised leucocyte filters. The aim of this report is to highlight the fact that frequently transfused patients can have allergic reactions due to EO particles left in leucocyte filters. 2015 BMJ Publishing Group Ltd.

Perinatal outcomes after gestational surrogacy versus autologous IVF: analysis of national data.

PubMed

Sunkara, Sesh Kamal; Antonisamy, Belavendra; Selliah, Hepsy Y; Kamath, Mohan S

2017-12-01

Anonymized data were obtained from the Human Fertilization and Embryology Authority to determine whether gestational surrogacy influences perinatal outcomes compared with pregnancies after autologous IVF. A total of 103,160 singleton live births, including 244 after gestational surrogacy, 87,571 after autologous fresh IVF and intractyoplasmic sperm injection (ICSI) and 15,345 after autologous frozen embryo transfers were analysed. Perinatal outcomes of pretern birth (PTB), low birth weight (LBW) and high birth weight (HBW) were compared. No difference was found in the risk of PTB and LBW after gestational surrogacy compared with autologous fresh IVF-ICSI: PTB (adjusted OR 0.90, 95% CI 0.56 to 1.42), LBW (adjusted OR 0.90, 95% CI 0.57 to 1.43) and gestational surrogacy compared with autologous frozen embryo transfers: PTB (adjusted OR 0.96, 95% CI 0.58 to 1.60), LBW (adjusted OR 1.16, 95% CI 0.69 to 1.96). The incidence of HBW was significantly higher after gestational surrogacy compared with fresh IVF-ICSI (adjusted OR 1.94, 95% CI 1.38 to 2.75); no difference was found in HBW between gestational surrogacy and autologous frozen embryo transfers. The dataset is limited by lack of information on confounders, i.e. ethnicity, body mass index, underlying medical history, which could result in residual confounding. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

[Autologous epidermal sheets production for skin cellular therapy].

PubMed

Vacher, D

2003-05-01

Cell therapy is becoming a very interesting solution to replace degenerated or damaged tissues. In January 1998, Genevrier Laboratories inaugurated a new department especially designed for the production of cultured cells as therapeutic agents. Meeting clinician therapeutic needs by providing autologous keratinocytes and chondrocytes in the near future, represents the primary aim of the Biotechnology department. Concrete cell-based products are already being used for the treatment of burns and cutaneous chronic wounds such as the EPIBASE graft, which corresponds to an epidermis sheet composed of cultured autologous keratinocytes.

Engraftment of autologous bone marrow cells into the injured cranial cruciate ligament in dogs.

PubMed

Linon, E; Spreng, D; Rytz, U; Forterre, S

2014-12-01

Current research indicates that exogenous stem cells may accelerate reparative processes in joint disease but, no previous studies have evaluated whether bone marrow cells (BMCs) target the injured cranial cruciate ligament (CCL) in dogs. The objective of this study was to investigate engraftment of BMCs following intra-articular injection in dogs with spontaneous CCL injury. Autologous PKH26-labelled BMCs were injected into the stifle joint of eight client-owned dogs with CCL rupture. The effects of PKH26 staining on cell viability and PKH26 fluorescence intensity were analysed in vitro using a MTT assay and flow cytometry. Labelled BMCs in injured CCL tissue were identified using fluorescence microscopy of biopsies harvested 3 and 13 days after intra-articular BMC injection. The intensity of PKH26 fluorescence declines with cell division but was still detectable after 16 days. Labelling with PKH26 had no detectable effect on cell viability or proliferation. Only rare PKH26-positive cells were present in biopsies of the injured CCL in 3/7 dogs and in synovial fluid in 1/7 dogs. No differences in transforming growth factor-β1, and interleukin-6 before and after BMC treatment were found and no clinical complications were noted during a 1 year follow-up period. In conclusion, BMCs were shown to engraft to the injured CCL in dogs when injected into the articular cavity. Intra-articular application of PKH26-labelled cultured mesenchymal stem cells is likely to result in higher numbers of engrafted cells that can be tracked using this method in a clinical setting. Copyright © 2014 Elsevier Ltd. All rights reserved.

Autologous Serum Therapy in Chronic Urticaria

PubMed Central

Patil, Sharmila; Sharma, Nidhi; Godse, Kiran

2013-01-01

Autologous serum therapy is a promising therapy for treatment resistant urticaria. This is useful in developing countries as this is economical option. Minimum instruments like centrifuge, syringe and needles are required for the procedure. PMID:23723475

Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting

PubMed Central

Alexander, Robert W; Harrell, David B

2013-01-01

Objectives Provide background for use of acquiring autologous adipose tissue as a tissue graft and source of adult progenitor cells for use in cosmetic plastic surgery. Discuss the background and mechanisms of action of closed syringe vacuum lipoaspiration, with emphasis on accessing adipose-derived mesenchymal/stromal cells and the stromal vascular fraction (SVF) for use in aesthetic, structural reconstruction and regenerative applications. Explain a proven protocol for acquiring high-quality autologous fat grafts (AFG) with use of disposable, microcannula systems. Design Explain the components and advantage of use of the patented super luer-lock and microcannulas system for use with the closed-syringe system. A sequential explanation of equipment selection for minimally traumatic lipoaspiration in small volumes is presented, including use of blunt injection cannulas to reduce risk of embolism. Results Thousands of AFG have proven safe and efficacious for lipoaspiration techniques for large and small structural fat grafting procedures. The importance and advantages of gentle harvesting of the adipose tissue complex has become very clear in the past 5 years. The closed-syringe system offers a minimally invasive, gentle system with which to mobilize subdermal fat tissues in a suspension form. Resulting total nuclear counting of undifferentiated cells of the adipose-derived -SVF suggests that the yield achieved is better than use of always-on, constant mechanical pump applied vacuum systems. Conclusion Use of a closed-syringe lipoaspiration system featuring disposable microcannulas offers a safe and effective means of harvesting small volumes of nonmanipulated adipose tissues and its accompanying progenitor cells within the SVF. Closed syringes and microcannulas are available as safe, sterile, disposable, compact systems for acquiring high-quality AFG. Presented is a detailed, step-by-step, proven protocol for performing quality autologous structural adipose

Preeclampsia in autologous and oocyte donation pregnancy: is there a different pathophysiology?

PubMed

Lashley, Lisa E E L O; Buurma, Aletta; Swings, Godelieve M J S; Eikmans, Michael; Anholts, Jacqueline D H; Bakker, Jaap A; Claas, Frans H J

2015-06-01

Oocyte donation (OD) is a specific method of artificial reproductive technology that is accompanied by a higher risk of preeclampsia during pregnancy. The pathophysiological mechanism underlying preeclampsia in OD pregnancies is thought to differ from preeclampsia in autologous pregnancies. As preeclampsia in autologous pregnancies is suggested to be associated with complement activation, we studied C4d deposition, circulating complement components and placental complement regulatory proteins in preeclamptic OD pregnancies. Women with uncomplicated and preeclamptic pregnancies after OD or spontaneous conception were selected. We stained the placentas for C4d, marker for complement activation, measured complement factors C1q, C3 and C4 in maternal sera and quantified the placental mRNA expression of complement regulatory proteins CD46, CD55 and CD59. A significantly (p < 0.03) higher incidence of C4d deposition was observed in placentas from women with preeclampsia compared with uncomplicated pregnancies, both OD and autologous. The level of complement factors in serum did not differ between the groups. Children born in the autologous preeclampsia group were significantly lower in birth weight (p < 10th percentile) compared with the preeclamptic OD group. In addition, the placental mRNA expression level of complement regulatory proteins was significantly lower in uncomplicated and preeclamptic OD compared with the autologous pregnancies. In line with autologous preeclampsia pregnancies, there is excessive activation of complement in preeclamptic OD pregnancies. However, in contrast to autologous pregnancies this is not associated with counterbalancing upregulation of complement regulatory proteins. Furthermore, C4d deposition in OD pregnancies is not related to the severity of preeclampsia, suggesting another trigger or regulatory mechanism of placental C4d deposition in preeclamptic OD pregnancies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody Mediated Rejection After Vascularized Composite Allotransplantation

DTIC Science & Technology

2017-10-01

Award Number: W81XWH-16-1-0664 TITLE: Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody-Mediated Rejection after...Annual 3. DATES COVERED 15 Sep 2016 – 14 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Autologous Hematopoietic Stem Cell Transplantation to...sensitization, autologous hematopoietic stem cell transplantation, antibody mediated rejection, donor specific antibodies 16. SECURITY CLASSIFICATION OF

Is Unilateral Implant or Autologous Breast Reconstruction Better in Obtaining Breast Symmetry?

PubMed

Cohen, Oriana; Small, Kevin; Lee, Christina; Petruolo, Oriana; Karp, Nolan; Choi, Mihye

2016-01-01

Unilateral breast reconstruction poses a special set of challenges to the reconstructive breast surgeon compared to bilateral reconstructions. No studies to date provide an objective comparison between autologous and implant based reconstructions in matching the contralateral breast. This study compares the quantitative postoperative results between unilateral implant and autologous flap reconstructions in matching the native breast in shape, size, and projection using three-dimensional (3D) imaging. Sixty-four patients who underwent unilateral mastectomy with tissue expander (TE)-implant (n = 34) or autologous microvascular free transverse rectus abdominus myocutaneous (TRAM; n = 18) or deep inferior epigastric artery perforator (DIEP; n = 12) flap (n = 30) reconstruction from 2007 to 2010 were analyzed. Key patient demographics and risk factors were collected. Using 3D scans of patients obtained during pre and postoperative visits including over 1 year follow-ups for both groups, 3D models were constructed and analyzed for total breast volume, anterior-posterior projection from the chest wall, and 3D comparison. No significant differences in mean age, body mass index, or total number of reconstructive surgeries were observed between the two groups (TE-implant: 52.2 ± 10, 23.9 ± 3.7, 3 ± 0.9; autologous: 50.7 ± 9.4, 25.4 ± 3.9, 2.9 ± 1.3; p > 0.05). The total volume difference between the reconstructed and contralateral breasts in the TE-implant group was insignificant: 27.1 ± 22.2 cc, similar to the autologous group: 29.5 ± 24.7 cc, as was the variance of breast volume from the mean. In both groups, the reconstructed breast had a larger volume. A-P projections were similar between the contralateral and the reconstructed breasts in the TE-implant group: 72.5 ± 3.21 mm versus 71.7 ± 3.5 mm (p > 0.05). The autologous reconstructed breast had statistically insignificant but less A-P projection compared to the contralateral breast (81.9 ± 16.1 mm versus 61

Quantitative and volume, conductivity and scatter changes in leucocytes of patients with acute undifferentiated febrile illness: a pilot study.

PubMed

Kalra, Varun; Ahmad, Sohaib; Shrivastava, Vikas; Mittal, Garima

2016-05-01

A single diagnostic test for acute undifferentiated febrile illnesses (AUFI) is elusive. This pilot study was undertaken on the premise that leucocytes, being the main cells of defence, undergo quantitative, structural and functional changes in AUFI. We evaluated the potential of volume, conductivity and scatter (VCS) parameters of leucocytes, generated with the haemogram report by the Coulter auto-analyzer, in differentiating the common etiologies of AUFI. The haematological and VCS data obtained from 800 controls and 200 cases of AUFI (50 cases each of acute malaria, dengue, scrub typhus and enteric fever) were retrieved for analysis. The cases and controls differed significantly with respect to relative numbers and the VCS parameters of neutrophils, lymphocytes and monocytes (p<0.05). The neutrophil and lymphocyte were significantly voluminous in acute malaria and scrub typhus as compared to dengue and enteric fevers (p<0.05). Enteric fever significantly enhanced the conductivity of neutrophils as compared to other subgroups while lymphocyte conductivity significantly differed from dengue and scrub typhus. Lymphocyte and neutrophil scatter values in malaria and scrub typhus were comparable but differed significantly from that in enteric fever. Etiology-specific changes occur in leucocytes, both in numbers and their VCS properties which can be identified without additional cost. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evaluation of polyethylene glycol coated liposomes labeled with Tc-99m as a blood pool agent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, W.T.; Klipper, R.; Goins, B.

1994-05-01

This investigation evaluated Tc-99m liposomes coated with polyethylene glycol (PEG) as a blood pool agent in comparison with Tc-99m liposomes carrying no surface charge (Neutral) and with Tc-99m autologous red cells. Liposomes (135 nm diameter) encapsulating glutathione were labeled with Tc-99m using the lipophilic chelator, HMPAO as previously described. Autologous red cells were labeled using an Ultratag kit. Labeling efficiencies averaged 66%, 52%, and 97% for the PEG liposomes. Neutral liposomes, and red cells, respectively. Rabbits (3-3.5 Kg) were injected IV via ear vein with 2.0 mls of PEG liposomes (2 mCi, 17 mg phospholipid/Kg body weight, n=5). Neutral liposomesmore » (1.3 mCi, 17 mg phospholipid/Kg body weight, n=4), or red cells (2.6 mCi, n=2). Gamma camera images were acquired at 5,22, and 45 minutes, and 2,20,and 44 hours post-injection. Blood samples were obtained at each time point to determine clearance kinetics. Circulation half lives of both Tc-99m liposome formulations were longer than Tc-99m red cells (8 hrs), with the half life of PEG liposomes (35 hrs) 1.6 times longer than Neutral liposomes (22 hrs). In vivo stability of the Tc-99m label was excellent for the liposomes with only 3.5-4% bladder activity at 45 minutes compared to 12% bladder activity for the red cells. Excellent blood pool images were obtained for the PEG liposomes in the rabbit. Heart/liver ratios calculated from region of interest analysis of 45 minutes images were 1.9, 1.5, and 1.7 for PEG liposomes, Neutral liposomes and red cells. This study demonstrates the feasibility of using Tc-99m PEG liposomes to perform gated cardiac blood pool and rapid gastrointestinal bleeding studies.« less

Treatment of Refractory Filamentary Keratitis With Autologous Serum Tears.

PubMed

Read, Sarah P; Rodriguez, Marianeli; Dubovy, Sander; Karp, Carol L; Galor, Anat

2017-09-01

To report a case of filamentary keratitis (FK) successfully treated with autologous serum tears and to review the pathogenesis and management of FK. Case report including high-resolution anterior segment optical coherence tomography and filament histopathology. A 61-year-old Hispanic man presented with pain and photophobia of the right eye. He was found to have a corneal epithelial defect and a small peripheral infiltrate 4 months after Laser Assisted in situ Keratomileusis. After resolution of the epithelial defect, he developed FK. Over a 4-month period, conservative management with aggressive lubrication, lid hygiene, topical corticosteroids, topical cyclosporine, bandage contact lenses, and oral doxycycline failed to resolve the corneal filaments. Notably, treatment with 20% autologous serum tears, four times daily, led to a sustained resolution of the FK within 1 week. This case demonstrates the complexity of FK management and introduces autologous serum tears as a viable management option when conservative approaches to this condition fail.

Lumbar herniation following extended autologous latissimus dorsi breast reconstruction.

PubMed

Fraser, Sheila Margaret; Fatayer, Hiba; Achuthan, Rajgopal

2013-05-30

Reconstructive breast surgery is now recognized to be an important part of the treatment for breast cancer. Surgical reconstruction options consist of implants, autologous tissue transfer or a combination of the two. The latissimus dorsi flap is a pedicled musculocutaneous flap and is an established method of autologous breast reconstruction.Lumbar hernias are an unusual type of hernia, the majority occurring after surgery or trauma in this area. The reported incidence of a lumbar hernia subsequent to a latissimus dorsi reconstruction is very low. We present the unusual case of lumbar herniation after an extended autologous latissimus dorsi flap for breast reconstruction following a mastectomy. The lumbar hernia was confirmed on CT scanning and the patient underwent an open mesh repair of the hernia through the previous latissimus dorsi scar. Lumbar hernias are a rare complication that can occur following latissimus dorsi breast reconstruction. It should be considered in all patients presenting with persistent pain or swelling in the lumbar region.

Phenotypic differences in leucocyte populations among healthy preterm and full-term newborns.

PubMed

Quinello, C; Silveira-Lessa, A L; Ceccon, M E J R; Cianciarullo, M A; Carneiro-Sampaio, M; Palmeira, P

2014-07-01

The immune system of neonates has been considered functionally immature, and due to their high susceptibility to infections, the aim of this study was to analyse the phenotypic differences in leucocyte populations in healthy preterm and full-term newborns. We evaluated the absolute numbers and frequencies of dendritic cells (DCs) and DC subsets, monocytes and T and B lymphocytes and subsets in the cord blood of healthy moderate and very preterm (Group 1), late preterm (Group 2) and full-term (Group 3) newborns and in healthy adults, as controls, by flow cytometry. The analyses revealed statistically higher absolute cell numbers in neonates compared with adults due to the characteristic leucocytosis of neonates. We observed a lower frequency of CD80(+) myeloid and plasmacytoid DCs in Group 1 and reduced expression of TLR-4 on myeloid DCs in all neonates compared with adults. TLR-2(+) monocytes were reduced in Group 1 compared with Groups 2 and 3, and TLR-4(+) monocytes were reduced in Groups 1 and 2 compared with Group 3. The frequencies and numbers of naïve CD4(+) T and CD19(+) B cells were higher in the three groups of neonates compared with adults, while CD4(+) effector and effector memory T cells and CD19(+) memory B cells were elevated in adults compared with neonates, as expected. Our study provides reference values for leucocytes in cord blood from term and preterm newborns, which may facilitate the identification of immunological deficiencies in protection against extracellular pathogens. © 2014 John Wiley & Sons Ltd.

Autologous Platelet-Rich Plasma Preparations

PubMed Central

Schippinger, Gert; Prüller, Florian; Divjak, Manuela; Mahla, Elisabeth; Fankhauser, Florian; Rackemann, Steve; Raggam, Reinhard Bernd

2015-01-01

Background Autologous platelet-rich plasma (PRP) has been widely used for the treatment of sports injuries. It has been associated with improved healing and regeneration of soft tissues in elite athletes. Athletes are commonly receiving nonsteroidal anti-inflammatory drugs (NSAIDs). As yet, the effect of these drugs on platelet function in PRP formulations has not been taken into consideration. Hypothesis The function of platelets in PRP produced under the influence of NSAIDs is inhibited and may lessen a possible healing effect on the site of injury. Study Design Controlled laboratory study. Methods PRP was collected from patients receiving NSAIDs after elective orthopaedic surgery, and platelet function was evaluated using light transmission aggregometry (LTA). Results were compared with those obtained from healthy volunteers without a history of NSAID intake during the previous 2 weeks. Two different systems for blood collection and PRP production (Arthrex ACP double-syringe system and standard 4.5-mL sodium citrate blood collection tubes) were used and compared regarding the quality of PRP that was produced. Results For both groups, the baseline platelet counts of whole blood and the platelet counts of PRP formulations were found to be in the normal range. Both collection systems for PRP produced comparable results without significant differences between the groups. Platelet function testing with LTA revealed significantly impaired platelet aggregation in both PRP preparations, obtained from patients taking NSAIDs, irrespective of the type of NSAID (P < .001). All subjects from the control group showed normal platelet aggregation patterns when tested with LTA. Conclusion Autologous PRP produced from subjects after NSAID medication shows significantly impaired platelet function and may result in lower quality regarding the content of bioactive compounds. Clinical Relevance If required, the administration of NSAIDs should be performed after blood collection for

In vitro effects of prostaglandin E2 on leucocytes from sticklebacks (Gasterosteus aculeatus) infected and not infected with the cestode Schistocephalus solidus.

PubMed

Kutyrev, Ivan A; Franke, Frederik; Büscher, Janine; Kurtz, Joachim; Scharsack, Jörn P

2014-12-01

Many helminth parasites have evolved strategies to evade the immune response of their hosts, which includes immunomodulation. Prostaglandin E2 (PGE2) is one of the best-described immunomodulators in mammalian helminth parasite infections. We hypothesized that also in teleost fish anti-helminthic immune responses are regulated via PGE2. We used a model system consisting of the tapeworm Schistocephalus solidus and its host, the three-spined stickleback (Gasterosteus aculeatus), to investigate in vitro effects of PGE2 on head kidney leucocytes (HKL) derived from sticklebacks that were experimentally infected with S. solidus. PGE2 was tested alone or in combination with either S. solidus antigens or bacterial lipopolysaccharides (LPS). After in vitro culture, cell viability and changes in leucocyte subpopulations (granulocytes to lymphocytes ratios) were monitored by flow cytometry and HKL were tested for their capacity to produce reactive oxygen species (ROS) with a chemiluminescence assay. In short term (2 h) HKL cultures PGE2 did not change the total numbers of live HKL, but the production of ROS decreased significantly with high (0.1 μmol L(-1)) PGE2 concentrations. In long-term (96 h) cultures high PGE2 concentrations induced a sharp decrease of leucocytes viability, while low (0.1 pmol L(-1)) and intermediate (0.1 nmol L(-1)) concentrations of PGE2 caused elevated leucocyte viability compared to controls. This coincided with reduced ROS production in cultures with high PGE2 and elevated ROS production in cultures with low PGE2. Granulocyte to lymphocyte ratios increased with high PGE2 concentrations alone and in combination with S. solidus antigens and LPS, most prominently with HKL from S. solidus infected sticklebacks. The present study supports the hypothesis that PGE2 might be an immunomodulator in tapeworm-fish parasite-host interactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Autologous Platelet-Poor Plasma Gel for Injection Laryngoplasty

PubMed Central

Woo, Seung Hoon; Kim, Jin Pyeong; Park, Jung Je; Chung, Phil-Sang

2013-01-01

Purpose To overcome the potential disadvantages of the use of foreign materials and autologous fat or collagen, we introduce here an autologous plasma gel for injection laryngoplasty. The purpose of this study was to present a new injection material, a plasma gel, and to discuss its clinical effectiveness. Materials and Methods From 2 mL of blood, the platelet poor serum layer was collected and heated at 100℃ for 12 min to form a plasma gel. The plasma gel was then injected into a targeted site; the safety and efficacy thereof were evaluated in 30 rats. We also conducted a phase I/II clinical study of plasma gel injection laryngoplasty in 11 unilateral vocal fold paralysis patients. Results The plasma gel was semi-solid and an easily injectable material. Of note, plasma gel maintains the same consistency for up to 1 year in a sealed bottle. However, exposure to room air causes the plasma gel to disappear within 1 month. In our animal study, the autologous plasma gel remained in situ for 6 months in animals with minimal inflammation. Clinical study showed that vocal cord palsy was well compensated for with the plasma gel in all patients at two months after injection with no significant complications. Jitter, shimmer, maximum, maximum phonation time (MPT) and mean voice handicap index (VHI) also improved significantly after plasma gel injection. However, because the injected plasma gel was gradually absorbed, 6 patients needed another injection, while the gel remained in place in 2 patients. Conclusion Injection laryngoplasty with autologous plasma gel may be a useful and safe treatment option for temporary vocal cord palsy. PMID:24142660

EXPERIMENTAL STUDIES ON INFLAMMATION : I. THE INFLUENCE OF CHEMICALS UPON THE CHEMOTAXIS OF LEUCOCYTES IN VITRO.

PubMed

Wolf, E P

1921-09-30

1. Wright's method for the study of chemotaxis of leucocytes in vitro, slightly modified, has been found to be most satisfactory in the estimation of the degree of chemotaxis of various substances, because it is possible to make an exact quantitative determination of the leucocytes that have migrated from the blood clot and adhere to the surfaces containing the tested substance. 2. The calcium ion is the only inorganic ion per se which is found to be positively chemotactic under the conditions of these experiments. It is markedly chemotactic in all concentrations and in all combinations, except the citrate. Here the negative chemotaxis of the citrate ion neutralizes the positive chemotaxis of the calcium ion, and neutrality of chemotactic effect results. 3. The sodium and magnesium ions themselves are neutral. Magnesium and sodium salts are dependent upon the negative ion with which the magnesium or sodium is combined for such positive or negative chemotaxis as is exhibited. All the phosphates of sodium, whether tri-, di-, or monobasic salts, are markedly positively chemotactic, and when combined with other reagents which are themselves neutral or negatively chemotactic, produce marked positive chemotaxis. The blood of a person who has taken phosphates either by mouth or intravenously shows a great increase in chemotaxis with sodium phosphate, with calcium chloride, and even with sodium chloride which is ordinarily neutral. 4. All potassium salts are negatively chemotactic. 5. Many substances act synergistically as regards chemotaxis; e.g., when strontium and magnesium salts are mixed there is a marked increase in chemotaxis. Sodium phosphate acts synergistically with calcium chloride. 6. Mercury salts fix the leucocytes in this method so that their influence on chemotaxis cannot be determined. 7. Morphine and morphine salts are positively chemotactic; this is contrary to the results obtained by others with different methods. 8. Substances which produce a very

Intestinal bacteria modify lymphoma incidence and latency by affecting systemic inflammatory state, oxidative stress, and leucocyte genotoxicity

PubMed Central

Yamamoto, Mitsuko L.; Maier, Irene; Dang, Angeline Tilly; Berry, David; Liu, Jared; Ruegger, Paul M.; Yang, Jiue-in; Soto, Phillip A.; Presley, Laura L.; Reliene, Ramune; Westbrook, Aya M.; Wei, Bo; Loy, Alexander; Chang, Christopher; Braun, Jonathan; Borneman, James; Schiestl, Robert H.

2013-01-01

Ataxia-telangiectasia (A-T) is a genetic disorder associated with high incidence of B cell lymphoma. Using an A-T mouse model, we compared lymphoma incidence in several isogenic mouse colonies harboring different bacterial communities, finding that intestinal microbiota are a major contributor to disease penetrance and latency, lifespan, molecular oxidative stress and systemic leucocyte genotoxicity. High throughput sequence analysis of rRNA genes identified mucosa-associated bacterial phylotypes that were colony-specific. Lactobacillus johnsonii, which was deficient in the more cancer-prone mouse colony, was causally tested for its capacity to confer reduced genotoxicity when restored by short-term oral transfer. This intervention decreased systemic genotoxicity, a response associated with reduced basal leucocytes and the cytokine-mediated inflammatory state, and mechanistically linked to the host cell biology of systemic genotoxicity. Our results suggest that intestinal microbiota are a potentially modifiable trait for translational intervention in individuals at risk for B cell lymphoma, or for other diseases that are driven by genotoxicity or the molecular response to oxidative stress. PMID:23860718

Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.

PubMed

Bradley, Todd; Fera, Daniela; Bhiman, Jinal; Eslamizar, Leila; Lu, Xiaozhi; Anasti, Kara; Zhang, Ruijung; Sutherland, Laura L; Scearce, Richard M; Bowman, Cindy M; Stolarchuk, Christina; Lloyd, Krissey E; Parks, Robert; Eaton, Amanda; Foulger, Andrew; Nie, Xiaoyan; Karim, Salim S Abdool; Barnett, Susan; Kelsoe, Garnett; Kepler, Thomas B; Alam, S Munir; Montefiori, David C; Moody, M Anthony; Liao, Hua-Xin; Morris, Lynn; Santra, Sampa; Harrison, Stephen C; Haynes, Barton F

2016-01-05

Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Leucocyte classification for leukaemia detection using image processing techniques.

PubMed

Putzu, Lorenzo; Caocci, Giovanni; Di Ruberto, Cecilia

2014-11-01

The counting and classification of blood cells allow for the evaluation and diagnosis of a vast number of diseases. The analysis of white blood cells (WBCs) allows for the detection of acute lymphoblastic leukaemia (ALL), a blood cancer that can be fatal if left untreated. Currently, the morphological analysis of blood cells is performed manually by skilled operators. However, this method has numerous drawbacks, such as slow analysis, non-standard accuracy, and dependences on the operator's skill. Few examples of automated systems that can analyse and classify blood cells have been reported in the literature, and most of these systems are only partially developed. This paper presents a complete and fully automated method for WBC identification and classification using microscopic images. In contrast to other approaches that identify the nuclei first, which are more prominent than other components, the proposed approach isolates the whole leucocyte and then separates the nucleus and cytoplasm. This approach is necessary to analyse each cell component in detail. From each cell component, different features, such as shape, colour and texture, are extracted using a new approach for background pixel removal. This feature set was used to train different classification models in order to determine which one is most suitable for the detection of leukaemia. Using our method, 245 of 267 total leucocytes were properly identified (92% accuracy) from 33 images taken with the same camera and under the same lighting conditions. Performing this evaluation using different classification models allowed us to establish that the support vector machine with a Gaussian radial basis kernel is the most suitable model for the identification of ALL, with an accuracy of 93% and a sensitivity of 98%. Furthermore, we evaluated the goodness of our new feature set, which displayed better performance with each evaluated classification model. The proposed method permits the analysis of blood cells

Regular exercise during haemodialysis promotes an anti-inflammatory leucocyte profile

PubMed Central

Dungey, Maurice; Young, Hannah M L; Churchward, Darren R; Burton, James O; Smith, Alice C

2017-01-01

Abstract Background Cardiovascular disease is the most common cause of mortality in haemodialysis (HD) patients and is highly predicted by markers of chronic inflammation. Regular exercise may have beneficial anti-inflammatory effects, but this is unclear in HD patients. This study assessed the effect of regular intradialytic exercise on soluble inflammatory factors and inflammatory leucocyte phenotypes. Methods Twenty-two HD patients from a centre where intradialytic cycling was offered thrice weekly and 16 HD patients receiving usual care volunteered. Exercising patients aimed to cycle for 30 min at rating of perceived exertion of ‘somewhat hard’. Baseline characteristics were compared with 16 healthy age-matched individuals. Physical function, soluble inflammatory markers and leucocyte phenotypes were assessed again after 6 months of regular exercise. Results Patients were less active than their healthy counterparts and had significant elevations in measures of inflammation [interleukin-6 (IL-6), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), intermediate and non-classical monocytes; all P < 0.001]. Six months of regular intradialytic exercise improved physical function (sit-to-stand 60). After 6 months, the proportion of intermediate monocytes in the exercising patients reduced compared with non-exercisers (7.58 ± 1.68% to 6.38 ± 1.81% versus 6.86 ± 1.45% to 7.88 ± 1.66%; P < 0.01). Numbers (but not proportion) of regulatory T cells decreased in the non-exercising patients only (P < 0.05). Training had no significant effect on circulating IL-6, CRP or TNF-α concentrations. Conclusions These findings suggest that regular intradialytic exercise is associated with an anti-inflammatory effect at a circulating cellular level but not in circulating cytokines. This may be protective against the increased risk of cardiovascular disease and mortality that is associated with chronic inflammation and elevated numbers

Prospective randomized comparison of scar appearances between cograft of acellular dermal matrix with autologous split-thickness skin and autologous split-thickness skin graft alone for full-thickness skin defects of the extremities.

PubMed

Yi, Ju Won; Kim, Jae Kwang

2015-03-01

The purpose of this study was to evaluate the clinical outcomes of cografting of acellular dermal matrix with autologous split-thickness skin and autologous split-thickness skin graft alone for full-thickness skin defects on the extremities. In this prospective randomized study, 19 consecutive patients with full-thickness skin defects on the extremities following trauma underwent grafting using either cograft of acellular dermal matrix with autologous split-thickness skin graft (nine patients, group A) or autologous split-thickness skin graft alone (10 patients, group B) from June of 2011 to December of 2012. The postoperative evaluations included observation of complications (including graft necrosis, graft detachment, or seroma formation) and Vancouver Scar Scale score. No statistically significant difference was found regarding complications, including graft necrosis, graft detachment, or seroma formation. At week 8, significantly lower Vancouver Scar Scale scores for vascularity, pliability, height, and total score were found in group A compared with group B. At week 12, lower scores for pliability and height and total scores were identified in group A compared with group B. For cases with traumatic full-thickness skin defects on the extremities, a statistically significant better result was achieved with cograft of acellular dermal matrix with autologous split-thickness skin graft than with autologous split-thickness skin graft alone in terms of Vancouver Scar Scale score. Therapeutic, II.

Use of containers with sterilizing filter in autologous serum eyedrops.

PubMed

López-García, José S; García-Lozano, Isabel

2012-11-01

To assess the effect of the use of containers with an adapted sterilizing filter on the contamination of autologous serum eyedrops. Prospective, consecutive, comparative, and randomized study. Thirty patients with Sjögren syndrome. One hundred seventy-six autologous serum containers used in home therapy were studied; 48 of them included an adapted filter (Hyabak; Thea, Clermont-Ferrand, France), and the other 128 were conventional containers. Containers equipped with a filter were tested at 7, 14, 21, and 28 days of use, whereas conventional containers were studied after 7 days of use. In addition, testing for contamination was carried out in 14 conventional containers used during in-patient therapy every week for 4 weeks. In all cases, the preparation of the autologous serum was similar. Blood agar and chocolate agar were used as regular culture media for the microbiologic studies, whereas Sabouraud agar with chloramphenicol was the medium for fungal studies. Microbiologic contamination of containers with autologous serum eyedrops. Only one of the containers with an adapted sterilizing filter (2.1%) became contaminated with Staphylococcus epidermidis after 1 month of treatment, whereas the contamination rate among conventional containers reached 28.9% after 7 days of treatment. The most frequent germs found in the samples were coagulase-negative Staphylococcus (48.6%). With regard the containers used in the in-patient setting, 2 (14.3%) became contaminated after 2 weeks, 5 (35.7%) became contaminated after 3 weeks, and 5 (50%) became contaminated after 4 weeks, leaving 7 (50%) that did not become contaminated after 1 month of treatment. Using containers with an adapted filter significantly reduces the contamination rates in autologous serum eyedrops, thus extending the use of such container by the patients for up to 4 weeks with virtually no contamination risks. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A clinical study on the feasibility of autologous cord blood transfusion for anemia of prematurity.

PubMed

Khodabux, Chantal M; von Lindern, Jeannette S; van Hilten, Joost A; Scherjon, Sicco; Walther, Frans J; Brand, Anneke

2008-08-01

The objective was to investigate the use of autologous red blood cells (RBCs) derived from umbilical cord blood (UCB), as an alternative for allogeneic transfusions in premature infants admitted to a tertiary neonatal center. UCB collection was performed at deliveries of less than 32 weeks of gestation and processed into autologous RBC products. Premature infants requiring a RBC transfusion were randomly assigned to an autologous or allogeneic product. The primary endpoint was an at least 50 percent reduction in allogeneic transfusion needs. Fifty-seven percent of the collections harvested enough volume (> or =15 mL) for processing. After being processed, autologous products (> or =10 mL/kg) were available for 36 percent of the total study population and for 27 percent of the transfused infants and could cover 58 percent (range, 25%-100%) of the transfusion needs within the 21-day product shelf life. Availability of autologous products depended most on the gestational age. Infants born between 24 and 28 weeks had the lowest availability (17%). All products, however, would be useful in view of their high (87%) transfusion needs. Availability was highest (48%) for the infants born between 28 and 30 weeks. For 42 percent of the infants with transfusion needs in this group, autologous products were available. For the infants born between 30 and 32 weeks, autologous products were available for 36 percent of the infants. Transfusion needs in this group were, however, much lower (19%) compared to the other gestational groups. Autologous RBCs derived from UCB could not replace 50 percent of allogeneic transfusions due to the low UCB volumes collected and subsequent low product availability.

Safety and effectiveness of predeposit autologous transfusions in preteen and adolescent children.

PubMed

Silvergleid, A J

1987-06-26

Although there is documentation in the literature of the safety and effectiveness of predeposit autologous transfusions among adult patients contemplating surgery, there are no comparable data for preteen and teenage children. We report our experience with 180 children between the ages of 8 and 18 years participating in a community blood center-based predeposit autologous transfusion program. Children as young as 8 years old and weighing as little as 27 kg predonated a prescribed amount of blood prior to elective orthopedic (169) or plastic (11) surgery. Only four children experienced a donor reaction; none of them was severe. No child was unable to donate the prescribed number of units. Eighty-eight percent of the children were able to supply their complete blood requirements, thus avoiding exposure to homologous blood. Our experience documents both the safety and effectiveness of predeposit autologous transfusions in preteen and adolescent children and should encourage existing predeposit autologous transfusion programs to extend participation to thousands of children for whom the opportunity to use their own blood is currently denied.

The Composite of Bone Marrow Concentrate and PRP as an Alternative to Autologous Bone Grafting

PubMed Central

Hakimi, Mohssen; Grassmann, Jan-Peter; Betsch, Marcel; Schneppendahl, Johannes; Gehrmann, Sebastian; Hakimi, Ahmad-Reza; Kröpil, Patric; Sager, Martin; Herten, Monika; Wild, Michael; Windolf, Joachim; Jungbluth, Pascal

2014-01-01

One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC). The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP) in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group). In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG), whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold) compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting. PMID:24950251

Behavior of autologous indium-114m-labeled lymphocytes in patients with lymphoid cell malignancy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, D.; Cowan, R.A.; Sharma, H.L.

1988-04-01

It has been shown that radioactive material can be localized to lymphocyte traffic areas using radiolabeled autologous lymphocytes and that /sup 114m/In deposited in such a way in rats produces a lymphopoenia by establishing a selective internal irradiation of circulating lymphocytes. The study reported here was undertaken to investigate the feasibility of using this technique in patients with lymphoid cell malignancy. Up to 22.7 MBq was administered to seven patients with active non-Hodgkin's lymphoma involving the spleen and the behavior of the radioactive material was followed over subsequent months. Estimates of the activity in peripheral blood, bone marrow, excreta samples,more » and of the variation in the whole-body distribution were obtained. The administered radioactive material cleared rapidly from the blood, 85% being removed within the first 30 min. There was an almost immediate uptake of most of this by the spleen and liver with less than 5% of administered activity accumulating in the bone marrow. After 48 hr, the whole-body distribution changed only slowly and there was a regular decrease of the activity in the spleen. Excretion of radioactive material occurred via both the urine and feces and amounted to less than 1% of administered activity per day. This pharmacokinetic data was used to calculate radiation absorbed doses to various organs for a standard man. It is concluded that this represents a feasible technique for the targeting of radioactive material for the treatment of lymphoid malignancy.« less

In vitro effects of virgin microplastics on fish head-kidney leucocyte activities.

PubMed

Espinosa, Cristóbal; García Beltrán, José María; Esteban, María Angeles; Cuesta, Alberto

2018-04-01

Microplastics are well-documented pollutants in the marine environment that result from production or fragmentation of larger plastic items. The knowledge about the direct effects of microplastics on immunity, including fish, is still very limited. We investigated the in vitro effects of microplastics [polyvinylchloride (PVC) and polyethylene (PE)] on gilthead seabream (Sparus aurata) and European sea bass (Dicentrarchus labrax) head-kidney leucocytes (HKLs). After 1 and 24 h of exposure of HKLs with 0 (control), 1, 10 and 100 mg mL -1 MPs in a rotatory system, cell viability, innate immune parameters (phagocytic, respiratory burst and peroxidase activities) and the expression of genes related to inflammation (il1b), oxidative stress (nrf2, prdx3), metabolism of xenobiotics (cyp1a1, mta) and cell apoptosis (casp3) were studied. Microplastics failed to affect the cell viability of HKLs. In addition, they provoke very few significant effects on the main cellular innate immune activities, as decrease on phagocytosis or increase in the respiratory burst of HKLs with the highest dose of microplastics tested. Furthermore, microplastics failed to affect the expression of the selected genes on sea bass or seabream, except the nrf2 which was up-regulated in seabream HKLs incubated with the highest doses. Present results seem to suggest that continue exposure of fish to PVC or PE microplastics could impair fish immune parameters probably due to the oxidative stress produced in the fish leucocytes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Management of vocal fold scar with autologous fat implantation: perceptual results.

PubMed

Neuenschwander, M C; Sataloff, R T; Abaza, M M; Hawkshaw, M J; Reiter, D; Spiegel, J R

2001-06-01

Vocal fold scar disrupts the mucosal wave and interferes with glottic closure. Treatment involves a multidisciplinary approach that includes voice therapy, medical management, and sometimes surgery. We reviewed the records of the first eight patients who underwent autologous fat implantation for vocal fold scar. Information on the etiology of scar, physical findings, and prior interventions were collected. Videotapes of videostroboscopic findings and perceptual voice ratings [Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS)] were randomized and analyzed independently by four blinded observers. Etiology of scar included mass excision (7), vocal fold stripping (3), congenital sulcus (2), and hemorrhage (1). Prior surgical procedures performed included thyroplasty (1), autologous fat injection (9), excision of scar (2), and lysis of adhesions (2). Strobovideolaryngoscopy: Statistically significant improvement was found in glottic closure, mucosal wave, and stiffness (P = 0.05). Perceptual ratings (GRBAS): Statistically significant improvement was found in all five parameters, including overall Grade, Roughness, Breathiness, Asthenia, and Strain (P = 0.05). Patients appear to have improved vocal fold function and quality of voice after autologous fat implantation in the vocal fold. Autologous fat implantation is an important adjunctive procedure in the management of vocal fold scar, and a useful addition to the armamentarium of the experienced phonomicrosurgeon.

Mastectomy Skin Necrosis After Breast Reconstruction: A Comparative Analysis Between Autologous Reconstruction and Implant-Based Reconstruction.

PubMed

Sue, Gloria R; Lee, Gordon K

2018-05-01

Mastectomy skin necrosis is a significant problem after breast reconstruction. We sought to perform a comparative analysis on this complication between patients undergoing autologous breast reconstruction and patients undergoing 2-stage expander implant breast reconstruction. A retrospective review was performed on consecutive patients undergoing autologous breast reconstruction or 2-stage expander implant breast reconstruction by the senior author from 2006 through 2015. Patient demographic factors including age, body mass index, history of diabetes, history of smoking, and history of radiation to the breast were collected. Our primary outcome measure was mastectomy skin necrosis. Fisher exact test was used for statistical analysis between the 2 patient cohorts. The treatment patterns of mastectomy skin necrosis were then analyzed. We identified 204 patients who underwent autologous breast reconstruction and 293 patients who underwent 2-stage expander implant breast reconstruction. Patients undergoing autologous breast reconstruction were older, heavier, more likely to have diabetes, and more likely to have had prior radiation to the breast compared with patients undergoing implant-based reconstruction. The incidence of mastectomy skin necrosis was 30.4% of patients in the autologous group compared with only 10.6% of patients in the tissue expander group (P < 0.001). The treatment of this complication differed between these 2 patient groups. In general, those with autologous reconstructions were treated with more conservative means. Although 37.1% of patients were treated successfully with local wound care in the autologous group, only 3.2% were treated with local wound care in the tissue expander group (P < 0.001). Less than half (29.0%) of patients in the autologous group were treated with an operative intervention for this complication compared with 41.9% in the implant-based group (P = 0.25). Mastectomy skin necrosis is significantly more likely to occur after

[Breast reconstruction: autologous tissue versus implant].

PubMed

Plogmeier, K; Handstein, S; Schneider, W

1998-01-01

Modified radical mastectomy remains the standard for treatment of breast cancer. Women faced with the diagnosis of breast cancer often find it difficult to cope with the arousing emotions. Fear of death or cancer recurrence and a perceived loss of femininity often coexists with the desire for a return to normality and wholeness. For women seeking breast reconstruction various techniques have been developed. Two different ways for breast reconstruction have become a standard. One way is the reconstruction by tissue expansion or transposing locally available tissue with the use of implants. The other way is the reconstruction of the breast without using any implants with the Latissimus dorsi flap or the TRAM flap. We performed 291 breast reconstructions. In 125 women available tissue and an implant was used. The Latissimus dorsi flap was used in 57 cases and 109 TRAM flaps either pedicled or as a microvascular flap were performed. Using expanders we found a perforation of the device in 2 cases. After using implants there were capsular contracture in 2 cases and in 1 case we had an infection. Using autologous tissue we had 2 partial flap necrosis, 4 hematomas, and 4 prolonged healings. There was no complete flap necrosis. Breast reconstruction using autologous tissue i.e. the TRAM flap is supposed to be a standard technique. Microsurgical transplantation of the TRAM flap shows almost no morbidity of the donor site area. Autologous tissue follows the changes of the body like weight gain or reduction to a certain extend and shows neither capsular contracture nor other implant associated side effects. Women get the impression that the TRAM flap is like soft tissue to the touch and not like a foreign body. The aesthetic results were in all cases superior sometimes needing minor secondary correction and mostly shaping of the nippel-areola complex. All patients were pleased with the result.

Tissue-Engineered Autologous Grafts for Facial Bone Reconstruction

PubMed Central

Bhumiratana, Sarindr; Bernhard, Jonathan C.; Alfi, David M.; Yeager, Keith; Eton, Ryan E.; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M.; Lopez, Mandi J.; Eisig, Sidney B.; Vunjak-Novakovic, Gordana

2016-01-01

Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, without bone morphogenic proteins, using native bovine bone matrix and a perfusion bioreactor for the growth and transport of living grafts. The ramus-condyle unit (RCU), the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatan minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material, and crafted it into an anatomically correct shape using image-guided micromilling, to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either non-seeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. PMID:27306665

Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing

PubMed Central

Neves, Paulo César Fagundes; de Campos Vieira Abib, Simone; Neves, Rogério Fagundes; Pircchio, Oronzo; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Simões, Ricardo Santos; Moreira, Marcia Bento; de Souza Laurino, Cristiano Frota

2013-01-01

OBJECTIVES: The purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures. METHODS: A total of 128 male New Zealand albino rabbits, between 6–8 months old, were subjected to a total osteotomy of the proximal portion of the right fibula. After surgery, the animals were divided into four groups (n = 32 each): control group, in which animals were subjected to osteotomy; autologous platelet concentrate group, in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site; hyperbaric oxygen group, in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions; and autologous platelet concentrate and hyperbaric oxygen group, in which animals were subjected to osteotomy, autologous platelet concentrate applied at the fracture site, and 9 consecutive daily hyperbaric oxygen therapy sessions. Each group was divided into 4 subgroups according to a pre-determined euthanasia time points: 2, 4, 6, and 8 weeks postoperative. After euthanasia at a specific time point, the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red. RESULTS: Autologous platelet concentrates and hyperbaric oxygen therapy, applied together or separately, increased the rate of bone healing compared with the control group. CONCLUSION: Hyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model. PMID:24141841

[Post-anesthetic autologous blood donation used in knee and hip arthroplasty].

PubMed

Wei, Wei; Kou, Bolong; Ju, Rongseng

2006-06-01

To explore the clinical application of the postanesthetic autologous donation and the postoperative transfusion during the knee and hip replacement surgeries. Thirty-three patients (17 males, 16 females) admitted for the elective joint replacement surgeries from September 2004 to January 2005 were included in this study. Of the 33 patients, 5 were diagnosed with rheumatoid arthritis, 23 with femoral head necrosis, and 5 with knee osteoarthritis. Immediately after anesthesia, 400 ml of the blood was drawn and transfused after the surgery. The blood pressure was monitored during the blood drawing, postoperative blood parameters were recorded, surgical site drainage and signs of infections were observed, and the other clinical data were collected. Of the 33 patients, 27 only received autologous transfusion, including 21 patients who underwent the unilateral hip replacement and 6 patients who underwent the unilateral knee replacement. All these 6 patients with the unilateral knee replacement received the blood drained from the surgical sites in addition to the blood obtained from the post-anesthetic autologous donation. Another 6 cases with the bilateral hip and knee replacement received the blood drained from the surgical sites, the blood obtained from the post-anesthetic autologous donation and 400 ml of the allogeneic blood transfusion. The blood received postoperatively averaged 650 ml (range, 200-1 150 ml), haemoglobin (Hb) was averaged 88 g/L (68-102 g/L), and Hct was averaged 24.6% (20.5%-31.5%). Hb and Hct were lower after operation than before operation (P < 0.01). Postoperative blood transfusion following the postanesthetic and preoperative autologous donation can be successfully applied to most of the patients undergoing the knee or hip replacement so as to reduce complications of the allogeneic blood transfusion.

Normal platelet function in platelet concentrates requires non-platelet cells: a comparative in vitro evaluation of leucocyte-rich (type 1a) and leucocyte-poor (type 3b) platelet concentrates

PubMed Central

Parrish, William R; Roides, Breana; Hwang, Julia; Mafilios, Michael; Story, Brooks; Bhattacharyya, Samir

2016-01-01

Background Therapeutic success of platelet-rich plasma (PRP) may vary based on the composition and preparation method. The objective of this study was to evaluate the cellular components of platelet concentrates produced by a leucocyte-rich (LR-PRP) and a leucocyte-poor PRP systems (LP-PRP). Methods Parameters evaluated included platelet recovery, platelet concentration, red blood cell (RBC) and white blood cell (WBC) composition, platelet growth factor release and stimulation of human tendon cell proliferation in vitro. Results Platelet recoveries were 52% for LP-PRP and 89% for LR-PRP. LR-PRP demonstrated greater reproducibility with a 4.2% coefficient of variation (CV) compared with 19.4% for LP-PRP (p<0.001). LR-PRP demonstrated a greater increase in platelet concentration (7.9-fold) than LP-PRP (2.2-fold; p<0.001). LP-PRP showed 5.0-fold reductions in WBCs, while LR-PRP showed a 4.0-fold increase (p<0.001). LP-PRP reduced RBCs to a haematocrit of 0.25, while LR-PRP reduced haematocrit to 11.8. LP-PRP did not coagulate robustly on reactivation with CaCl2, and released significantly lower levels of epidermal growth factor (EGF) and transforming growth factor β1 (TGF-β1) than whole blood (p<0.03). LP-PRP also did not stimulate tendon cell proliferation greater than whole blood. In contrast, LR-PRP showed increases in each growth factor on activation with CaCl2 (p<0.01) and stimulated greater proliferation (p<0.05) compared with whole blood. Forced activation of LP-PRP with exogenous thrombin rescued the coagulation deficiency and induced greater growth factor release than comparable whole blood (p<0.03). Conclusions These data suggest that non-platelet cellular components in platelet concentrates are important for proper platelet function, including thrombin generation, growth factor release and clot retraction. PMID:27900155

Normal platelet function in platelet concentrates requires non-platelet cells: a comparative in vitro evaluation of leucocyte-rich (type 1a) and leucocyte-poor (type 3b) platelet concentrates.

PubMed

Parrish, William R; Roides, Breana; Hwang, Julia; Mafilios, Michael; Story, Brooks; Bhattacharyya, Samir

2016-01-01

Therapeutic success of platelet-rich plasma (PRP) may vary based on the composition and preparation method. The objective of this study was to evaluate the cellular components of platelet concentrates produced by a leucocyte-rich (LR-PRP) and a leucocyte-poor PRP systems (LP-PRP). Parameters evaluated included platelet recovery, platelet concentration, red blood cell (RBC) and white blood cell (WBC) composition, platelet growth factor release and stimulation of human tendon cell proliferation in vitro. Platelet recoveries were 52% for LP-PRP and 89% for LR-PRP. LR-PRP demonstrated greater reproducibility with a 4.2% coefficient of variation (CV) compared with 19.4% for LP-PRP (p<0.001). LR-PRP demonstrated a greater increase in platelet concentration (7.9-fold) than LP-PRP (2.2-fold; p<0.001). LP-PRP showed 5.0-fold reductions in WBCs, while LR-PRP showed a 4.0-fold increase (p<0.001). LP-PRP reduced RBCs to a haematocrit of 0.25, while LR-PRP reduced haematocrit to 11.8. LP-PRP did not coagulate robustly on reactivation with CaCl 2 , and released significantly lower levels of epidermal growth factor (EGF) and transforming growth factor β1 (TGF-β1) than whole blood (p<0.03). LP-PRP also did not stimulate tendon cell proliferation greater than whole blood. In contrast, LR-PRP showed increases in each growth factor on activation with CaCl 2 (p<0.01) and stimulated greater proliferation (p<0.05) compared with whole blood. Forced activation of LP-PRP with exogenous thrombin rescued the coagulation deficiency and induced greater growth factor release than comparable whole blood (p<0.03). These data suggest that non-platelet cellular components in platelet concentrates are important for proper platelet function, including thrombin generation, growth factor release and clot retraction.

[Autologous fat grafting in children].

PubMed

Baptista, C; Bertrand, B; Philandrianos, C; Degardin, N; Casanova, D

2016-10-01

Lipofilling or fat grafting transfer is defined as a technique of filling soft tissue by autologous fat grafting. The basic principle of lipofilling is based on a harvest of adipose tissue, followed by a reinjection after treatment. Lipofilling main objective is a volume defect filling, but also improving cutaneous trophicity. Lipofilling specificities among children is mainly based on these indications. Complications of autologous fat grafting among children are the same as those in adults: we distinguish short-term complications (intraoperative and perioperative) and the medium and long-term complications. The harvesting of fat tissue is the main limiting factor of the technique, due to low percentage of body fat of children. Indications of lipofilling among children may be specific or similar to those in adults. There are two types of indications: cosmetic, in which the aim of lipofilling is correcting a defect density, acquired (iatrogenic, post-traumatic scar) or malformation (otomandibular dysplasia, craniosynostosis, Parry Romberg syndrom, Poland syndrom, pectus excavatum…). The aim of functional indications is correcting a velar insufficiency or lagophthalmos. In the paediatric sector, lipofilling has become an alternative to the conventional techniques, by its reliability, safety, reproducibility, and good results. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Office-based Autologous Fat Injection Laryngoplasty for Vocal Process Granuloma.

PubMed

Hu, Hao-Chun; Hung, Yi-Ting; Lin, Shu-Yi; Chang, Shyue-Yih

2016-11-01

To present the outcomes of office-based autologous fat injection laryngoplasty for the treatment of vocal process granuloma in conjunction with glottic insufficiency. Retrospective chart review. This study included nine patients with vocal process granuloma in conjunction with glottic insufficiency who received autologous fat injection laryngoplasty. Videolaryngostroboscopic data, objective voice assessment, perceptual measurements of vocal quality, and subjective ratings of voice quality were examined before and after treatment. Of the nine patients, seven (78%) exhibited complete remission. The other two patients (22%) exhibited a partial response following the injection. In a subgroup of five patients who were refractory to antireflux and voice therapies, the resolution rate was 60%. Phonatory function presented significant improvements in jitter, noise-to-harmonic ratio, maximal phonation time, and asthenia. Videolaryngostroboscopic rating revealed significant improvements in closure phase ratio in the vibratory cycle. Autologous fat injection laryngoplasty can ameliorate glottic insufficiency and the resulting hyperfunctional behavior of the larynx. This therapy also encourages remission of vocal process granuloma and may represent an alternative treatment strategy. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

The role of autologous blood stem cells in support of high-dose therapy for multiple myeloma.

PubMed

Fermand, J P; Chevret, S; Levy, Y; Miclea, J M; Tsapis, A; Gerota, J; Benbunan, M; Brouet, J C

1992-04-01

During the last few years, high-dose therapy with hemopoietic stem cell support has become a well-admitted therapeutic option for young patients with MM. The role of allogeneic or autologous graft and of blood rather than bone marrow as the source of hemopoietic stem cells must be further investigated. Autologous PBSC transplantation has, however, both practical and theoretic advantages over allogeneic and autologous BMT: (1) It can be applied to most patients, especially if blood stem cells are collected early in the course of therapy. (2) It usually induces relatively rapid hematologic reconstitution. (3) In comparison with autologous BMT, it appears to minimize the hazard of the reinfusion of malignant cells.

Autologous Adipose-Derived Tissue Matrix Part I: Biologic Characteristics.

PubMed

Schendel, Stephen A

2017-10-01

Autologous collagen is an ideal soft tissue filler and may serve as a matrix for stem cell implantation and growth. Procurement of autologous collagen has been limited, though, secondary to a sufficient source. Liposuction is a widely performed and could be a source of autologous collagen. The amount of collagen and its composition in liposuctioned fat remains unknown. The purpose of this research was to characterize an adipose-derived tissue-based product created using ultrasonic cavitation and cryo-grinding. This study evaluated the cellular and protein composition of the final product. Fat was obtained from individuals undergoing routine liposuction and was processed by a 2 step process to obtain only the connective tissue. The tissue was then evaluated by scanning electronic microscope, Western blot analysis, and flow cytometry. Liposuctioned fat was obtained from 10 individuals with an average of 298 mL per subject. After processing an average of 1 mL of collagen matrix was obtained from each 100 mL of fat. Significant viable cell markers were present in descending order for adipocytes > CD90+ > CD105+ > CD45+ > CD19+ > CD144+ > CD34+. Western blot analysis showed collagen type II, III, IV, and other proteins. Scanning electronic microscope study showed a regular pattern of cross-linked, helical collagen. Additionally, vital staing demonstrated that the cells were still viable after processing. Collagen and cells can be easily obtained from liposuctioned fat by ultrasonic separation without alteration of the overall cellular composition of the tissue. Implantation results in new collagen and cellular growth. Collagen matrix with viable cells for autologous use can be obtained from liposuctioned fat and may provide long term results. 5. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Angiogenesis in rat uterine cicatrix after injection of autologous bone marrow mesenchymal stem cells.

PubMed

Maiborodin, I V; Yakimova, N V; Matveyeva, V A; Pekarev, O G; Maiborodina, E I; Pekareva, E O

2011-04-01

Results of injection of autologous bone marrow mesenchymal stem cells with transfected GFP gene into the rat uterine horn cicatrix were studied by light microscopy. Large groups of blood vessels with blood cells inside were seen after injection of autologous bone marrow cells into the cicatrix on the right horn, formed 2 months after its ligation; no groups of vessels of this kind were found in the cicatrix in the contralateral horn. Examination of unstained sections in reflected UV light showed sufficiently bright fluorescence in the endothelium and outer vascular membrane in the uterine horn cicatrix only on the side of injection. Hence, autologous mesenchymal stem cells injected into the cicatrix formed the blood vessels due to differentiation into endotheliocytes and pericytes. The expression of GFP gene not only in the vascular endothelium, but also in vascular outer membranes indicated that autologous mesenchymal stem cells differentiated in the endothelial and pericytic directions.

Supplementation of arachidonic acid rich oil in European sea bass juveniles (Dicentrarchus labrax) diets: Effects on leucocytes and plasma fatty acid profiles, selected immune parameters and circulating prostaglandins levels.

PubMed

Torrecillas, S; Román, L; Rivero-Ramírez, F; Caballero, M J; Pascual, C; Robaina, L; Izquierdo, M S; Acosta, F; Montero, D

2017-05-01

The main objective of this study was to assess the effects of graded levels of dietary arachidonic acid (ARA), supplemented from alternative sources, on fatty acid composition of plasma and head kidney leucocytes of European sea bass (Dicentrarchus labrax). For that purpose, sea bass juveniles were fed four diets containing graded levels of ARA as follows: 0.5% (ARA0.5), 1% (ARA1), 2% (ARA2) and 4% (ARA4) during 60 days. At the end of the feeding trial fatty acid profiles of plasma and head kidney leucocytes were analyzed. Besides, plasma prostaglandins levels, head kidney leucocytes respiratory burst activity; peroxidase activity and phagocytic index were assayed. Reducing dietary ARA levels below 1% markedly reduced European sea bass growth performance. However, fish fed diet ARA0.5 tried to compensate this dietary ARA deficiency by a selective deposition of ARA on plasma and head kidney leucocytes, reaching similar levels to those fish fed diet ARA1 after 60 days of feeding. Nevertheless, head kidney phagocytic capacity was reduced as dietary ARA content in relation not only to variations on membrane composition but also to changes on fish basal prostaglandins levels. Results obtained demonstrated the importance to supply the necessary quantity n-6 LC-PUFA, and not only n-3 LC-PUFA levels, in European sea bass diets, in relation to not only growth performance but also immune system function. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Clinical significance of autologous transplantation with hematopoietic stem cells in leukemia and solid tumors].

PubMed

Hinterberger, W; Adler, V; Bauer, K; Haberhauer, G; Habertheuer, K H; Höniger, S; Huber, K; Kier, P; Kittel, E; Ruckser, R

1995-01-01

Autologous Transplantation of hematopoietic tissue with frozen hematopoietic stem cells is increasingly used for leukemias and lymphomas, but also for some solid tumors. In the past, autotransplants have been performed with bone marrow as the source of hematopoietic stem cells. Circulating, blood derived hematopoietic stem cells, however, allow safe engraftment of all cell lines after supralethal chemo-radiotherapy. This survey describes the role of autologous stem cell transplantation in disorders that are currently in the center of clinical and scientific interest. This estimation is based on the proportion of protocols dealing with, and centering on, autologous stem cell transplantation in the context of treatment for leukemias and solid tumors ("Oncodisc", "PDQ").

Recovery of autologous sickle cells by hypotonic wash.

PubMed

Wilson, Emily; Kezeor, Kelly; Crosby, Monica

2018-01-01

It is important to isolate autologous red blood cells (RBCs) from transfused RBCs in samples from recently transfused patients to ensure that accurate serologic results are obtained. Typically, this isolation can be performed using methods that separate patient reticulocytes from transfused, older donor RBCs. Patients with sickle cell disease (SCD), however, characteristically have RBCs with altered membrane and morphological features, causing their RBCs to take on a sickle-shape appearance different from the biconcave disc-shape appearance of "normal" RBCs. These characteristics enable the use of hypotonic saline solution to lyse normal RBCs while allowing "sickle cells" to remain intact. Because many patients with SCD undergo frequent transfusions to treat their condition, the use of hypotonic saline solution provides a rapid method to obtain autologous RBCs for serologic testing from this patient population using standard laboratory equipment and supplies.

Autologous transplantation of the internal limiting membrane for refractory macular holes.

PubMed

Morizane, Yuki; Shiraga, Fumio; Kimura, Shuhei; Hosokawa, Mio; Shiode, Yusuke; Kawata, Tetsuhiro; Hosogi, Mika; Shirakata, Yukari; Okanouchi, Toshio

2014-04-01

To determine the effectiveness of autologous transplantation of the internal limiting membrane (ILM) for refractory macular holes. Prospective, interventional case series. Ten eyes of 10 consecutive patients who underwent autologous transplantation of the ILM for the treatment of refractory macular holes were studied. The primary diseases in these patients were large idiopathic macular holes that had existed for more than 1 year (4 eyes), a traumatic macular hole (1 eye), myopic foveoschisis (2 eyes), foveoschisis resulting from pit-macular syndrome (2 eyes), and proliferative diabetic retinopathy (1 eye). Apart from the 5 eyes with idiopathic or traumatic macular holes, macular holes developed in the other 5 eyes after initial vitrectomies with ILM removal. In all eyes, regular macular hole surgery failed to achieve closure. The main outcome measures used in this study were macular hole closure and best-corrected visual acuity (BCVA). Macular holes were closed successfully in 9 eyes (90%) after autologous transplantation of the ILM. The postoperative BCVAs were significantly better than the preoperative BCVAs (P = .007, paired t test). Postoperative BCVAs improved by more than 0.2 logarithm of the minimal angle of resolution units in 8 eyes (80%) and were unchanged in 2 eyes (20%). Although this is a pilot study, the results suggest that autologous transplantation of the ILM may contribute to improved anatomic and visual outcomes in the treatment of refractory macular holes and may warrant further investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Circulating microRNAs as Biomarkers for Detection of Autologous Blood Transfusion

PubMed Central

Leuenberger, Nicolas; Schumacher, Yorck Olaf; Pradervand, Sylvain; Sander, Thomas; Saugy, Martial; Pottgiesser, Torben

2013-01-01

MicroRNAs (miRNAs) are small non-coding RNAs that regulate various biological processes. Cell-free miRNAs measured in blood plasma have emerged as specific and sensitive markers of physiological processes and disease. In this study, we investigated whether circulating miRNAs can serve as biomarkers for the detection of autologous blood transfusion, a major doping technique that is still undetectable. Plasma miRNA levels were analyzed using high-throughput quantitative real-time PCR. Plasma samples were obtained before and at several time points after autologous blood transfusion (blood bag storage time 42 days) in 10 healthy subjects and 10 controls without transfusion. Other serum markers of erythropoiesis were determined in the same samples. Our results revealed a distinct change in the pattern of circulating miRNAs. Ten miRNAs were upregulated in transfusion samples compared with control samples. Among these, miR-30b, miR-30c, and miR-26b increased significantly and showed a 3.9-, 4.0-, and 3.0-fold change, respectively. The origin of these miRNAs was related to pulmonary and liver tissues. Erythropoietin (EPO) concentration decreased after blood reinfusion. A combination of miRNAs and EPO measurement in a mathematical model enhanced the efficiency of autologous transfusion detection through miRNA analysis. Therefore, our results lay the foundation for the development of miRNAs as novel blood-based biomarkers to detect autologous transfusion. PMID:23840438

Improvement of skin-graft survival after autologous transplantation of adipose-derived stem cells in rats.

PubMed

Zografou, A; Tsigris, C; Papadopoulos, O; Kavantzas, N; Patsouris, E; Donta, I; Perrea, D

2011-12-01

Skin grafts are frequently used for a variety of indications in plastic and reconstructive surgery. Their necrosis is a common complication, while different therapies have been proposed. Currently, adipose-derived stem cells (ASCs) hold great promise for their angiogenic potential and role during tissue repair. In this study, autologous transplantation of ASCs was used in skin grafts in rats to determine if it increases angiogenesis, skin-graft survival and wound healing. ASCs were isolated, cultured, labelled with fluorescent dye and injected under full-thickness skin grafts in 10 rats (group 1), while 10 others served as controls (group 2). Skin grafts were analysed after 1 week. Collagen's framework was assessed with Masson's trichrome stain and angiogenesis with von Willebrand factor (vWF) immunohistochemistry. In addition, immunohistochemical staining intensity of vascular endothelial growth factor (VEGF) and transforming growth factor b3 (TGFb3) was assessed in all grafts. Mean area of graft necrosis was significantly less in group 1 than in group 2 (6.12% vs. 32.62%, p<0.01). Statistically significant increase of microvessel density, collagen density, VEGF and TGFb3 expression was noted in group 1 compared with group 2 (all: p<0.01). These findings suggest that autologous ASCs transplantation increases full-thickness skin-graft survival and shows promise for use in skin-graft surgery. This might be both due to in situ differentiation of ASCs into endothelial cells and increased secretion by ASCs of growth factors, such as VEGF and TGFb3 that enhance angiogenesis and wound healing. Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

[Production of autologous keratinocytes for therapeutic purposes within a pharmaceutical company].

PubMed

Guillot, F L

2001-01-01

Because biotechnologies are growing and are becoming key players in the pharmaceutical industry scene, Genévrier Laboratories inaugurated in January 1998, a new department especially designed for the production of cultured cells as therapeutic agents. Meeting clinician therapeutic needs by providing autologous keratinocytes and chondrocytes in the near future, represents the primary aim of the Biotechnology department. Concrete cell-based products are already being used for the treatment of burns and cutaneous chronic wounds such as the EPIBASE graft, which corresponds to an epidermis sheet composed of cultured autologous keratinocytes.

[Penile augmentation and elongation using autologous dermal-fat strip grafting].

PubMed

Yang, Zhe; Li, Yang-qun; Tang, Yong; Chen, Wen; Li, Qiang; Zhou, Chuan-de; Zhao, Mu-xin; Hu, Chun-mei

2012-05-01

To investigate the effect of autologous dermal-fat strip grafting in penile augmentation and elongation. From May 2004 to December 2010, 24 patients underwent penile enhancement with free dermal-fat strip grafting. Through suprapubic incision, the superior suspensory ligament and part deep suspensory ligament are cutted off to lengthen the penis. The resulted dead space is filled with the autologous dermal-fat strip (6.0-9.5 cm in length, 1.2-1.5 cm in width and 0.6-0.8 cm in depth) to enhance the penis. Primary healing was achieved in 23 cases. Incisional fat liquefaction happened in one case which healed after dressing change. The penile appearance was satisfactory both at rest or erection. The penile length and circumference increased by 2.5-4.8 cm (average, 3.2 cm) and 1.8-3.0 cm (average, 2.4 cm), respectively. 18 patients were followed up for 3 months to 5 years. All the patients were satisfactory on the cosmetic and functional results. No complication happened. It is safe and effective for penile augmention and elongation with autologous dermal-fat strip grafting and disconnection of penile suspensory ligament.

Autologous fat transplantation: volumetric tools for estimation of volume survival. A systematic review.

PubMed

Herold, Christian; Ueberreiter, Klaus; Busche, Marc N; Vogt, Peter M

2013-04-01

Autologous fat transplantation has gained great recognition in aesthetic and reconstructive surgery. Two main aspects are of predominant importance for progress control after autologous fat transplantation to the breast: quantitative information about the rate of fat survival in terms of effective volume persistence and qualitative information about the breast tissue to exclude potential complications of autologous fat transplantation. There are several tools available for use in evaluating the rate of volume survival. They are extensively compared in this review. The anthropometric method, thermoplastic casts, and Archimedes' principle of water displacement are not up to date anymore because of major drawbacks, first and foremost being reduced reproducibility and exactness. They have been replaced by more exact and reproducible tools such as MRI volumetry or 3D body surface scans. For qualitative and quantitative progress control, MRI volumetry offers all the necessary information: evaluation of fat survival and diagnostically valuable imaging to exclude possible complications of autologous fat transplantation. For frequent follow-up, e.g., monthly volume analysis, repeated MRI exams would not be good for the patient and are not cost effective. In these cases, 3D surface imaging is a good tool and especially helpful in a private practice setting where fast data acquisition is needed. This tool also offers the possibility of simulating the results of autologous fat transplantation. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Manufacture of autologous serum eye drops for out-patient therapy : cooperation between ophthalmic clinic and transfusion medicine department].

PubMed

Dietrich, T; Weisbach, V; Seitz, B; Jacobi, C; Kruse, F E; Eckstein, R; Cursiefen, C

2008-11-01

Autologous serum eye drops are an important therapy option in severe ocular surface disorders and the therapeutic effectiveness has been demonstrated in many clinical studies. The production and use of autologous serum eye drops is strictly controlled by legal regulations in Germany: Both the German Medicines Act (AMG) and the Blood Transfusion Act regulate production, distribution and application, unless it is carried out by one person under controlled conditions in a hospital setting. In cooperation with the ophthalmic clinic and the department of transfusion medicine, a standard operating procedure (SOP) was developed and a license for production and delivery of autologous serum eye drops was obtained from the appropriate local authorities. The experiences of the first two years of practice were analyzed. By an interfaculty cooperation, the possibility of legal and feasible out-patient treatment with autologous eye drops has been established at the University Hospital Erlangen. From 07/2005 to 07/2007, there ware 240 prescriptions for autologous serum eye drops. Unexpectedly, a relatively high rate (3.3%) of patients with primarily unknown viral or bacterial infectious diseases were found, which were diagnosed during the screening. These patients had to be excluded from autologous serum eye drop therapy. The treatment with autologous serum eye drops in an out-patient setting is possible, when the infrastructure for manufacture and delivery is provided in accordance with existing regulations.

Isolation and partial characterization of melanoma-associated antigens identified by autologous antibody.

PubMed

Vlock, D R; Scalise, D; Meglin, N; Kirkwood, J M; Ballou, B

1988-06-01

The study of the autologous immune response to cancer avoids the difficulties encountered in the use of xenoantisera and may identify antigens of physiological relevance. However, the low titer and incidence of autologous antibody to melanoma have hampered further evaluation. By utilizing acid dissociation and ultrafiltration of serum, we have been able to augment the detectable autologous immune response to melanoma in the majority of patients studied. In autologous system Y-Mel 84:420, serum S150 demonstrated a rise in titer from 1:32 in native sera to 1:262,044 after dissociation. The antigen detected by S150 was found to be broadly represented on melanoma, glioma, renal cell carcinoma, neuroblastoma, and head and neck carcinoma cell lines. It did not react with bladder or colon carcinoma, fetal fibroblasts, pooled platelets, lymphocytes and red blood cells, or autologous cultured lymphocytes. Using polyacrylamide gel electrophoresis, S150 detects a 66,000-mol wt antigen in spent tissue culture media and serum ultrafiltrate. In cell lysate two bands between 20,000 and 30,000 mol wt are detected by S150. The 66,000-mol wt antigen is sensitive to trypsin digestion and but is resistant to pepsin and heat inactivation. Exposure of spent media to trypsin results in the development of a 24,000-mol wt band that appears to correspond to the antigen detected in the cell lysate. The difference between the antigens detected in the cell lysate as compared with spent media and serum ultrafiltrate may be due to degradation during cell lysis. We conclude that melanoma-associated antigens are present in the serum of patients with melanoma and are shed or secreted by their tumor cells.

Use of autologous and microsurgical breast reconstruction by U.S. plastic surgeons.

PubMed

Kulkarni, Anita R; Sears, Erika Davis; Atisha, Dunya M; Alderman, Amy K

2013-09-01

Concern exists that plastic surgeons are performing fewer autologous and microsurgical breast reconstructions, despite superior long-term outcomes. The authors describe the proportion of U.S. plastic surgeons performing these procedures and evaluate motivating factors and perceived barriers. A random national sample of American Society of Plastic Surgeons members was surveyed (n = 325; response rate, 76 percent). Surgeon and practice characteristics were assessed, and two multiple logistic regression models were created to evaluate factors associated with (1) high-volume autologous providers and (2) microsurgical providers. Qualitative assessments of motivating factors and barriers to microsurgery were also performed. Fewer than one-fifth of plastic surgeons perform autologous procedures for more than 50 percent of their breast cancer patients, and only one-quarter perform any microsurgical breast reconstruction. Independent predictors of a high-volume autologous practice include involvement with resident education (odds ratio, 2.57; 95 percent CI, 1.26 to 5.24) and a microsurgical fellowship (odds ratio, 2.09; 95 percent CI, 1.04 to 4.27). Predictors of microsurgical breast reconstruction include involvement with resident education (odds ratio, 6.8; 95 percent CI, 3.32 to 13.91), microsurgical fellowship (odds ratio, 2.4; 95 percent CI, 1.16 to 4.95), and high breast reconstruction volume (odds ratio, 6.68; 95 percent CI, 1.76 to 25.27). The primary motivator for microsurgery is superior outcomes, and the primary deterrents are time and reimbursement. The proportion of U.S. plastic surgeons with a high-volume autologous or microsurgical breast reconstruction practice is low. Involvement with resident education appears to facilitate both, whereas time constraints and reimbursement are primary deterrents. Future efforts should focus on improving the feasibility and accessibility of all types of breast reconstruction.

Autologous fat graft as treatment of post short stature surgical correction scars.

PubMed

Maione, Luca; Memeo, Antonio; Pedretti, Leopoldo; Verdoni, Fabio; Lisa, Andrea; Bandi, Valeria; Giannasi, Silvia; Vinci, Valeriano; Mambretti, Andrea; Klinger, Marco

2014-12-01

Surgical limb lengthening is undertaken to correct pathological short stature. Among the possible complications related to this procedure, painful and retractile scars are a cause for both functional and cosmetic concern. Our team has already shown the efficacy of autologous fat grafting in the treatment of scars with varying aetiology, so we decided to apply this technique to scars related to surgical correction of dwarfism. A prospective study was conducted to evaluate the efficacy of autologous fat grafting in the treatment of post-surgical scars in patients with short-limb dwarfism using durometer measurements and a modified patient and observer scar assessment scale (POSAS), to which was added a parameter to evaluate movement impairment. Between January 2009 and September 2012, 36 children (28 female and 8 male) who presented retractile and painful post-surgical scars came to our unit and were treated with autologous fat grafting. Preoperative and postoperative mean durometer measurements were analysed using the analysis of variance (ANOVA) test and POSAS parameters were studied using the Wilcoxon rank sum test. There was a statistically significant reduction in all durometer measurements (p-value <0.05) and in all but one of the POSAS parameters (p-value <0.05) following treatment with autologous fat grafting. Surgical procedures to camouflage scars on lower limbs are not often used as a first approach and non-surgical treatments often lead to unsatisfactory results. In contrast, our autologous fat grafting technique in the treatment of post-surgical scars has been shown to be a valuable option in patients with short-limb dwarfism. There was a reduction of skin hardness and a clinical improvement of all POSAS parameters in all patients treated. Moreover, the newly introduced POSAS parameter appears to be reliable and we recommend that it is included to give a more complete evaluation of patient perception. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effectiveness and safety of autologous fat grafting to the soft palate alone.

PubMed

Boneti, Cristiano; Ray, Peter D; Macklem, Elizabeth B; Kohanzadeh, Som; de la Torre, Jorge; Grant, John H

2015-06-01

Posterior pharyngeal augmentation is an accepted method of treating velopharyngeal insufficiency (VPI). Techniques using autologous fat harvest, preparation, and grafting are well described. Based on the complications from retropharyngeal injection, we performed augmentation of the nasal surface of the palate to reduce hypernasality with decreased risks. After Institutional Review Board approval, a chart review from 2010 to 2013 identified 46 patients with cleft palate, subjective and nasoendoscopic evidence of VPI treated with autologous fat grafting to the soft palate. Speech evaluation of velopharyngeal function was compared before and after autologous fat grafting. A total of 61 autologous fat grafting procedures were performed in 46 patients. The average age of the study population is 5.59 ± 2.05 years. The majority underwent a single procedure (32/46 or 69.6%), 13 of 46 patients (28.2%) had 2 fat grafting procedures and only 1 patient (2.2%) had 3 fat grafting procedures. The fat was injected primarily in the soft palate. The recorded volume of fat grafted averaged 2.4 ± 1.1 mL. Average operative time was 39 ± 12.55 minutes. There were no local or donor site complications. Four patients were lost to follow-up. Of 34 patients with adequate speech follow-up, including Pittsburgh Weighted Speech Scale (PWSS) assessment, the average preoperative score of 8.17 ± 3.59 was reduced to 5.17 ± 3.14 postoperatively. Although 26 of 34 patients (76.5%) had an improvement in their PWSS score, only 13 of 34 patients (38.23%) saw an improvement in their PWSS category. Autologous fat grafting to the soft palate is a safe operation with minimal risks. Speech outcomes are subjectively enhanced in the majority of patients, with a full PWSS category improvement seen in 40% of the cases. Patient selection criteria to optimize results are provided.

Human Neoplasms Elicit Multiple Specific Immune Responses in the Autologous Host

NASA Astrophysics Data System (ADS)

Sahin, Ugur; Tureci, Ozlem; Schmitt, Holger; Cochlovius, Bjorn; Johannes, Thomas; Schmits, Rudolf; Stenner, Frank; Luo, Guorong; Schobert, Ingrid; Pfreundschuh, Michael

1995-12-01

Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.

Autologous Dual-Tissue Transplantation for Osteochondral Repair

PubMed Central

Foldager, Casper Bindzus; Jensen, Jonas; Lind, Martin

2015-01-01

Background Numerous treatment methods for osteochondral repair have been implemented, including auto- and allogeneic osteochondral transplantations, combined bone and chondrocyte transplantations, and synthetic implants, but no gold standard treatment has been established. We present preliminary data on a combined autologous bone and cartilage chips: autologous dual-tissue transplantation (ADTT); an easily applicable, low-cost treatment option for osteochondral repair. The aim of this study was to investigate the early biological and clinical outcome of ADTT. Materials Eight patients (age 32 ± 7.5 years) suffering from osteochondritis dissecans (OCD) in the knee were enrolled. The OCD lesion was debrided and the osteochondral defect was filled with autologous bone, to a level at the base of the adjacent cartilage. Cartilage biopsies from the intercondylar notch were chipped and embedded within fibrin glue in the defect. Evaluation was performed using magnetic resonance imaging, computed tomography, and clinical scores, preoperative and 1 year postoperative. Results Cartilage tissue repair evaluated using MOCART score improved from 22.5 to 52.5 (P < 0.01). Computed tomography imaging demonstrated very good subchondral bone healing with all 8 patients having a bone filling of >80%. We found improvements 1 year postoperative in the International Knee Documentation Committee score (from 35.9 to 68.1, P < 0.01), Tegner score (from 2.6 to 4.7, P < 0.05), and Knee injury and Osteoarthritis Outcome Score pain, symptoms, sport/recreation and quality of life (P < 0.05). Conclusion Treatment of OCD with ADTT resulted in very good subchondral bone restoration and good cartilage repair. Significant improvements in patient reported outcome was found at 1 year postoperative. This study suggests ADTT as a promising, low-cost, treatment option for osteochondral injuries. PMID:26175862

Muscle-specific kinase-antibody-positive myasthenia gravis after autologous bone marrow transplantation.

PubMed

Grover, Kavita Mohindra; Sripathi, Naganand; Elias, Stanton Bernard

2012-03-01

A 44-year-old man presented with oculobulbar weakness approximately 5 years after autologous bone marrow transplantation (BMT). His workup led to the diagnosis of muscle-specific kinase-antibody-related myasthenia gravis (MG). There has been only one case report of muscle-specific kinase-antibody-positive MG after BMT, which was allogeneic. We report the first case of autologous BMT-associated MG with muscle-specific kinase antibody. The pathogenic mechanisms of immune dysregulation leading to MG after BMT are discussed.

Funding analysis of bilateral autologous free-flap breast reconstructions in Australia.

PubMed

Sinha, Shiba; Ruskin, Olivia; McCombe, David; Morrison, Wayne; Webb, Angela

2015-08-01

Bilateral breast reconstructions are being increasingly performed. Autologous free-flap reconstructions represent the gold standard for post-mastectomy breast reconstruction but are resource intensive. This study aims to investigate the difference between hospital reimbursement and true cost of bilateral autologous free-flap reconstructions. Retrospective analysis of patients who underwent bilateral autologous free-flap reconstructions at a single Australian tertiary referral centre was performed. Hospital reimbursement was determined from coding analysis. A true cost analysis was also performed. Comparisons were made considering the effect of timing, indication and complications of the procedure. Forty-six bilateral autologous free-flap procedures were performed (87 deep inferior epigastric perforators (DIEPs), four superficial inferior epigastric artery perforator flaps (SIEAs) and one muscle-sparing free transverse rectus abdominis myocutaneous flap (MS-TRAM)). The mean funding discrepancy between hospital reimbursement and actual cost was $12,137 ± $8539 (mean ± standard deviation (SD)) (n = 46). Twenty-four per cent (n = 11) of the cases had been coded inaccurately. If these cases were excluded from analysis, the mean funding discrepancy per case was $9168 ± $7453 (n = 35). Minor and major complications significantly increased the true cost and funding discrepancy (p = 0.02). Bilateral free-flap breast reconstructions performed in Australian public hospitals result in a funding discrepancy. Failure to be economically viable threatens the provision of this procedure in the public system. Plastic surgeons and hospital managers need to adopt measures in order to make these gold-standard procedures cost neutral. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

[Acquirement of autologous murine cytotoxic T lymphocytes via cryopreservation of lymphocytes].

PubMed

Wang, Lei; Peng, Na; Hu, Xiaoyan; Liang, Wentao; Liang, Kai; Peng, Guizhu

2016-11-01

Objective To evaluate the effects of cryopreservation on the proliferation and killing activity of lymphocytes, and explore a novel protocol of preparing autologous mouse cytotoxic T lymphocytes (CTLs). Methods Mononuclear cells derived from spleen (5.0×10 6 /mL) were cryopreserved in CELLBANKER2 for 6 days and recovered in water bath at 39DegreesCelsius. The fresh lymphocytes and post-cryopreservation lymphocytes were induced by CD3 mAb (100 ng/mL) and recombinant mouse interleukin 2 (rmIL-2, 100 ng/mL) to obtain cytokine-induced killer cells (CIKs). Dendritic cells (DCs) were co-cultured with fresh allogenic lymphocytes and post-cryopreservation autologous lymphocytes to obtain CTLs. The viable cells were counted by trypan blue staining; the percentages of CD3 + T cells and regulatory T cells (Tregs) were determined by flow cytometry; the levels of supernatant IFN-γ were detected through ELISA and the cytotoxicity was evaluated by lactate dehydrogenase (LDH) assay. Results The rate of viable lymphocytes declined to 78% after cryopreservation, and there were no significant differences in the percentages of CD3 + T cells and Tregs between pre-cryopreservation and post-cryopreservation. There were no significant differences in the proliferation of Tregs, the level of IFN-γ and the cytotoxicity between the fresh CIKs and cryopreservation CIKs, and the similar results were get between the autologous CTLs and allogenic CTLs. Conclusion The autologous CTLs acquired via cryopreservation of lymphocytes is equivalent to the allogenic CTLs with the similar proliferation and killing activity in vitro.

Leucocyte protein Trojan, a possible regulator of apoptosis.

PubMed

Petrov, Petar; Syrjänen, Riikka; Uchida, Tatsuya; Vainio, Olli

2017-02-01

Trojan is a leucocyte-specific protein, cloned from chicken embryonic thymocyte cDNA library. The molecule is a type I transmembrane protein with an extracellular CCP domain, followed by two FN3 domains. Its cytoplasmic tail is predicted to possess a MAPK docking and a PKA phosphorylation sites. Trojan has been proposed to have an anti-apoptotic role based on its differential expression on developing thymocyte subpopulations. Using a chicken cell line, our in vitro studies showed that upon apoptosis induction, Trojan expression rises dramatically on the surface of surviving cells and gradually decreases towards its normal levels as cells recover. When sorted based on their expression levels of Trojan, cells with high expression appeared less susceptible to apoptotic induction than those bearing no or low levels of Trojan on their surface. The mechanism by which the molecule exerts its function is yet to be discovered. We found that cells overexpressing Trojan from a cDNA plasmid show elevated steady-state levels of intracellular calcium, suggesting the molecule is able to transmit cytoplasmic signals. The mechanistic nature of Trojan-induced signalling is a target of future investigation. In this article, we conducted a series of experiments that suggest Trojan as an anti-apoptotic regulator. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Bio-artificial pleura using an autologous dermal fibroblast sheet

NASA Astrophysics Data System (ADS)

Kanzaki, Masato; Takagi, Ryo; Washio, Kaoru; Kokubo, Mami; Yamato, Masayuki

2017-10-01

Air leaks (ALs) are observed after pulmonary resections, and without proper treatment, can produce severe complications. AL prevention is a critical objective for managing patients after pulmonary resection. This study applied autologous dermal fibroblast sheets (DFS) to close ALs. For sealing ALs in a 44-year-old male human patient with multiple bullae, a 5 × 15-mm section of skin was surgically excised. From this skin specimen, primary dermal fibroblasts were isolated and cultured for 4 weeks to produce DFSs that were harvested after a 10-day culture. ALs were completely sealed using surgical placement of these autologous DFSs. DFS were found to be a durable long-term AL sealant, exhibiting requisite flexibility, elasticity, durability, biocompatibility, and usability, resulting reliable AL closure. DFS should prove to be an extremely useful tissue-engineered pleura substitute.

Autologous whole blood versus corticosteroid local injection in treatment of plantar fasciitis: A randomized, controlled multicenter clinical trial.

PubMed

Karimzadeh, Afshin; Raeissadat, Seyed Ahmad; Erfani Fam, Saleh; Sedighipour, Leyla; Babaei-Ghazani, Arash

2017-03-01

Plantar fasciitis is the most common cause of heel pain. Local injection modalities are among treatment options in patients with resistant pain. The aim of the present study was to evaluate the effect of local autologous whole blood compared with corticosteroid local injection in treatment of plantar fasciitis. In this randomized controlled multicenter study, 36 patients with chronic plantar fasciitis were recruited. Patients were allocated randomly into three treatment groups: local autologous blood, local corticosteroid injection, and control groups receiving no injection. Patients were assessed with visual analog scale (VAS), pressure pain threshold (PPT), and plantar fasciitis pain/disability scale (PFPS) before treatment, as well as 4 and 12 weeks post therapy. Variables of pain and function improved significantly in both corticosteroid and autologous blood groups compared to control group. At 4 weeks following treatment, patients in corticosteroid group had significantly lower levels of pain than patients in autologous blood and control groups (higher PPT level, lower PFPS, and VAS). After 12 weeks of treatment, both corticosteroid and autologous blood groups had lower average levels of pain than control group. The corticosteroid group showed an early sharp and then more gradual improvement in pain scores, but autologous blood group had a steady gradual drop in pain. Autologous whole blood and corticosteroid local injection can both be considered as effective methods in the treatment of chronic plantar fasciitis. These treatments decrease pain and significantly improve function compared to no treatment.

Autologous dental pulp stem cells in periodontal regeneration: a case report.

PubMed

Aimetti, Mario; Ferrarotti, Francesco; Cricenti, Luca; Mariani, Giulia Maria; Romano, Federica

2014-01-01

Histologic findings in animal models suggest that the application of dental pulp stem cells (DPSCs) may promote periodontal regeneration in infrabony defects. This case report describes the clinical and radiographic regenerative potential of autologous DPSCs in the treatment of human noncontained intraosseous defects. A chronic periodontitis patient with one vital third molar requiring extraction was surgically treated. The third molar was extracted and used as an autologous DPSCs source to regenerate the infrabony defect on the mandibular right second premolar. At the 1-year examination, the defect was completely filled with bonelike tissue as confirmed through the reentry procedure.

Development and testing of a new disposable sterile device for labelling white blood cells.

PubMed

Signore, A; Glaudemans, A W J M; Malviya, G; Lazzeri, E; Prandini, N; Viglietti, A L; De Vries, E F J; Dierckx, R A J O

2012-08-01

White blood cell (WBC) labelling requires isolation of cells from patient's blood under sterile conditions using sterile materials, buffers and disposables under good manufacturing practice (GMP) conditions. Till now, this limited the use of white blood cell scintigraphy (WBC-S) only to well equipped laboratories with trained personnel. We invented, developed and tested a disposable, sterile, closed device for blood manipulation, WBC purification and radionuclide labelling without exposing patient's blood and the operator to contamination risks. This device prototype and a final industrialized device (Leukokit®) were tested for WBC labelling and compared to standard procedure. Leukokit® was also tested in an international multi-centre study for easiness of WBC purification and labelling. On the device prototype we tested in parallel, with blood samples from 7 volunteers, the labelling procedure compared to the standard procedure of the International Society of Radiolabeled Blood Elements (ISORBE) consensus protocol with respect to cell recovery, labelling efficiency (LE), cell viability (Trypan Blue test) and sterility (haemoculture). On the final Leukokit® we tested the biocompatibility of all components, and again the LE, erythro-sedimentation rate, cell viability, sterility and apyrogenicity. ACD-A, HES and PBS provided by Leukokit® were also compared to Heparin, Dextran and autologous plasma, respectively. In 4 samples, we tested the chemotactic activity of purified WBC against 1 mg/ml of lipopolysaccharide (LPS) and chemotaxis of 99mTc-HMPAO-labelled WBC (925 MBq) was compared to that of unlabelled cells. For the multi-centre study, 70 labellings were performed with the Leukokit® by 9 expert operators and 3 beginners from five centers using blood from both patients and volunteers. Finally, Media-Fill tests were performed by 3 operators on two different days (11 procedures) by replacing blood and kit reagents with bacterial culture media (Tryptic Soy Broth

Targeted preoperative autologous blood donation in total knee arthroplasty reduces the need for postoperative transfusion.

PubMed

Bou Monsef, Jad; Buckup, Johannes; Mayman, David; Marx, Robert; Ranawat, Amar; Boettner, Friedrich

2013-10-01

Preoperative donation of autologous blood has been widely used to minimize the potential risk of allogeneic transfusions in total knee arthroplasty. A previous study from our center revealed that preoperative autologous donation reduces the allogeneic blood exposure for anemic patients but has no effect for non-anemic patients. The current study investigates the impact of a targeted blood donation protocol on overall transfusion rates and the incidence of allogeneic blood transfusions. Prospectively, 372 patients undergoing 425 unilateral primary knee replacements were preoperatively screened by the Blood Preservation Center between 2009 and 2012. Anemic patients with a hemoglobin level less than 13.5 g/dL were advised to donate blood, while non-anemic patients did not donate. Non-anemic patients who did not donate blood required allogeneic blood transfusions in 5.9% of the patients. The overall rate of allogeneic transfusion was significantly lower for anemic patients who donated autologous blood (group A, 9%) than those who did not donate (group B, 33%; p < 0.001). Donating autologous blood did increase the overall transfusion rate of anemic patients to 0.84 per patient in group A compared to 0.41 per patient in group B (p < 0.001). This investigation confirms that abandoning preoperative autologous blood donation for non-anemic patients does not increase allogeneic blood transfusion rates but significantly lowers overall transfusion rates.

High Rate of Induction of Human Autologous Cytotoxic T Lymphocytes against Renal Carcinoma Cells Cultured with an Interleukin Cocktail

PubMed Central

Liu, Shu Qin; Kawai, Koji; Shiraiwa, Hiroshi; Hayashi, Hitoshi; Akaza, Hideyuki; Hashizaki, Kazuko; Shiba, Reiko; Saijo, Kaoru

1998-01-01

A high rate of induction (9 of 10 cases) of human autologous cytotoxic T lymphocytes (CTL) was achieved in vitro from peripheral blood mononuclear cells of renal carcinoma patients by applying an interleukin (IL)‐cocktail consisting of IL‐1, ‐2, ‐4, and ‐6. The CTL specifically lysed their own target carcinoma cells within 24 h but did not kill neighboring autologous normal kidney cells or allogeneic renal cancer cell lines. In the case of TUHR4TKB, for which autologous CTL were not induced, no expression of MHC class‐I molecules was observed on the surface of these carcinoma cells, although they were sensitive to autologous natural killer cells. The results imply that adoptive immunotherapy for metastasized renal carcinoma will be feasible with autologous CTL in combination with natural killer cells. PMID:9914789

The production of arthritis in the guinea-pig by intra-articular reaction between lymphokines and inflammatory leucocytes.

PubMed Central

Limb, G. A.; Brown, K. A.; Wolstencroft, R. A.; Ellis, B. A.; Dumonde, D. C.

1989-01-01

A single intra-articular injection of lymphokine into the guinea-pig knee joint resulted in a sequence of changes in joint architecture whose histopathological features resembled that of an acute inflammatory reaction progressing to a chronic state. At 24 h there was a mild hyperplasia and hypertrophy of the synovium with intense polymorphonuclear leucocyte infiltration. At 72 h, the synovium was heavily infiltrated with diffuse and focal aggregations of mononuclear cells; erosion of cartilage and bone by synovial pannus was accompanied by a subsynovial fibrosis. By 1 week, leucocytic infiltration of the synovium had decreased markedly although the erosion and fibrosis persisted. However, when lymphokine was injected together with oil-elicited peritoneal exudate cells a more intense arthritis ensued: at 72 h synovial pannus was prominently eroding bone and this was accompanied by the appearance of multinucleate cells resembling osteoclasts in the zone of erosion. These features were shown to resemble closely the histopathology of experimental allergic arthritis in the guinea-pig, in contrast to the lesser severity of synovitis resulting from the adoptive cellular transfer of delayed hypersensitivity into the joint. The results indicate that lymphokines may play a role in the induction of experimental allergic arthritis by recruiting and activating cells involved in chronic inflammation. Images Fig. 1 Fig. 2 Fig. 3 PMID:2765396

Familial acquired thrombotic thrombocytopenic purpura in siblings - no immunogenetic link with associated human leucocyte antigens.

PubMed

Gödel, Philipp; Fischer, Julia; Scheid, Christoph; Gathof, Birgit S; Wolf, Jürgen; Rybniker, Jan

2017-03-01

Acquired immunoglobulin G (IgG)-mediated thrombotic thrombocytopenic purpura (TTP) has not yet been described in non-twin siblings. We report two cases of acquired TTP in Caucasian sisters with inactive ADAMTS13 metalloprotease due to ADAMTS13 autoantibodies suggesting a role of genetic determinants in this life-threatening disease. However, human leucocyte antigen (HLA) class II types presumably associated with acquired TTP were not identified in the patients, indicating that HLA class II typing may not be useful in acquired TTP risk assessment of family members. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Evaluation of the mutagenicity of detergents by tests on bacteria, plant cells and human leucocytes.].

PubMed

Feretti, Donatella; Pedrazzani, Roberta; Ceretti, Elisabetta; Zerbini, Ilaria; Gozio, Eleonora; Belotti, Caterina; Alias, Carlotta; Donato, Francesco; Gelatti, Umberto

2009-01-01

The aim of this study was to evaluate the mutagenicity of several traditional detergents and that of newer more biodegradable detergents, by using a bacterial test (Ames test), a plant cell test (Allium cepa micronuclei test) and a human leucocyte test (Comet test). All tests were conducted using a wide range of doses (1-2000 mg/l). None of the examined detergents induced mutations in S.typhimurium. One traditional detergent showed a genotoxic effect with the A. cepa test, while all newer detergents and one traditional detergent were shown by the Comet test to be capable of inducing DNA damage.

Gene therapy with autologous, interleukin 2-secreting tumor cells in patients with malignant melanoma.

PubMed

Palmer, K; Moore, J; Everard, M; Harris, J D; Rodgers, S; Rees, R C; Murray, A K; Mascari, R; Kirkwood, J; Riches, P G; Fisher, C; Thomas, J M; Harries, M; Johnston, S R; Collins, M K; Gore, M E

1999-05-20

We vaccinated metastatic melanoma patients with irradiated, autologous melanoma cells genetically engineered to secrete interleukin 2 (IL-2) to investigate whether an anti-tumor immune response would be induced. Melanoma cell cultures were established from surgical specimens and were engineered to secrete IL-2 by infection with recombinant retrovirus. Twelve patients were vaccinated subcutaneously one, two, or three times with approximately 10(7) irradiated, autologous, IL-2-secreting tumor cells. Treatment was well tolerated, with local reactions at 11 of 24 injection sites and minor systemic symptoms of fever and headache after 6 injections. One patient developed anti-tumor DTH after the first vaccination and showed an increased response after the second vaccination. Anti-autologous tumor CTLs could be detected prevaccination in the peripheral blood of seven patients and their activity increased after vaccination in four patients. No UICC-defined clinical responses were seen, but three patients had stable disease for 7-15 months, one of whom has not yet progressed (15+ months). Thus, patient vaccination with autologous, genetically engineered tumor cells is feasible and safe. Anti-tumor DTH and CTLs can be induced in some patients with such a vaccine.

Imaging infection with 18F-FDG-labeled leukocyte PET/CT: initial experience in 21 patients.

PubMed

Dumarey, Nicolas; Egrise, Dominique; Blocklet, Didier; Stallenberg, Bernard; Remmelink, Myriam; del Marmol, Véronique; Van Simaeys, Gaëtan; Jacobs, Frédérique; Goldman, Serge

2006-04-01

The aim of this study was to assess the feasibility and the potential role of PET/CT with (18)F-FDG-labeled autologous leukocytes in the diagnosis and localization of infectious lesions. Twenty-one consecutive patients with suspected or documented infection were prospectively evaluated with whole-body PET/CT 3 h after injection of autologous (18)F-FDG-labeled leukocytes. Two experienced nuclear medicine physicians who were unaware of the clinical end-diagnosis reviewed all PET/CT studies. A visual score (0-3)-according to uptake intensity-was used to assess studies. The results of PET/CT with (18)F-FDG-labeled white blood cell ((18)F-FDG-WBC) assessment were compared with histologic or biologic diagnosis in 15 patients and with clinical end-diagnosis after complete clinical work-up in 6 patients. Nine patients had fever of unknown etiology, 6 patients had documented infection but with unknown extension of the infectious disease, 4 patients had a documented infection with unfavorable evolution, and 2 patients had a documented infection with known extension. The best trade-off between sensitivity and specificity was obtained when a visual score of >or=2 was chosen to identify increased tracer uptake as infection. With this threshold, sensitivity, specificity, and accuracy were each 86% on a patient-per-patient basis and 91%, 85%, and 90% on a lesion-per-lesion basis. In this small group of patients, the absence of areas with increased WBC uptake on WBC PET/CT had a 100% negative predictive value. Hybrid (18)F-FDG-WBC PET/CT was found to have a high sensitivity and specificity for the diagnosis of infection. It located infectious lesions with a high precision. In this small series, absence of areas with increased uptake virtually ruled out the presence of infection. (18)F-FDG-WBC PET/CT for infection detection deserves further investigation in a larger prospective series.

Post-operative course of coronary artery bypass surgery patients who pre-donate autologous blood.

PubMed

Jovin, Ion S; Stelzig, Georg; Strelitz, Joachim C; Taborski, Uwe; Jovin, Angelika; Heidinger, Kathrin; Klövekorn, Wolf-Peter; Müller-Berghaus, Gert

2003-12-01

Pre-operative autologous blood donation is used to reduce the need of allogeneic blood in patients undergoing coronary bypass surgery operations, but it is not clear what impact the blood donation has on the post-operative course of these patients. We studied the post-operative course of 210 patients who pre-donated autologous blood before their coronary bypass operation (donors) and of 67 patients who were eligible to pre-donate but did not (controls). The clinical variables and the technical operative parameters of the patients in the two groups were similar. There was no significant difference between the duration of assisted ventilation post-operatively (756 +/- 197 vs. 802 +/- 395 min; P=0.54) or length of stay in the intensive care unit (1.8 +/- 1.1 vs. 1.7 +/- 0.9 days; P=0.52) of the two groups. The number of autologous units of packed red cells and of fresh frozen plasma (FFP) received by the donors was significantly higher than the number of units of allogeneic packed red cells (1.5 +/- 0.9 vs. 0.3 +/- 0.9; P=0.001) and the units of homologous FFP received by the controls (2.3 +/- 0.8 vs. 0.6 +/- 1; P=0.001). We found no evidence that autologous blood donation exerted a negative influence on the post-operative course of patients undergoing coronary bypass surgery. Patients who pre-donated blood received no allogeneic blood products, but the number of autologous blood products received by donors was higher than the number of blood products received by patients who did not pre-donate.

Cytotoxic T cell clones isolated from ovarian tumor-infiltrating lymphocytes recognize multiple antigenic epitopes on autologous tumor cells.

PubMed

Ioannides, C G; Freedman, R S; Platsoucas, C D; Rashed, S; Kim, Y P

1991-03-01

CTL clones were developed from tumor infiltrating lymphocytes (TIL) from the ascites of a patient with ovarian carcinoma by coculture of TIL with autologous tumor cells and subsequent cloning in the presence of autologous tumor cells. These CTL clones expressed preferential cytolytic activity against autologous tumor cells but not against allogeneic ovarian tumor cells and the NK-sensitive cell line K562. The cytolytic activity of these CTL against autologous tumors was inhibited by anti-TCR (WT31 mAb), anti-HLA class I, and anti-CD3 mAb but not by the NK function antibody Leu 11b. Cloning of the autologous tumor cells in vitro revealed that the CTL clones of the ovarian TIL expressed differential abilities to lyse autologous tumor cell clones. The specificity analysis of these autologous tumor specific CTL suggested that they recognize several antigenic determinants present on the ovarian tumor cells. Our results indicate the presence of at least three antigenic epitopes on the tumor cells (designated OVA-1A, OVA-1B, and OVA-1C), one of which (OVA-1C) is unstable. These determinants are present either simultaneously or separately, and six types of ovarian clones can be distinguished on the basis of their expression. These results indicate that CTL of the TIL detect intratumor antigenic heterogeneity. The novel heterogeneity identified within the ovarian tumor cells in this report may be of significance for understanding cellular immunity in ovarian cancer and developing adoptive specific immunotherapeutic approaches in ovarian cancer.

Computer-assisted selection of donor sites for autologous grafts

NASA Astrophysics Data System (ADS)

Krol, Zdzislaw; Zeilhofer, Hans-Florian U.; Sader, Robert; Hoffmann, Karl-Heinz; Gerhardt, Paul; Horch, Hans-Henning

1997-05-01

A new method is proposed for a precise planning of autologous bone grafts in cranio- and maxillofacial surgery. In patients with defects of the facial skeleton, autologous bone transplants can be harvested from various donor sites in the body. The preselection of a donor site depends i.a. on the morphological fit of the available bone mass and the shape of the part that is to be transplanted. A thorough planning and simulation of the surgical intervention based on 3D CT studies leads to a geometrical description and the volumetric characterization of the bone part to be resected and transplanted. Both, an optimal fit and a minimal lesion of the donor site are guidelines in this process. We use surface similarity and voxel similarity measures in order to select the optimal donor region for an individually designed transplant.

Reconstruction of acquired sub-total ear defects with autologous costal cartilage.

PubMed

Harris, P A; Ladhani, K; Das-Gupta, R; Gault, D T

1999-06-01

Acquired sub-total ear defects are common and challenging to reconstruct. We report the use of an autologous costal cartilage framework to reconstruct sub-total defects involving all anatomical regions of the ear. Twenty-eight partially damaged ears in 27 patients were reconstructed with this technique. The defects resulted from bites (14), road traffic accidents (five), burns (four), iatrogenic causes (four) and chondritis following minor trauma (one). Computerised image analysis revealed a median of 31% (range 13-72%) ear loss. An autologous costal cartilage framework was fashioned in all cases. If adequate local skin was available, this was draped over the framework, but in nine cases preliminary tissue expansion was used and in a further three cases with significant scarring, the framework was covered with a temporoparietal fascial flap. Clinical assessment after ear reconstruction was undertaken, scoring for symmetry, the helical rim, the antihelical fold, the lobe position and a 'natural look' to produce a four-point scale; 11 were excellent, 12 were good, two were fair and three were poor. Our experience suggests that formal delayed reconstruction with autologous costal cartilage is to be recommended when managing acquired, sub-total ear deformity.

Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

PubMed Central

Hayashi, Takuya; Wakao, Shohei; Kitada, Masaaki; Ose, Takayuki; Watabe, Hiroshi; Kuroda, Yasumasa; Mitsunaga, Kanae; Matsuse, Dai; Shigemoto, Taeko; Ito, Akihito; Ikeda, Hironobu; Fukuyama, Hidenao; Onoe, Hirotaka; Tabata, Yasuhiko; Dezawa, Mari

2012-01-01

A cell-based therapy for the replacement of dopaminergic neurons has been a long-term goal in Parkinson’s disease research. Here, we show that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells (MSCs) leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques. Differentiated MSCs expressed markers of A9 dopaminergic neurons and released dopamine after depolarization in vitro. The differentiated autologous cells were engrafted in the affected portion of the striatum. Animals that received transplants showed modest and gradual improvements in motor behaviors. Positron emission tomography (PET) using [11C]-CFT, a ligand for the dopamine transporter (DAT), revealed a dramatic increase in DAT expression, with a subsequent exponential decline over a period of 7 months. Kinetic analysis of the PET findings revealed that DAT expression remained above baseline levels for over 7 months. Immunohistochemical evaluations at 9 months consistently demonstrated the existence of cells positive for DAT and other A9 dopaminergic neuron markers in the engrafted striatum. These data suggest that transplantation of differentiated autologous MSCs may represent a safe and effective cell therapy for Parkinson’s disease. PMID:23202734

Single-Stage Cartilage Repair Using Platelet-Rich Fibrin Scaffolds With Autologous Cartilaginous Grafts.

PubMed

Wong, Chin-Chean; Chen, Chih-Hwa; Chan, Wing P; Chiu, Li-Hsuan; Ho, Wei-Pin; Hsieh, Fon-Jou; Chen, You-Tzung; Yang, Tsung-Lin

2017-11-01

To avoid complicated procedures requiring in vitro chondrocyte expansion for cartilage repair, the development of a culture-free, 1-stage approach combining platelet-rich fibrin (PRF) and autologous cartilage grafts may be the solution. To develop a feasible 1-step procedure to combine PRF and autologous cartilage grafts for articular chondral defects. Controlled laboratory study Methods: The chemotactic effects of PRF on chondrocytes harvested from the primary culture of rabbit cartilage were evaluated in vitro and ex vivo. The rabbit chondrocytes were cultured with different concentrations of PRF media and evaluated for their cell proliferation, chondrogenic gene expression, cell viability, and extracellular matrix synthesis abilities. For the in vivo study, the chondral defects were created on established animal models of rabbits. The gross anatomy, histology, and objective scores were evaluated to validate the treatment results. PRF improved the chemotaxis, proliferation, and viability of the cultured chondrocytes. The gene expression of the chondrogenic markers, including type II collagen and aggrecan, revealed that PRF induced the chondrogenic differentiation of cultured chondrocytes. PRF increased the formation and deposition of the cartilaginous matrix produced by cultured chondrocytes. The efficacy of PRF on cell viability was comparable with that of fetal bovine serum. In animal disease models, morphologic, histological, and objectively quantitative evaluation demonstrated that PRF combined with cartilage granules was feasible in facilitating chondral repair. PRF enhances the migration, proliferation, viability, and differentiation of chondrocytes, thus showing an appealing capacity for cartilage repair. The data altogether provide evidence to confirm the feasibility of 1-stage, culture-free method of combining PRF and autologous cartilage graft for repairing articular chondral defects. The single-stage, culture-free method of combining PRF and autologous

19F-perfluorocarbon-labeled human peripheral blood mononuclear cells can be detected in vivo using clinical MRI parameters in a therapeutic cell setting.

PubMed

Fink, Corby; Gaudet, Jeffrey M; Fox, Matthew S; Bhatt, Shashank; Viswanathan, Sowmya; Smith, Michael; Chin, Joseph; Foster, Paula J; Dekaban, Gregory A

2018-01-12

A 19 Fluorine ( 19 F) perfluorocarbon cell labeling agent, when employed with an appropriate cellular MRI protocol, allows for in vivo cell tracking. 19 F cellular MRI can be used to non-invasively assess the location and persistence of cell-based cancer vaccines and other cell-based therapies. This study was designed to determine the feasibility of labeling and tracking peripheral blood mononuclear cells (PBMC), a heterogeneous cell population. Under GMP-compliant conditions human PBMC were labeled with a 19 F-based MRI cell-labeling agent in a manner safe for autologous re-injection. Greater than 99% of PBMC labeled with the 19 F cell-labeling agent without affecting functionality or affecting viability. The 19 F-labeled PBMC were detected in vivo in a mouse model at the injection site and in a draining lymph node. A clinical cellular MR protocol was optimized for the detection of PBMC injected both at the surface of a porcine shank and at a depth of 1.2 cm, equivalent to depth of a human lymph node, using a dual 1 H/ 19 F dual switchable surface radio frequency coil. This study demonstrates it is feasible to label and track 19 F-labeled PBMC using clinical MRI protocols. Thus, 19 F cellular MRI represents a non-invasive imaging technique suitable to assess the effectiveness of cell-based cancer vaccines.

Restricted dog leucocyte antigen (DLA) class II haplotypes and genotypes in Beagles.

PubMed

Soutter, Francesca; Kennedy, Lorna J; Ollier, William E R; Solano-Gallego, Laia; Catchpole, Brian

2015-03-01

Beagles are commonly used in vaccine trials as part of the regulatory approval process. Genetic restriction within this breed and the impact this might have on vaccine responses are rarely considered. This study was designed to characterise diversity of dog leucocyte antigen (DLA) class II genes in a breeding colony of laboratory Beagles, whose offspring are used in vaccine studies. DLA haplotypes were determined by PCR and sequence-based typing from genomic DNA extracted from blood. Breeding colony Beagles had significantly different DLA haplotype frequencies in comparison with pet Beagles and both groups showed limited DLA diversity. Restricted DLA class II genetic variability within Beagles might result in selective antigen presentation and vaccine responses that are not necessarily representative of those seen in other dog breeds. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effectiveness of Autologous Fat Grafting in Adherent Scars: Results Obtained by a Comprehensive Scar Evaluation Protocol.

PubMed

Jaspers, Mariëlle E H; Brouwer, Katrien M; van Trier, Antoine J M; Groot, Marloes L; Middelkoop, Esther; van Zuijlen, Paul P M

2017-01-01

Nowadays, patients normally survive severe traumas such as burn injuries and necrotizing fasciitis. Large skin defects can be closed but the scars remain. Scars may become adherent to underlying structures when the subcutical fat layer is damaged. Autologous fat grafting provides the possibility of reconstructing a functional sliding layer underneath the scar. Autologous fat grafting is becoming increasingly popular for scar treatment, although large studies using validated evaluation tools are lacking. The authors therefore objectified the effectiveness of single-treatment autologous fat grafting on scar pliability using validated scar measurement tools. Forty patients with adherent scars receiving single-treatment autologous fat grafting were measured preoperatively and at 3-month follow-up. The primary outcome parameter was scar pliability, measured using the Cutometer. Scar quality was also evaluated by the Patient and Observer Scar Assessment Scale and the DSM II ColorMeter. To prevent selection bias, measurements were performed following a standardized algorithm. The Cutometer parameters elasticity and maximal extension improved 22.5 percent (p < 0.001) and 15.6 percent (p = 0.001), respectively. Total Patient and Observer Scar Assessment Scale scores improved from 3.6 to 2.9 on the observer scale, and from 5.1 to 3.8 on the patient scale (both p < 0.001). Color differences between the scar and normal skin remained unaltered. For the first time, the effect of autologous fat grafting on functional scar parameters was ascertained using a comprehensive scar evaluation protocol. The improved scar pliability supports the authors' hypothesis that the function of the subcutis can be restored to a certain extent by single-treatment autologous fat grafting. Therapeutic, IV.

Differential patterns of endothelial and leucocyte activation in 'typhus-like' illnesses in Laos and Thailand.

PubMed

Paris, D H; Jenjaroen, K; Blacksell, S D; Phetsouvanh, R; Wuthiekanun, V; Newton, P N; Day, N P J; Turner, G D H

2008-07-01

Scrub typhus is responsible for a large proportion of undifferentiated fevers in south-east Asia. The cellular tropism and pathophysiology of the causative agent, Orientia tsutsugamushi, remain poorly understood. We measured endothelial and leucocyte activation by soluble cell adhesion molecule enzyme-linked immunosorbent assays in 242 Lao and Thai patients with scrub or murine typhus, leptospirosis, dengue, typhoid and uncomplicated falciparum malaria on admission to hospital. Soluble E-selectin (sE-selectin) levels were lowest in dengue, sL-selectin highest in scrub typhus with a high sE-selectin to sL-selectin ratio in leptospirosis patients. In scrub typhus patients elevated sL-selectin levels correlated with the duration of skin rash (P = 0.03) and the presence of eschar (P = 0.03), elevated white blood cell (WBC) count (P = 0.007), elevated lymphocyte (P = 0.007) and neutrophil counts (P = 0.015) and elevated levels of sE-selectin correlated with the duration of illness before admission (P = 0.03), the presence of lymphadenopathy (P = 0.033) and eschar (P = 0.03), elevated WBC (P = 0.005) and neutrophil counts (P = 0.0003). In comparison, soluble selectin levels in murine typhus patients correlated only with elevated WBC counts (P = 0.03 for sE-selectin and sL-selectin). Soluble intercellular adhesion molecule-1 and soluble vascular adhesion molecule-1 levels were not associated significantly with any clinical parameters in scrub or murine typhus patients. The data presented suggest mononuclear cell activation in scrub typhus. As adhesion molecules direct leucocyte migration and induce inflammatory and immune responses, this may represent O. tsutsugamushi tropism during early dissemination, or local immune activation within the eschar.

Detecting autologous blood transfusions: a comparison of three passport approaches and four blood markers.

PubMed

Mørkeberg, J; Sharpe, K; Belhage, B; Damsgaard, R; Schmidt, W; Prommer, N; Gore, C J; Ashenden, M J

2011-04-01

Blood passport has been suggested as an indirect tool to detect various kinds of blood manipulations. Autologous blood transfusions are currently undetectable, and the objective of this study was to examine the sensitivities of different blood markers and blood passport approaches in order to determine the best approach to detect autologous blood transfusions. Twenty-nine subjects were transfused with either one (n=8) or three (n=21) bags of autologous blood. Hemoglobin concentration ([Hb]), percentage of reticulocytes (%ret) and hemoglobin mass (Hbmass) were measured 1 day before reinfusion and six times after reinfusion. The sensitivity and specificity of a novel marker, Hbmr (based on Hbmass and %ret), was evaluated together with [Hb], Hbmass and OFF-hr by different passport methods. Our novel Hbmr marker showed superior sensitivity in detecting the highest dosage of transfused blood, with OFF-hr showing equal or superior sensitivities at lower dosages. Hbmr and OFF-hr showed superior but equal sensitivities from 1 to 4 weeks after transfusion compared with [Hb] and Hbmass, with Hbmass being the only tenable prospect to detect acute transfusions. Because autologous blood transfusions can be an acute practice with blood withdrawal and reinfusion within a few days, Hbmass seems to be the only option for revealing this practice. © 2009 John Wiley & Sons A/S.

Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects.

PubMed

Guzmán-Uribe, Daniela; Alvarado-Estrada, Keila Neri; Pierdant-Pérez, Mauricio; Torres-Álvarez, Bertha; Sánchez-Aguilar, Jesus Martin; Rosales-Ibáñez, Raúl

2017-01-01

The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group). Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues.

THE MECHANISM OF THE INFLAMMATORY PROCESS : III. ELECTROPHORETIC MIGRATION OF INERT PARTICLES AND BLOOD CELLS IN GELATIN SOLS AND GELS WITH REFERENCE TO LEUCOCYTE EMIGRATION THROUGH THE CAPILLARY WALL.

PubMed

Abramson, H A

1928-07-20

1. Quartz particles and certain other particles move cataphoretically in certain soft gelatin gels, with the same velocity as in the sol. The speed is a function of the true viscosity of the sol or gel, and it is See PDF for Structure apparently not altered in these soft gels by the presence of gel structure. It is proportional to the applied difference of potential. 2. This finding is compatible with the fact that certain sols undergo gelation with no increase of the true viscosity although a marked change in the apparent viscosity takes place. 3. Red cells in soft gelatin-serum gels show a distinct difference in behavior. They migrate through the sol or gel with a speed that is about twice as great as the leucocytes and quartz particles, which latter particles migrate with the same velocity. This ratio has been found to hold for serum and plasma. The absolute velocities are comparatively slightly decreased by the presence of the gel. 4. In more concentrated or stiffer gels, leucocytes, red cells and quartz particles all move at first with the same velocity. By producing mechanical softening of these gels (shearing from cataphoretic movement of the micells within the cell) the red cells presently resume their previous property of independent migration through the gel. 5. The movements of particles in gelatin gels produced by a magnetic force or the force of gravity are of a different nature than those movements produced by cataphoresis. 6. The mechanical nature of obstruction to the cataphoretic migration of leucocytes and red cells in fibrin gels is briefly described. 7. The correlation of cataphoresis of microscopic particles in gels with the order of magnitude and nature of the potential differences in the capillary wall, lends additional evidence to the theory that polymorphonuclear leucocyte emigration and migration are dependent upon these potential differences.

Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects

PubMed Central

GUZMÁN-URIBE, Daniela; ALVARADO-ESTRADA, Keila Neri; PIERDANT-PÉREZ, Mauricio; TORRES-ÁLVAREZ, Bertha; SÁNCHEZ-AGUILAR, Jesus Martin; ROSALES-IBÁÑEZ, Raúl

2017-01-01

Abstract Oral mucosa has been highlighted as a suitable source of epidermal cells due to its intrinsic characteristics such as its higher proliferation rate and its obtainability. Diabetic ulcers have a worldwide prevalence that is variable (1%-11%), meanwhile treatment of this has been proven ineffective. Tissue-engineered skin plays an important role in wound care focusing on strategies such autologous dermal-epidermal substitutes. Objective The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Material and Methods Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group). Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. Results It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Conclusion Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues. PMID:28403359

The Effect of Intra-articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis

PubMed Central

Borić, Igor; Rod, Eduard; Jeleč, Željko; Radić, Andrej; Vrdoljak, Trpimir; Skelin, Andrea; Trbojević-Akmačić, Irena; Plečko, Mihovil; Primorac, Dragan

2017-01-01

Osteoarthritis (OA) is one of the leading musculoskeletal disorders in the adult population. It is associated with cartilage damage triggered by the deterioration of the extracellular matrix tissue. The present study explores the effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non-randomized, interventional, single-center, open-label clinical trial was conducted from January 2016 to April 2017. A total of 17 patients were enrolled in the study, and 32 knees with osteoarthritis were assessed. Surgical intervention (lipoaspiration) followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s) was performed in all patients. Patients were assessed for visual analogue scale (VAS), delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and immunoglobulin G (IgG) glycans at the baseline, three, six and 12 months after the treatment. Magnetic resonance sequence in dGEMRIC due to infiltration of the anionic, negatively charged contrast gadopentetate dimeglumine (Gd-DTPA2−) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. In addition, dGEMRIC consequently reflected subsequent changes in the mechanical axis of the lower extremities. The results of our study indicate that the use of autologous and microfragmented adipose tissue in patients with knee OA (measured by dGEMRIC MRI) increased glycosaminoglycan (GAG) content in hyaline cartilage, which is in line with observed VAS and clinical results. PMID:29027984

Autologous platelet-rich plasma in the treatment of venous leg ulcers in primary care: a randomised controlled, pilot study.

PubMed

Burgos-Alonso, Natalia; Lobato, Igone; Hernández, Igone; Sebastian, Kepa San; Rodríguez, Begoña; March, Anna Giné; Perez-Salvador, Adriana; Arce, Veronica; Garcia-Alvarez, Arturo; Gomez-Fernandez, Maria Cruz; Grandes, Gonzalo; Andia, Isabel

2018-06-01

To examine the potential efficacy and safety of autologous platelet-rich plasma (PRP) in comparison with the conventional treatment (standard care, SoC) for the treatment of leg ulcers in patients with chronic venous insufficiency, in a primary health-care setting. A Phase I-II, open-label, parallel-group, multicentre, randomised pilot study was conducted. The outcome variables at baseline and at weeks five and nine included reduction in the ulcer area, Chronic Venous Insufficiency Quality of Life Questionnaire score, cost of the treatment for up to nine weeks and average weekly cure rate. A total of eight patients, each with at least a six-month history of venous leg ulcer (VLUs), were included in the study. A total of 12 ulcers were treated with either autologous PRP or standard SoC. Patients treated with PRP required wound care only once per week. In the SoC group, patients required intervention 2-3 times per week. A reduction in the mean ulcer size in the PRP group was 3.9cm 2 compared with the SoC group at 3.2cm 2 , although the sample size was insufficient to reach statistical significance. Improvement in quality of life (QoL) score was observed in the patients in the PRP group. This study offers proof-of-concept of the feasibility and safety of PRP treatment to inform larger clinical trials in patients with VLUs. Our preliminary results suggest that PRP delivers a safe and effective treatment for VLU care that can be implemented in primary health-care settings.

Advantages of autologous blood transfusion in off-pump coronary artery bypass.

PubMed

Ela, Yuksel; Emmiler, Mustafa; Kocogullari, Cevdet Ugur; Terzi, Yuksel; Sivaci, Remziye Gul; Cekirdekci, Ahmet

2009-10-01

In this randomized controlled study, we investigated the effects of autologous Hemobag blood transfusion (AHBT) and allogenic blood transfusion (ABT) in off-pump coronary artery bypass (OPCAB) surgery. Sixty patients who underwent surgery between February 2008 and August 2008 were randomized into 2 groups. The AHBT group (n = 30) consisted of patients who received autologous Hemobag blood transfusion, and the ABT group (n = 30) consisted of patients who received allogenic blood transfusion. All patients underwent OPCAB via sternotomy. The time to extubation, chest tube drainage volume, postoperative white blood cell counts, amount of blood transfusion, sedimentation rate, C-reactive protein concentration, postoperative temperature, and the presence of atelectasis were recorded in the intensive care unit. Intraoperative bleeding and fluid resuscitation were similar in the 2 groups (P > .05); however, there were significant decreases in postoperative blood loss, extubation period, postoperative white cell counts, sedimentation rate, incidence of atelectasis, C-reactive protein, and fever in the AHBT group compared with the ABT group (P < .05). The rate of atrial fibrillation in the AHBT group tended to be lower than in the ABT group. Autologous blood transfusion in OPCAB may be beneficial in certain cardiac surgery patients; however, these beneficial effects require further study to be proved.

Cell culture in autologous fibrin scaffolds for applications in tissue engineering.

PubMed

de la Puente, Pilar; Ludeña, Dolores

2014-03-10

In tissue engineering techniques, three-dimensional scaffolds are needed to adjust and guide cell growth and to allow tissue regeneration. The scaffold must be biocompatible, biodegradable and must benefit the interactions between cells and biomaterial. Some natural biomaterials such as fibrin provide a structure similar to the native extracellular matrix containing the cells. Fibrin was first used as a sealant based on pools of commercial fibrinogen. However, the high risk of viral transmission of these pools led to the development of techniques of viral inactivation and elimination and the use of autologous fibrins. In recent decades, fibrin has been used as a release system and three-dimensional scaffold for cell culture. Fibrin scaffolds have been widely used for the culture of different types of cells, and have found several applications in tissue engineering. The structure and development of scaffolds is a key point for cell culture because scaffolds of autologous fibrin offer an important alternative due to their low fibrinogen concentrations, which are more suitable for cell growth. With this review our aim is to follow methods of development, analyze the commercial and autologous fibrins available and assess the possible applications of cell culture in tissue engineering in these three-dimensional structures. Copyright © 2013 Elsevier Inc. All rights reserved.

Autologous fat transplantation for the treatment of linear scleroderma en coup de sabre.

PubMed

Ibler, Kristina S; Gramkow, Christina; Siemssen, Peter A

2015-01-01

Scleroderma en coup de sabre is a disfiguring disease for which only limited therapeutic options exist. Three cases of facial linear scleroderma treated with autologous fat transplantation with acceptable results are presented. Autologous fat transplantation was preferred to corrective surgery because of the extent of the lesions and absence of any associated facial distortion. Fat as a filler was chosen to reduce the risk of adverse effects. Adipocytes are suggested to have wider biological effects than other fillers and may offer more durable results. At least two transplantations were needed to evoke a significant effect.

Autologous Bone Plug Supplemented With Autologous Chondrocyte Implantation in Osteochondral Defects of the Knee.

PubMed

Bhattacharjee, Atanu; McCarthy, Helen S; Tins, Bernhard; Roberts, Sally; Kuiper, J H; Harrison, Paul E; Richardson, James B

2016-05-01

Structural and functional outcome of bone graft with first- or second-generation autologous chondrocyte implantation (ACI) in treating cartilage and subchondral bone defect has not been reported previously. To evaluate the outcome of simultaneous transplantation of an autologous bone plug with first- or second-generation ACI for restoration of concomitant subchondral bone and full-thickness cartilage defect in the femoral condyle of the knee. Case series; Level of evidence, 4. Seventeen patients (mean ± SD age, 27 ± 7 years; range, 17-40 years)-12 with osteochondritis dissecans (International Cartilage Repair Society [ICRS] grades 3 and 4) and 5 with an isolated osteochondral defect (ICRS grade 4)-had the defect reconstructed with implantation of a unicortical autologous bone graft combined with ACI (the OsPlug technique). Functional outcome was assessed with Lysholm scores obtained preoperatively and at 1 and 5 years postoperatively. The repair site was evaluated with the Oswestry Arthroscopy Score (OAS), MOCART score (magnetic resonance observation of cartilage repair tissue), and ICRS II histology score. Formation of a subchondral lamina and lateral integration of the bone grafts were evaluated from magnetic resonance imaging scans. The mean defect size was 4.5 ± 2.6 cm(2) (range, 1-9 cm(2)), and the mean depth was 11.3 ± 5 mm (range, 5-18 mm). The preoperative Lysholm score improved from 45 (interquartile range [IQR], 24; range, 16-79) to 77 (IQR, 28; range, 41-100) at 1 year (P = .001) and 70 (IQR, 35; range, 33-91) at 5 years (P = .009). The mean OAS of the repair site was 6.2 (range, 0-9) at a mean of 1.3 years. The mean MOCART score was 61 ± 22 (range, 20-85) at 2.6 ± 1.8 years. Histology demonstrated generally good integration of the repair cartilage with the underlying bone. Poor lateral integration of the bone graft, as assessed on magnetic resonance imaging scan, and a low OAS were significantly associated with a poor Lysholm score and failure. A

Impact of Postoperative Antibiotic Prophylaxis Duration on Surgical Site Infections in Autologous Breast Reconstruction.

PubMed

Drury, Kerry E; Lanier, Steven T; Khavanin, Nima; Hume, Keith M; Gutowski, Karol A; Thornton, Brian P; Hansen, Nora M; Murphy, Robert X; Fine, Neil A; Kim, John Y S

2016-02-01

Although some surgeons prescribe prolonged postoperative antibiotics after autologous breast reconstruction, evidence is lacking to support this practice. We used the Tracking Operations and Outcomes for Plastic Surgeons database to evaluate the association between postoperative antibiotic duration and the rate of surgical site infection (SSI) in autologous breast reconstruction. The intervention of interest for this study was postoperative duration of antibiotic prophylaxis: either discontinued 24 hours after surgery or continued beyond 24 hours. The primary outcome variable of interest for this study was the presence of SSI within 30 days of autologous breast reconstruction. Cohort characteristics and 30-day outcomes were compared using χ² and Fischer exact tests for categorical variables and Student t tests for continuous variables. Multivariate logistic regression was used to control for confounders. A total of 1036 patients met inclusion criteria for our study. Six hundred fifty-nine patients (63.6%) received antibiotics for 24 hours postoperatively, and 377 patients (36.4%) received antibiotics for greater than 24 hours. The rate of SSI did not differ significantly between patients given antibiotics for only 24 hours and those continued on antibiotics beyond the 24-hour postoperative time period (5.01% vs 2.92%, P = 0.109). Furthermore, antibiotic duration was not predictive of SSI in multivariate regression modeling. We did not find a statistically significant difference in the rate of SSI in patients who received 24 hours of postoperative antibiotics compared to those that received antibiotics for greater than 24 hours. These findings held for both purely autologous reconstruction as well as latissimus dorsi reconstruction in conjunction with an implant. Thus, our study does not support continuation of postoperative antibiotics beyond 24 hours after autologous breast reconstruction.

A Review of Autologous Stem Cell Transplantation in Lymphoma.

PubMed

Zahid, Umar; Akbar, Faisal; Amaraneni, Akshay; Husnain, Muhammad; Chan, Onyee; Riaz, Irbaz Bin; McBride, Ali; Iftikhar, Ahmad; Anwer, Faiz

2017-06-01

Chemotherapy remains the first-line therapy for aggressive lymphomas. However, 20-30% of patients with non-Hodgkin lymphoma (NHL) and 15% with Hodgkin lymphoma (HL) recur after initial therapy. We want to explore the role of high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) for these patients. There is some utility of upfront consolidation for-high risk/high-grade B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma, but there is no role of similar intervention for HL. New conditioning regimens are being investigated which have demonstrated an improved safety profile without compromising the myeloablative efficiency for relapsed or refractory HL. Salvage chemotherapy followed by HDT and rescue autologous stem cell transplant remains the standard of care for relapsed/refractory lymphoma. The role of novel agents to improve disease-related parameters remains to be elucidated in frontline induction, disease salvage, and high-dose consolidation or in the maintenance setting.

Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

DTIC Science & Technology

2017-07-01

AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve...of Decellularized Nerve Allograft with 5a. CONTRACT NUMBER Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve 5b. GRANT NUMBER W81XWH...commercially available decellularized processed peripheral nerve allograft scaffold (Avance® Nerve Graft, AxoGen, Alachua FL) with autologous bone marrow

Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury

PubMed Central

Masuzawa, Akihiro; Black, Kendra M.; Pacak, Christina A.; Ericsson, Maria; Barnett, Reanne J.; Drumm, Ciara; Seth, Pankaj; Bloch, Donald B.; Levitsky, Sidney; Cowan, Douglas B.

2013-01-01

Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 ± 1.7 × 106/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased (P < 0.05) creatine kinase MB, cardiac troponin-I, and apoptosis significantly in the RI zone. Infarct size following 4 wk of recovery was decreased significantly in RI-mitochondria (7.9 ± 2.9%) compared with RI-vehicle (34.2 ± 3.3%, P < 0.05). Serial echocardiograms showed that RI-mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2–8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury. PMID:23355340

Evaluation of ex vivo produced endothelial progenitor cells for autologous transplantation in primates.

PubMed

Qin, Meng; Guan, Xin; Zhang, Yu; Shen, Bin; Liu, Fang; Zhang, Qingyu; Ma, Yupo; Jiang, Yongping

2018-01-22

Autologous transplantation of endothelial progenitor cells (EPCs) is a promising therapeutic approach in the treatment of various vascular diseases. We previously reported a two-step culture system for scalable generation of human EPCs derived from cord blood CD34 + cells ex vivo. Here, we now apply this culture system to expand and differentiate human and nonhuman primate EPCs from mobilized peripheral blood (PB) CD34 + cells for the therapeutic potential of autologous transplantation. The human and nonhuman primate EPCs from mobilized PB CD34 + cells were cultured according to our previously reported system. The generated adherent cells were then characterized by the morphology, surface markers, nitric oxide (NO)/endothelial NO synthase (eNOS) levels and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake/fluorescein isothiocyanate (FITC)-lectin binding actives. Furthermore, the efficacy and safety studies were performed by autologous transplantation via hepatic portal vein injection in a nonhuman primate model with acute liver sinusoidal endothelial cell injury. The mobilized PB CD34 + cells from both human and nonhuman primate were efficiently expanded and differentiated. Over 2 × 10 8 adherent cells were generated from 20 mL mobilized primate PB (1.51 × 10 6  ± 3.39 × 10 5 CD34 + cells) by 36-day culture and more than 80% of the produced cells were identified as EPCs/endothelial cells (ECs). In the autologous transplant model, the injected EPC/ECs from nonhuman primate PB were scattered in the intercellular spaces of hepatocytes at the hepatic tissues 14 days post-transplantation, indicating successful migration and reconstitution in the liver structure as the functional EPCs/ECs. We successfully applied our previous two-step culture system for the generation of primate EPCs from mobilized PB CD34 + cells, evaluated the phenotypes ex vivo, and transplanted autologous EPCs/ECs in a nonhuman primate model. Our study indicates that

A novel autologous scaffold for diced-cartilage grafts in dorsal augmentation rhinoplasty.

PubMed

Bullocks, Jamal M; Echo, Anthony; Guerra, Gerardo; Stal, Samuel; Yuksel, Eser

2011-08-01

Diced-cartilage grafts have been used for dorsal nasal augmentation for several years with good results. However, compounds such as Surgicel and temporalis fascia used as a wrap have inherent problems associated with them, predominantly inflammation and graft resorption. An autologous carrier could provide stabilization of cartilage grafts while avoiding the complications seen with earlier techniques. In our patients, a malleable construct was used for dorsal nasal augmentation in which autologous diced-cartilage grafts were stabilized with autologous tissue glue (ATG) created from platelet-rich plasma (platelet gel) and platelet-poor plasma (fibrin glue). A prospective analysis of 68 patients, who underwent dorsal nasal augmentation utilizing ATG and diced-cartilage grafts between 2005 and 2008, were included in the study. Although there was notable maintenance of the dorsal height, no complications occurred that required explantation over a mean follow-up of 15 months. The use of ATG to stabilize diced-cartilage grafts is a safe, reliable technique for dorsal nasal augmentation. The platelet gel provides growth factors while the fibrin glue creates a scaffold that allows stabilization and diffusion of nutrients to the cartilage graft.

Evolution of Autologous Chondrocyte Repair and Comparison to Other Cartilage Repair Techniques

PubMed Central

Dewan, Ashvin K.; Gibson, Matthew A.; Elisseeff, Jennifer H.; Trice, Michael E.

2014-01-01

Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques. Methods. We searched PubMed from 1949 to 2014 for the keywords “autologous chondrocyte implantation” (ACI) and “cartilage repair” in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks. Results. Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells) and associated scaffolds (natural or synthetic, hydrogels or membranes). ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient's knee as evaluated by multiple clinical indices and the quality of regenerated tissue. Conclusion. Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients. PMID:25210707

Hyaline cartilage degenerates after autologous osteochondral transplantation.

PubMed

Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

2004-11-01

Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

PubMed

Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki

2015-08-01

The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Autologous blood donation in a small general acute-care hospital.

PubMed Central

Mott, L. S.; Jones, M. J.

1995-01-01

Increased public concerns about infectious risk associated with homologous blood transfusions have led to a significant increase in autologous blood collections. In response, blood banks and large hospitals have implemented autologous blood donation programs (ABDPs). Small hospitals lack the technical resources and patient case loads to effectively institute ABDPs. A preoperative ABDP designed to increase availability and patient convenience--and, therefore, utilization--is described. The program created in a rural 90-bed general acute-care hospital processed 105 donors and collected 197 units over a 38-month period. The percentage of the collected units that were transfused was 44.7%, and only 6.1% of participating patients required homologous transfusions. Comparisons of hematological and clinical data with previously published results indicate that small-scale preoperative ABDPs are clinically effective, safe, and provide cost-efficient utilization of the safest blood supply available. PMID:7674344

Comparison between sensitivity of autologous skin serum test and autologous plasma skin test in patients with Chronic Idiopathic Urticaria for detection of antibody against IgE or IgE receptor (FcεRIα).

PubMed

Sajedi, Vahid; Movahedi, Masoud; Aghamohammadi, Asghar; Aghamohamadi, Asghar; Gharagozlou, Mohammad; Ghareguzlou, Mohammad; Shafiei, Alireza; Soheili, Habib; Sanajian, Nahal

2011-06-01

Intradermal injection of autologous serum and plasma elicit a cutaneous reactivity in almost 45-60% of patients with Chronic Idiopathic Urticaria (CIU). This reactivity is associated with the presence of auto antibodies against IgE or IgE receptors. This study was carried out to compare the cutaneous reactivity of autologous serum and plasma skin tests in a series of patients with CIU for diagnosis of auto antibodies against IgE or IgE receptor. Fifty eight patients with CIU were injected intradermally with autologous serum and plasma (anticoagulated by citrate). Histamine was used as positive control and normal saline as negative control. The study group was checked by routine laboratory tests (CBC, U/A etc), allergens with skin prick tests, and serum IgE level, and auto antibodies against thyroid as well. Duration of urticaria was another factor which was assessed.There was no significant difference between positive ASST and positive APST patients for the above mentioned tests. 77.6% of the patients were Positive for APST and 65.5% were ASST positive. Duration of urticaria was longer in patients with positive ASST and APST than ASST and APST negative patients, although the difference was not statistically significant.Autologus serum skin test (ASST) and autologous plasma skin test (APST) could be used for estimation of duration and severity of urticaria and planning for the treatment.

Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

PubMed Central

Akita, Sadanori; Akino, Kozo; Hirano, Akiyoshi; Ohtsuru, Akira; Yamashita, Shunichi

2010-01-01

Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years. PMID:21151652

The effect of autologous fibrin tissue adhesive on postoperative cerebrospinal fluid leak in spinal cord surgery: a randomized controlled trial.

PubMed

Nakamura, Hiroshi; Matsuyama, Yukihiro; Yoshihara, Hisatake; Sakai, Yoshihito; Katayama, Yoshito; Nakashima, Shojiro; Takamatsu, Jyunki; Ishiguro, Naoki

2005-07-01

A prospective randomized study evaluating the efficacy of autologous fibrin tissue adhesive for decreasing postoperative cerebrospinal fluid (CSF) leak in spinal cord surgery. To compare postoperative CSF leak in 3 groups (i.e., autologous fibrin tissue adhesive used, commercial fibrin glue used, and no fibrin tissue adhesive used) of patients undergoing spinal surgery who needed dural incision. Spinal cord operations, particularly when dural incision is inevitable, sometimes involve postoperative CSF leak. Because CSF leak is a serious complication, countermeasure is necessary to prevent it after dural suture. Commercial fibrin tissue adhesive was formerly used. Because the possibility of prion infection was widely noticed, commercial fibrin tissue adhesive containing animal components has been used less often. In 13 of 39 cases in which dural incision would be made, 400 mL whole blood was drawn, and autologous fibrin tissue adhesive was made of plasma. Cases were divided into 3 groups: (1) dural closure alone, (2) use of autologous fibrin tissue adhesive after dural closure, and (3) use of commercial fibrin tissue adhesive after dural closure. The primary outcome measure was determined as postoperative (3 days) volume of drainage fluid, and results were analyzed using the analysis of variance. The secondary outcome measure was general blood test, coagulation assay, and plasma fibrinogen, and these were analyzed also using the analysis of variance. There was a significant difference in the primary outcome between the autologous and control groups. No complications such as infection or continuous CSF leak were observed in any case. The mean volume of drainage fluid was 586.2 mL in the group with autologous fibrin tissue adhesive and 1026.1 mL in the group without fibrin tissue adhesive. The volume of drainage fluid was significantly lower in the former group than that in the latter group. There was no statistical difference between the volumes of the group with

In vivo traffic of indium-111-oxine labeled human lymphocytes collected by automated apheresis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Read, E.J.; Keenan, A.M.; Carter, C.S.

1990-06-01

The in vivo traffic patterns of autologous lymphocytes were studied in five normal human volunteers using lymphocytes obtained by automated apheresis, separated on Ficoll-Hypaque gradients, and labeled ex vivo with {sup 111}In-oxine. Final lymphocyte infusions contained 1.8-3.1 X 10(9) cells and 270-390 microCi (9.99-14.43 MBq) {sup 111}In, or 11-17 microCi (0.41-0.63 MBq) per 10(8) lymphocytes. Gamma imaging showed transient lung uptake and significant retention of radioactivity in the liver and spleen. Progressive uptake of activity in normal, nonpalpable axillary and inguinal lymph nodes was seen from 24 to 96 hr. Accumulation of radioactivity also was demonstrated at the forearm skinmore » test site, as well as in its associated epitrochlear and axillary lymph nodes, in a subject who had been tested for delayed hypersensitivity with tetanus toxoid. Indium-111-oxine labeled human lymphocytes may provide a useful tool for future studies of normal and abnormal lymphocyte traffic.« less

In vitro immunization of patient T cells with autologous bone marrow antigen presenting cells pulsed with tumor lysates.

PubMed

Coulon, V; Ravaud, A; Gaston, R; Delaunay, M; Pariente, J L; Verdier, D; Scrivante, V; Gualde, N

2000-12-01

Presentation of cell-associated antigen to T cells is a critical event in the initiation of an anti-tumor immune response but it appears to often be deficient or limiting. Here we report an experimental system for stimulation of human T lymphocytes using autologous antigen presenting cells (APCs) and autologous tumor cells. Two types of APCs were prepared from human bone marrow: MC and DC. MC were produced by using GM-CSF and SCF. DC were obtained with the same cytokines plus IL-4. DC and MC were generated in parallel from the same patients and their phenotypes and capacities to prime T lymphocytes were analyzed and compared. MC were CD14+, CD1a-, CD33+ and HLA-DR+. Two populations of DC were defined: immature DC were uniformly CD1a-; mature DC expressed CD1a, CD80, CD86, HLA-DR, CD54 and CD58 but lacked surface CD14. Stimulation of autologous T lymphocytes was studied by measuring their proliferation and cytotoxic function. In more than 80% of our experiments the proliferation of autologous T lymphocytes cocultured with APC pulsed or not with tumor cell lysates was higher than that of T cells cultured alone. DC were more effective than MC in stimulating proliferation of lymphocytes. The capacity of a patient's autologous bone marrow-derived APC to stimulate T cells when exposed to autologous tumor cell lysates suggest that such antigen-exposed APC may be useful in specific anti-tumor immunotherapy protocols. Copyright 2000 Wiley-Liss, Inc.

Sterigmatomyces halophilus β-glucan improves the immune response and bacterial resistance in Pacific red snapper (Lutjanus peru) peripheral blood leucocytes: In vitro study.

PubMed

Reyes-Becerril, Martha; Guardiola, Francisco A; Sanchez, Veronica; Maldonado, Minerva; Angulo, Carlos

2018-04-21

β-Glucans are naturally occurring polysaccharides that are produced by bacteria, fungi and yeast. They are considered immunostimulants in fish acting on non-specific defense mechanism. Yeast-derived glucans from cell wall (Sterigmatomyces halophilus, β-Gluc/Sh) have been used for this purpose in this study. Therefore, an in vitro assay using peripheral blood leucocytes (PBLs) from Pacific red snapper was performed to evaluate the stimulant effects of β-Gluc/Sh and zymosan A (positive control) for 12 and 24 h and after bacterial challenge with Aeromonas hydrophila at 24 h. In addition, structural characterization of this marine yeast glucan was performed by proton nuclear magnetic resonance (NMR) revealing structures containing (1-6)-branched (1-3)-β-D-glucan. PBLs responded positively to β-Gluc/Sh where cell viability was higher than 80%. After challenge, β-Gluc/Sh was able to inhibit cytotoxicity caused by A. hydrophila, highlighting that the PBLs incubated with β-Gluc/Sh significantly increased the non-specific immune response, such as phagocytic activity, respiratory burst, nitric oxide and peroxidase activities followed by an increase in superoxide dismutase and catalase activities after 12 and 24 h post-stimulation and after challenge with the pathogen. Regarding induction of antioxidant gene expression, it was more pronounced in stimulated β-Gluc/Sh leucocytes compared to other groups at all experimental times of the trial and after bacterial challenge. Indeed, our results clearly showed the ability of leucocytes to strongly react to β-Gluc/Sh with an increase in cytokine gene expression, particularly the IL-1β, IL-10 and IL-17 genes. These results confirm that S. halophilus yeast-derived β-glucan, isolated from an extreme marine environment, is beneficial for increasing innate immune response and enhancing resistance against A. hydrophila in vitro. Copyright © 2018. Published by Elsevier Ltd.

Human T-Cell Clones from Autoimmune Thyroid Glands: Specific Recognition of Autologous Thyroid Cells

NASA Astrophysics Data System (ADS)

Londei, Marco; Bottazzo, G. Franco; Feldmann, Marc

1985-04-01

The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatability antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves' disease were cloned in mitogen-free interleukin-2 (T-cell growth factor). The clones were expanded and their specificity was tested. Three types of clones were found. One group, of T4 phenotype, specifically recognized autologous thyroid cells. Another, also of T4 phenotype, recognized autologous thyroid or blood cells and thus responded positively in the autologous mixed lymphocyte reaction. Other clones derived from cells that were activated in vivo were of no known specificity. These clones provide a model of a human autoimmune disease and their analysis should clarify mechanisms of pathogenesis and provide clues to abrogating these undesirable immune responses.

Augmentation of autologous hamstring graft during anterior cruciate ligament reconstruction using the bone chip technique.

PubMed

Nha, Kyung Wook; Shetty, Gautam M; Ahn, Jin Hwan; Lee, Yong Seuk; Chae, Dong Ju; Nam, Hyok Woo; Lee, Dae Hee

2010-01-01

The use of autologous quadrupled hamstring tendon graft is a well-known technique for anterior cruciate ligament reconstruction. In cases where the diameter of the graft is inadequate, the stability of graft fixation and subsequent bone to tendon healing may be compromised. We describe a new technique to augment the autologous double looped hamstring tendon graft during anterior cruciate ligament reconstruction using cancellous bone chips. This simple technique effectively enhances graft fixation and stability.

Augmentation of the Nasal Dorsum Using the Multistrip Autologous Cartilage Technique.

PubMed

Liu, Liqiang; Bu, Zhaoyun; Fan, Jincai; Tian, Jia; Gan, Cheng; Yang, Zengjie; Jiao, Hu

2017-12-01

Nasal augmentation is a popular modern technique requested by many Asian people. There are two kinds of autologous cartilage used to augment the nose at present: carved as a monobloc or diced into pieces. Each approach has its pros and cons. The authors performed their surgical technique on a group of 28 patients. Twenty of these patients had undergone rhinoplasties performed before referral to our hospital; eight of these patients had undergone a primary rhinoplasty. Bilateral conchal, nasal septum, or rib cartilage was harvested; deep temporal fascia or abdominal muscle fascia to be prepared for packing stripped cartilage was also removed at this time. The cartilage was placed on a plastic cutting board and cut into strips with a transverse section of 1 × 1 mm. Then, these strips were packed and covered by fascia to form the grafts. The median follow-up was 23 months (range, 12 to 48 months). Twenty-two patients were satisfied with their augmented noses. Through examinations, biopsies, and magnetic resonance imaging scans, less resorption was observed with the multistrip autologous cartilage technique. Junctional stepoffs, excessive prominence, and slanting grafts occurred in three patients, two of whom had revisions. Using multistrip autologous cartilage grafts is an easier method to perform and could be another alternative technique for augmentative and reconstructive rhinoplasties.

Hemoglobin mass and biological passport for the detection of autologous blood doping.

PubMed

Pottgiesser, Torben; Echteler, Tobias; Sottas, Pierre-Edouard; Umhau, Markus; Schumacher, Yorck Olaf

2012-05-01

The most promising attempt to reveal otherwise undetectable autologous blood doping is the Athlete Biological Passport enabling a longitudinal monitoring of hematological measures. Recently, the determination of hemoglobin mass (tHb) was suggested to be incorporated in the adaptive model of the Athlete Biological Passport. The purpose therefore was to evaluate the performance of tHb as part of the adaptive model for the detection of autologous blood transfusions in a longitudinal blinded study. Twenty-one subjects were divided into a doped group (n = 11) and a control group (n = 10). During the time course of a simulated cycling season (42 wk) including three major competitions (Classics, Grand Tour, World Championships), multiple autologous transfusions of erythrocyte concentrates were assigned in the doped group. A blinded investigator ordered up to 10 tHb measurements (carbon monoxide rebreathing) per subject, mimicking an intelligent doping testing approach in obtaining hematological data (tHb, OFFmass (novel marker including reticulocytes), and respective sequences) for the adaptive model. The final analysis included 199 of 206 overall tHb measurements. The use of tHb, OFFmass, and their sequences as markers of the adaptive model at the 99% specificity level allowed identification of 10 of 11 doped subjects (91% sensitivity) including one false positive in the control group. At the 99.9% specificity level, 8 of 11 subjects were identified without false positives (73% sensitivity). It seems that the problems of tHb determination by carbon monoxide rebreathing limit the application of this method in antidoping. Because of its potential to detect individual abnormalities associated with autologous blood transfusions shown in this study, a method for tHb determination that is compatible with today's standards of testing should be the focus of future research.

Immediate breast reconstruction using autologous skin graft associated with breast implant.

PubMed

Dutra, A K; Andrade, W P; Carvalho, S M T; Makdissi, F B A; Yoshimatsu, E K; Domingues, M C; Maciel, M S

2012-02-01

Immediate breast reconstruction with skin graft is still little mentioned in the literature. Follow-up studies regarding the technique aspects are particularly scarce. The objective was to detail immediate breast reconstruction using autologous skin graft. Patients (n = 49) who underwent mastectomies and autologous immediate breast reconstruction with skin graft associated with a breast implant at A. C. Camargo Hospital (São Paulo, Brazil) between January 2007 and July 2010 were included. Information on clinical data, technique details and clinical outcome were prospectively collected. Following mastectomy, the autologous full-thickness skin graft was obtained through an inframammary fold incision along the contralateral breast in most patients. The skin graft was placed on the surface of the pectoralis major muscle after adjustments to conform to the mastectomy defect. A minimum of 10-month follow-up period was established. Patients' age ranged from 35 to 55 years and all received a silicone gel textured surface implant to obtain the necessary breast mound. The mean surgical time was 45 min, and the mean amount of skin resection was 4.5 cm in the largest diameter. Follow-up ranged from 10 to 35 months (median 23). All patients had silicone-gel textured surface implants to perform the breast mound reconstruction. No complications were observed in 87.8% of reconstructions. Forty-six patients (94%) had no complaints about the donor-site aesthetics. The result was a breast mound with a central ellipse of healed skin graft. Three (6%) poor results were observed. Thirty-six patients (67%) reported the results as good or very good. Our results lead us to conclude that autologous skin graft provided a reliable option in immediate breast reconstruction to skin-sparing mastectomy defects. The technique accomplished a single-stage implant breast reconstruction when there is inadequate skin coverage. Copyright © 2011 British Association of Plastic, Reconstructive and

Breast Augmentation by Water-Jet Assisted Autologous Fat Grafting: A Report of 300 Operations.

PubMed

Muench, Daniel P

2016-04-01

Background  The BEAULI -method (Breast Augmentation by Lipotransfer) is available for extraction and processing of large transplantable fat quantities. The aim of this work is to describe the surgical technique precisely and reproducibly and to provide an overview of the autologous fat transfer based on surgical experience. Method  The author performed 300 autologous fat transplantations on 254 women between September 3, 2010, and May 13, 2015. Patients desiring moderate volume increase, fuller and firmer breasts, as well as an optimization of the silhouette, ideally with the concurrent desire of the correction of unwanted fat deposits, were selected. The fat was extracted via water-jet assisted liposuction (Body-jet, Human Med AG, Schwerin, Germany), and the fat cells were subsequently separated with the Lipocollector ® (Human Med AG, Schwerin, Germany). Results  The results were assessed with a control exam and photo comparison and were based on the responses on a questionnaire. Overall, 35.9% of the patients defined the result as very good, 38.6% as good, 22.4% as satisfactory, and 3.1% as poor. Conclusion  This study shows that the autologous fat cell transplantation into the female breast via water-jet assisted liposuction achieves a moderate and harmoniously appearing breast volume enlargement as well as contour improvement. Further studies with more cases and longer observation periods over several years could contribute to improving the method of the autologous fat transfer regarding the grow-in rate, efficiency, and safety.

Treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation: a systematic review.

PubMed

Oussedik, Sam; Tsitskaris, Konstantinos; Parker, David

2015-04-01

We performed a systematic review of the treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation to determine the differences in patient outcomes after these procedures. We searched PubMed/Medline, Embase, and The Cochrane Library databases in the period from January 10 through January 20, 2013, and included 34 articles in our qualitative analysis. All studies showed improvement in outcome scores in comparison with baseline values, regardless of the treatment modality. The heterogeneity of the results presented in the studies precluded a meta-analysis. Microfracture appears to be effective in smaller lesions and is usually associated with a greater proportion of fibrocartilage production, which may have an effect on durability and eventual failure. Autologous chondrocyte implantation is an effective treatment that may result in a greater proportion of hyaline-like tissue at the repair site, which may in turn have a beneficial effect on durability and failure; it appears to be effective in larger lesions. Autologous chondrocyte implantation with periosteum has been shown to be associated with symptomatic cartilage hypertrophy more frequently than autologous chondrocyte implantation with collagen membrane. Matrix-associated autologous chondrocyte implantation is technically less challenging than the other techniques available, and in lesions greater than 4 cm(2), it has been shown to be more effective than microfracture. Level IV, systematic review of Level I-IV studies. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Label-free haemogram using wavelength modulated Raman spectroscopy for identifying immune-cell subset

NASA Astrophysics Data System (ADS)

Ashok, Praveen C.; Praveen, Bavishna B.; Campbell, Elaine C.; Dholakia, Kishan; Powis, Simon J.

2014-03-01

Leucocytes in the blood of mammals form a powerful protective system against a wide range of dangerous pathogens. There are several types of immune cells that has specific role in the whole immune system. The number and type of immune cells alter in the disease state and identifying the type of immune cell provides information about a person's state of health. There are several immune cell subsets that are essentially morphologically identical and require external labeling to enable discrimination. Here we demonstrate the feasibility of using Wavelength Modulated Raman Spectroscopy (WMRS) with suitable machine learning algorithms as a label-free method to distinguish between different closely lying immune cell subset. Principal Component Analysis (PCA) was performed on WMRS data from single cells, obtained using confocal Raman microscopy for feature reduction, followed by Support Vector Machine (SVM) for binary discrimination of various cell subset, which yielded an accuracy >85%. The method was successful in discriminating between untouched and unfixed purified populations of CD4+CD3+ and CD8+CD3+ T lymphocyte subsets, and CD56+CD3- natural killer cells with a high degree of specificity. It was also proved sensitive enough to identify unique Raman signatures that allow clear discrimination between dendritic cell subsets, comprising CD303+CD45+ plasmacytoid and CD1c+CD141+ myeloid dendritic cells. The results of this study clearly show that WMRS is highly sensitive and can distinguish between cell types that are morphologically identical.

Unicameral bone cysts: a comparison of injection of steroid and grafting with autologous bone marrow.

PubMed

Cho, H S; Oh, J H; Kim, H-S; Kang, H G; Lee, S H

2007-02-01

Open surgery is rarely justified for the initial treatment of a unicameral bone cyst, but there is some debate concerning the relative effectiveness of closed methods. This study compared the results of steroid injection with those of autologous bone marrow grafting for the treatment of unicameral bone cysts. Between 1990 and 2001, 30 patients were treated by steroid injection and 28 by grafting with autologous bone marrow. The overall success rates were 86.7% and 92.0%, respectively (p>0.05). The success rate after the initial procedure was 23.3% in the steroid group and 52.0% in those receiving autologous bone marrow (p<0.05), and the respective cumulative success rates after second injections were 63.3% and 80.0% (p>0.05). The mean number of procedures required was 2.19 (1 to 5) and 1.57 (1 to 3) (p<0.05), the mean interval to healing was 12.5 months (4 to 32) and 14.3 months (7 to 36) (p>0.05), and the rate of recurrence after the initial procedure was 41.7% and 13.3% in the steroid and in the autologous bone marrow groups, respectively (p<0.05). Although the overall rates of success of both methods were similar, the steroid group had higher recurrence after a single procedure and required more injections to achieve healing.

Cost-effectiveness analysis of implants versus autologous perforator flaps using the BREAST-Q.

PubMed

Matros, Evan; Albornoz, Claudia R; Razdan, Shantanu N; Mehrara, Babak J; Macadam, Sheina A; Ro, Teresa; McCarthy, Colleen M; Disa, Joseph J; Cordeiro, Peter G; Pusic, Andrea L

2015-04-01

Reimbursement has been recognized as a physician barrier to autologous reconstruction. Autologous reconstructions are more expensive than prosthetic reconstructions, but provide greater health-related quality of life. The authors' hypothesis is that autologous tissue reconstructions are cost-effective compared with prosthetic techniques when considering health-related quality of life and patient satisfaction. A cost-effectiveness analysis from the payer perspective, including patient input, was performed for unilateral and bilateral reconstructions with deep inferior epigastric perforator (DIEP) flaps and implants. The effectiveness measure was derived using the BREAST-Q and interpreted as the cost for obtaining 1 year of perfect breast health-related quality-adjusted life-year. Costs were obtained from the 2010 Nationwide Inpatient Sample. The incremental cost-effectiveness ratio was generated. A sensitivity analysis for age and stage at diagnosis was performed. BREAST-Q scores from 309 patients with implants and 217 DIEP flap reconstructions were included. The additional cost for obtaining 1 year of perfect breast-related health for a unilateral DIEP flap compared with implant reconstruction was $11,941. For bilateral DIEP flaps compared with implant reconstructions, the cost for an additional breast health-related quality-adjusted life-year was $28,017. The sensitivity analysis demonstrated that the cost for an additional breast health-related quality-adjusted life-year for DIEP flaps compared with implants was less for younger patients and earlier stage breast cancer. DIEP flaps are cost-effective compared with implants, especially for unilateral reconstructions. Cost-effectiveness of autologous techniques is maximized in women with longer life expectancy. Patient-reported outcomes findings can be incorporated into cost-effectiveness analyses to demonstrate the relative value of reconstructive procedures.

In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forstrom, L.A.; Loken, M.K.; Cook, A.

1981-04-01

Indium-111-labeled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labeling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6more » mCi of In-111-leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients.« less

In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forstrom, L.A.; Loken, M.K.; Cook, A.

1981-04-01

Indium-111-labelled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labelling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6more » mCi of In-111 leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients.« less

Autologous Fat Transfer for Thumb Carpometacarpal Joint Osteoarthritis: A Prospective Study.

PubMed

Herold, Christian; Rennekampff, Hans-Oliver; Groddeck, Robert; Allert, Sixtus

2017-08-01

Most operations for carpometacarpal joint osteoarthritis of the thumb irreversibly alter or destroy the anatomy. There is a high demand for minimally invasive alternatives. The authors report the results of autologous fat transfer for treatment of thumb carpometacarpal joint osteoarthritis. In a prospective study, 50 patients with thumb carpometacarpal joint osteoarthritis were observed for 1 year after autologous fat transfer. Manual liposuction and centrifugation were performed. Pain rating according to visual analogue pain scale; objective force of pinch grip and fist closure; and Disabilities of the Arm, Shoulder, and Hand questionnaire scores before and after treatment were analyzed. The average pain in stage 2 patients preoperatively was 7.7 ± 1.3; it was 1.8 ± 1.9 after 6 months and 2.4 ± 3.1 after 12 months. Patients with stage 2 osteoarthritis demonstrated a superior benefit from this treatment compared with patients with either stage 3 or stage 4 thumb carpometacarpal joint osteoarthritis. There were similar improvements for the parameters strength and Disabilities of the Arm, Shoulder, and Hand questionnaire score. No serious adverse events were observed. Autologous fat transplantation is an appealing alternative, especially in early-stage basal joint osteoarthritis of the thumb. The low invasiveness of the procedure and early recovery of patients compared with classical procedures such as trapeziectomy, and the superior long-term results compared with classical injection therapy, make this approach feasible as a first-line therapy in early-stage basal joint osteoarthritis of the thumb. Therapeutic, IV.

Differential patterns of endothelial and leucocyte activation in ‘typhus-like’ illnesses in Laos and Thailand

PubMed Central

Paris, D H; Jenjaroen, K; Blacksell, S D; Phetsouvanh, R; Wuthiekanun, V; Newton, P N; Day, N P J; Turner, G D H

2008-01-01

Scrub typhus is responsible for a large proportion of undifferentiated fevers in south-east Asia. The cellular tropism and pathophysiology of the causative agent, Orientia tsutsugamushi, remain poorly understood. We measured endothelial and leucocyte activation by soluble cell adhesion molecule enzyme-linked immunosorbent assays in 242 Lao and Thai patients with scrub or murine typhus, leptospirosis, dengue, typhoid and uncomplicated falciparum malaria on admission to hospital. Soluble E-selectin (sE-selectin) levels were lowest in dengue, sL-selectin highest in scrub typhus with a high sE-selectin to sL-selectin ratio in leptospirosis patients. In scrub typhus patients elevated sL-selectin levels correlated with the duration of skin rash (P = 0·03) and the presence of eschar (P = 0·03), elevated white blood cell (WBC) count (P = 0·007), elevated lymphocyte (P = 0·007) and neutrophil counts (P = 0·015) and elevated levels of sE-selectin correlated with the duration of illness before admission (P = 0·03), the presence of lymphadenopathy (P = 0·033) and eschar (P = 0·03), elevated WBC (P = 0·005) and neutrophil counts (P = 0·0003). In comparison, soluble selectin levels in murine typhus patients correlated only with elevated WBC counts (P = 0·03 for sE-selectin and sL-selectin). Soluble intercellular adhesion molecule-1 and soluble vascular adhesion molecule-1 levels were not associated significantly with any clinical parameters in scrub or murine typhus patients. The data presented suggest mononuclear cell activation in scrub typhus. As adhesion molecules direct leucocyte migration and induce inflammatory and immune responses, this may represent O. tsutsugamushi tropism during early dissemination, or local immune activation within the eschar. PMID:18505434

Autologous Stem Cells in Achilles Tendinopathy (ASCAT): protocol for a phase IIA, single-centre, proof-of-concept study

PubMed Central

Goldberg, Andrew J; Zaidi, Razi; Brooking, Deirdre; Kim, Louise; Korda, Michelle; Masci, Lorenzo; Green, Ruth; O’Donnell, Paul; Smith, Roger

2018-01-01

Introduction Achilles tendinopathy (AT) is a cause of pain and disability affecting both athletes and sedentary individuals. More than 150 000 people in the UK every year suffer from AT. While there is much preclinical work on the use of stem cells in tendon pathology, there is a scarcity of clinical data looking at the use of mesenchymal stem cells to treat tendon disease and there does not appear to be any studies of the use of autologous cultured mesenchymal stem cells (MSCs) for AT. Our hypothesis is that autologous culture expanded MSCs implanted into an area of mid-portion AT will lead to improved pain-free mechanical function. The current paper presents the protocol for a phase IIa clinical study. Methods and analysis The presented protocol is for a non-commercial, single-arm, open-label, phase IIa proof-of-concept study. The study will recruit 10 participants and will follow them up for 6 months. Included will be patients aged 18–70 years with chronic mid-portion AT who have failed at least 6 months of non-operative management. Participants will have a bone marrow aspirate collected from the posterior iliac crest under either local or general anaesthetic. MSCs will be isolated and expanded from the bone marrow. Four to 6 weeks after the harvest, participants will undergo implantation of the culture expanded MSCs under local anaesthetic and ultrasound guidance. The primary outcome will be safety as defined by the incidence rate of serious adverse reaction. The secondary outcomes will be efficacy as measured by patient-reported outcome measures and radiological outcome using ultrasound techniques. Ethics and dissemination The protocol has been approved by the National Research Ethics Service Committee (London, Harrow; reference 13/LO/1670). Trial findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT02064062. PMID:29764889

The Benefit of Microskin in Combination With Autologous Keratinocyte Suspension to Treat Full Skin Loss In Vivo.

PubMed

Yuru, Shang; Dawei, Li; Chuanan, Shen; Kai, Yin; Li, Ma; Longzhu, Li; Dongxu, Zhao; Wenfeng, Cheng

Patients with extensive deep burns often lack enough autologous skin to cover the wounds. This study explores a new method using microskin in combination with autologous keratinocytes in the treatment of extensive deep burn. Wounds in the combination group were treated with automicroskin at an area expansion ratio of 20:1 (wound area to automicroskin area) and autologous keratinocyte suspension, which were compared with the following treatments: no autotransplant, only allografts (control group); autologous keratinocyte suspension only (keratinocyte only group); automicroskin at an area expansion ratio of 20:1 (20:1 group); and automicroskin at an area expansion ratio of 10:1 (10:1 group, positive control). The authors used epithelialization rate (epithelialized area on day 21 divided by original wound area), hematoxylin and eosin staining, laminin, and type IV collagen immunohistochemistry to assess wound healing. The epithelialization rate of combination group (74.2% ± 8.0%) was similar to that of 10: 1 group (84.3% ± 11.9%, P = .085) and significantly (P < .05) higher than that of 20:1 group (59.2% ± 10.8%), keratinocyte only group (53.8% ± 11.5%), and control group (22.7% ± 5.5%). The hematoxylin and eosin staining and immunohistochemistry showed the epithelialization in the combination group was better than that in the keratinocyte only group and control group. Microskin in combination with autologous keratinocyte suspension can promote the reepithelialization of full-thickness wounds and reduce the requirements for automircoskin, and it is a useful option in the treatment of extensive deep burns.

Autologous bone marrow stem cell transplantation attenuates hepatocyte apoptosis in a rat model of ex vivo liver resection and liver autotransplantation.

PubMed

Xu, Tubing; Wang, Xiaojun; Chen, Geng; He, Yu; Bie, Ping

2013-10-01

To investigate the efficacy of autologous bone marrow stem cell (BMSC) transplantation in the treatment of hepatic injury in ex vivo liver resection and liver autotransplantation (ELRLA). Rat hepatic fibrosis was induced by intraperitoneal injection of 50% CCl4-olive oil solution at a dose of 2 mL/kg twice weekly for 4 wk. ELRLA was performed 3 d post the last injection of CCl4. Six rats in each group were killed 12, 24, 48, 72, and 168 h after the operation. Hepatocyte apoptosis was determined by TUNEL assay. The expression of Bcl-2, Bax, transforming growth factor (TGF) β1, TGFβ1 receptor1/2, and phosphorylated p38 MAPK were determined by Western blot. Autologous BMSC transplantation significantly inhibited the increase of alanine aminotransferease and aspartate aminotransferase at 12, 24, and 48 h post operation and attenuated ELRLA-induced hepatocyte apoptosis. In BMSC-treated rats, the expression of Bcl-2 was significantly upregulated, whereas there were no obvious changes in Bax level. The expression of TGFβ1 was significantly upregulated in the rat liver after the surgery. Autologous BMSC transplantation significantly downregulated the TGFβ1 levels at 48, 72, and 168 h post surgery. However, autologous BMSC transplantation showed little effect on the levels of TGFβ receptor 1/2 at all the time points observed. Furthermore, autologous BMSC transplantation significantly inhibited the activation of p38 MAPK. Autologous BMSC transplantation may reduce ELRLA-induced liver injury and improve survival rates in hepatic fibrosis rats. Autologous BMSC transplantation may be useful to improve the outcome of patients who undergo ELRLA. Copyright © 2013 Elsevier Inc. All rights reserved.

A prospective randomized trial comparing homologous and autologous fibrin sealants for the control of alveolar air leak

PubMed Central

Erşen, Ezel; Demirkaya, Ahmet; Kara, H. Volkan; Alizade, Nurlan; İşcan, Mehlika; Kaynak, Kamil; Turna, Akif

2017-01-01

Background Postoperative air leak is a common complication seen after pulmonary resection. It is a significant reason of morbidity and also leads to greater hospital cost owing to prolonged length of stay. The purpose of this study is to compare homologous sealant with autologous one to prevent air leak following pulmonary resection. Methods A total of 57 patients aged between 20 and 79 (mean age: 54.36) who underwent pulmonary resection other than pneumonectomy (lobar or sublobar resections) were analyzed. There were 47 males (83%) and 10 females (17%). Patients who intraoperatively had air leaks were randomized to receive homologous (Tisseel; n=28) or autologous (Vivostat; n=29) fibrin sealant. Differences among groups in terms of air leak, prolonged air leak, hospital stay, amount of air leak were analyzed. Results Indications for surgery were primary lung cancer in 42 patients (71.9%), secondary malignancy in 5 patients (8.8%), and benign disease in 10 patients (17.5%). Lobectomy was performed in 40 patients (70.2%), whereas 17 patients (29.8%) had wedge resection. Thirteen (46.4%) patients developed complications in patients receiving homologous sealant while 11 (38.0%) patients had complication in autologous sealant group (P=0.711). Median duration of air leak was 3 days in two groups. Time to intercostal drain removal was 3.39 and 3.38 days in homologous and autologous sealant group respectively (P=0.978). Mean hospital stay was 5.5 days in patients receiving homologous sealant whereas it was 5.0 days in patients who had autologous agent (P=0.140). There were no significant differences between groups in terms of measured maximum air leak (P=0.823) and mean air leak (P=0.186). There was no significant difference in the incidence of complications between two groups (P=0.711). Conclusions Autologous and heterologous fibrin sealants are safe and acts similarly in terms of air leak and hospital stay in patients who had resectional surgery. PMID:29221263

A prospective randomized trial comparing homologous and autologous fibrin sealants for the control of alveolar air leak.

PubMed

Kılıç, Burcu; Erşen, Ezel; Demirkaya, Ahmet; Kara, H Volkan; Alizade, Nurlan; İşcan, Mehlika; Kaynak, Kamil; Turna, Akif

2017-09-01

Postoperative air leak is a common complication seen after pulmonary resection. It is a significant reason of morbidity and also leads to greater hospital cost owing to prolonged length of stay. The purpose of this study is to compare homologous sealant with autologous one to prevent air leak following pulmonary resection. A total of 57 patients aged between 20 and 79 (mean age: 54.36) who underwent pulmonary resection other than pneumonectomy (lobar or sublobar resections) were analyzed. There were 47 males (83%) and 10 females (17%). Patients who intraoperatively had air leaks were randomized to receive homologous (Tisseel; n=28) or autologous (Vivostat; n=29) fibrin sealant. Differences among groups in terms of air leak, prolonged air leak, hospital stay, amount of air leak were analyzed. Indications for surgery were primary lung cancer in 42 patients (71.9%), secondary malignancy in 5 patients (8.8%), and benign disease in 10 patients (17.5%). Lobectomy was performed in 40 patients (70.2%), whereas 17 patients (29.8%) had wedge resection. Thirteen (46.4%) patients developed complications in patients receiving homologous sealant while 11 (38.0%) patients had complication in autologous sealant group (P=0.711). Median duration of air leak was 3 days in two groups. Time to intercostal drain removal was 3.39 and 3.38 days in homologous and autologous sealant group respectively (P=0.978). Mean hospital stay was 5.5 days in patients receiving homologous sealant whereas it was 5.0 days in patients who had autologous agent (P=0.140). There were no significant differences between groups in terms of measured maximum air leak (P=0.823) and mean air leak (P=0.186). There was no significant difference in the incidence of complications between two groups (P=0.711). Autologous and heterologous fibrin sealants are safe and acts similarly in terms of air leak and hospital stay in patients who had resectional surgery.

Autologous hematopoietic stem cells for refractory Crohn's disease.

PubMed

DiNicola, C A; Zand, A; Hommes, D W

2017-05-01

Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease. Clinical and endoscopic remission has been achieved in patients treated with AHSCT for CD. The only randomized trial published to date, the ASTIC Trial, did not support further use of AHSCT to treat CD. Yet, critics of this trial have deemed AHSCT as a promising treatment for severe refractory CD. Expert opinion: Even with the promising evidence presented for HSCT for refractory CD, protocols need to be refined through the collaboration of GI and hemato-oncology professionals. The goal is to incorporate safe AHSCT and restore tolerance by delivering an effective immune 'cease fire' as a treatment option for severe refractory CD.

Molecular cloning and expression of a unique receptor-like protein-tyrosine-phosphatase in the leucocyte-common-antigen-related phosphate family.

PubMed Central

Zhang, W R; Hashimoto, N; Ahmad, F; Ding, W; Goldstein, B J

1994-01-01

Protein-tyrosine-phosphatases (PTPases) have been implicated in the regulation of certain tyrosine kinase growth factor receptors in that they dephosphorylate the activated (autophosphorylated) form of the receptors. In order to identify PTPases that potentially act on receptor targets in liver, we used the human leucocyte common antigen-related PTPase (LAR) cDNA [Streuli, Krueger, Hall, Schlossman and Saito (1988) J. Exp. Med. 168, 1523-1530] and isolated two closely related transmembrane PTPase homologues from a rat hepatic cDNA library. Both PTPases had large extracellular domains that contained three immunoglobulin-like repeats and eight type-III fibronectin repeats. Both enzymes had tandem homologous PTPase domains following a single hydrophobic transmembrane domain. One sequence encoded the rat homologue of LAR. The second PTPase, designated LAR-PTP2, had 79 and 90% identity with rat LAR in the respective cytoplasmic PTPase domains, with only 57% sequence similarity in the extracellular domain. The catalytic domains of LAR and LAR-PTP2 prepared by bacterial expression were active in dephosphorylating a variety of phosphotyrosyl substrates but did not hydrolyse phosphoserine or phosphothreonine residues of labelled casein. Both enzymes exhibited rapid turnover numbers of 4-7 s-1 for myelin basic protein and 78-150 s-1 for derivatized lysozyme. LAR and LAR-PTP2 displayed similar PTPase activity towards the simultaneous dephosphorylation of receptors of intact insulin and epidermal growth factor from liver membranes. These data indicate that there is a family of LAR-related PTPases that may regulate the phosphorylation state of receptor tyrosine kinases in liver and other tissues. Images Figure 1 Figure 4 Figure 5 Figure 6 PMID:8068021

Manufacturing models permitting roll out/scale out of clinically led autologous cell therapies: regulatory and scientific challenges for comparability.

PubMed

Hourd, Paul; Ginty, Patrick; Chandra, Amit; Williams, David J

2014-08-01

Manufacturing of more-than-minimally manipulated autologous cell therapies presents a number of unique challenges driven by complex supply logistics and the need to scale out production to multiple manufacturing sites or near the patient within hospital settings. The existing regulatory structure in Europe and the United States imposes a requirement to establish and maintain comparability between sites. Under a single market authorization, this is likely to become an unsurmountable burden beyond two or three sites. Unless alternative manufacturing approaches can be found to bridge the regulatory challenge of comparability, realizing a sustainable and investable business model for affordable autologous cell therapy supply is likely to be extremely demanding. Without a proactive approach by the regulators to close this "translational gap," these products may not progress down the development pipeline, threatening patient accessibility to an increasing number of clinician-led autologous cellular therapies that are already demonstrating patient benefits. We propose three prospective manufacturing models for the scale out/roll out of more-than-minimally manipulated clinically led autologous cell therapy products and test their prospects for addressing the challenge of product comparability with a selected expert reference panel of US and UK thought leaders. This paper presents the perspectives and insights of the panel and identifies where operational, technological and scientific improvements should be prioritized. The main purpose of this report is to solicit feedback and seek input from key stakeholders active in the field of autologous cell therapy in establishing a consensus-based manufacturing approach that may permit the roll out of clinically led autologous cell therapies. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

The use of a national transplant registry to benchmark transplant outcome for patients undergoing autologous and allogeneic stem cell transplantation in the United Kingdom and Ireland.

PubMed

Russell, N H; Szydlo, R; McCann, S; Potter, M N; Craddock, C; Towlson, K; Apperley, J F

2004-02-01

As part of its clinical governance programme the British Society for Blood and Marrow Transplantation (BSBMT) undertook an analysis of transplant outcome for adults undergoing human leucocyte antigen - identical sibling allogeneic transplantation for chronic myeloid leukaemia (CML) in first chronic phase (CP1) or autologous transplantation for Hodgkin's disease (HD). The study aimed to compare transplant-related mortality (TRM) and survival for patients reported to the BSBMT with patients transplanted in the rest of Europe, reported to the European Group for Blood and Marrow Transplantation (EBMT). The outcomes for 104 allogeneic transplants for CML in 24 UK/Irish centres were compared with 775 allografts in 145 other European centres. For HD, 241 autografts from 38 UK/Irish centres were compared with 1145 transplants in 239 other European centres. For both diseases, the cohorts were broadly matched with the exception of CML, where 85% of patients were transplanted <1 year from diagnosis in the UK/Ireland compared with 68% in the EBMT (P = 0.001). Cox regression analysis was undertaken using known delineated variables affecting transplant outcome in addition to the registry of origin. The adjusted survival curves for CML showed no significant differences between the two groups, with 3-year survival probabilities of 70.2% and 67.1% for the EBMT and BSBMT cohorts respectively. Likewise, the analysis for HD showed overlapping survival curves, with 3-year survival probabilities of 71.8% (EBMT) and 70.8% (BSBMT). TRM was not statistically different in either disease. This study demonstrates the potential for using national registries to benchmark transplant outcome against the EBMT registry.

Preclinical Derivation and Imaging of Autologously Transplanted Canine Induced Pluripotent Stem Cells*

PubMed Central

Lee, Andrew S.; Xu, Dan; Plews, Jordan R.; Nguyen, Patricia K.; Nag, Divya; Lyons, Jennifer K.; Han, Leng; Hu, Shijun; Lan, Feng; Liu, Junwei; Huang, Mei; Narsinh, Kazim H.; Long, Charles T.; de Almeida, Patricia E.; Levi, Benjamin; Kooreman, Nigel; Bangs, Charles; Pacharinsak, Cholawat; Ikeno, Fumiaki; Yeung, Alan C.; Gambhir, Sanjiv S.; Robbins, Robert C.; Longaker, Michael T.; Wu, Joseph C.

2011-01-01

Derivation of patient-specific induced pluripotent stem cells (iPSCs) opens a new avenue for future applications of regenerative medicine. However, before iPSCs can be used in a clinical setting, it is critical to validate their in vivo fate following autologous transplantation. Thus far, preclinical studies have been limited to small animals and have yet to be conducted in large animals that are physiologically more similar to humans. In this study, we report the first autologous transplantation of iPSCs in a large animal model through the generation of canine iPSCs (ciPSCs) from the canine adipose stromal cells and canine fibroblasts of adult mongrel dogs. We confirmed pluripotency of ciPSCs using the following techniques: (i) immunostaining and quantitative PCR for the presence of pluripotent and germ layer-specific markers in differentiated ciPSCs; (ii) microarray analysis that demonstrates similar gene expression profiles between ciPSCs and canine embryonic stem cells; (iii) teratoma formation assays; and (iv) karyotyping for genomic stability. Fate of ciPSCs autologously transplanted to the canine heart was tracked in vivo using clinical positron emission tomography, computed tomography, and magnetic resonance imaging. To demonstrate clinical potential of ciPSCs to treat models of injury, we generated endothelial cells (ciPSC-ECs) and used these cells to treat immunodeficient murine models of myocardial infarction and hindlimb ischemia. PMID:21719696

Gastrocnemius tendon strain in a dog treated with autologous mesenchymal stem cells and a custom orthosis.

PubMed

Case, J Brad; Palmer, Ross; Valdes-Martinez, Alex; Egger, Erick L; Haussler, Kevin K

2013-05-01

To report clinical findings and outcome in a dog with gastrocnemius tendon strain treated with autologous mesenchymal stem cells and a custom orthosis. Clinical report. A 4-year-old spayed female Border Collie. Bone-marrow derived, autologous mesenchymal stem cells were transplanted into the tendon core lesion. A custom, progressive, dynamic orthosis was fit to the tarsus. Serial orthopedic examinations and ultrasonography as well as long-term force-plate gait analysis were utilized for follow up. Lameness subjectively resolved and peak vertical force increased from 43% to 92% of the contralateral pelvic limb. Serial ultrasonographic examinations revealed improved but incomplete restoration of normal linear fiber pattern of the gastrocnemius tendon. Findings suggest that autologous mesenchymal stem cell transplantation with custom, progressive, dynamic orthosis may be a viable, minimally invasive technique for treatment of calcaneal tendon injuries in dogs. © Copyright 2013 by The American College of Veterinary Surgeons.

Indications and organisational methods for autologous blood transfusion procedures in Italy: results of a national survey

PubMed Central

Catalano, Liviana; Campolongo, Alessandra; Caponera, Maurizio; Berzuini, Alessandra; Bontadini, Andrea; Furlò, Giuseppe; Pasqualetti, Patrizio; Liumbruno, Giancarlo M.

2014-01-01

Introduction Pre-operative donation of autologous blood is a practice that is now being abandoned. Alternative methods of transfusing autologous blood, other than predeposited blood, do however play a role in limiting the need for transfusion of allogeneic blood. This survey of autologous blood transfusion practices, promoted by the Italian Society of Transfusion Medicine and Immunohaematology more than 2 years after the publication of national recommendations on the subject, was intended to acquire information on the indications for predeposit in Italy and on some organisational aspects of the alternative techniques of autotransfusion. Materials and methods A structured questionnaire consisting of 22 questions on the indications and organisational methods of autologous blood transfusion was made available on a web platform from 15 January to 15 March, 2013. The 232 Transfusion Services in Italy were invited by e-mail to complete the online survey. Results Of the 232 transfusion structures contacted, 160 (69%) responded to the survey, with the response rate decreasing from the North towards the South and the Islands. The use of predeposit has decreased considerably in Italy and about 50% of the units collected are discarded because of lack of use. Alternative techniques (acute isovolaemic haemodilution and peri-operative blood salvage) are used at different frequencies across the country. Discussion The data collected in this survey can be considered representative of national practice; they show that the already very limited indications for predeposit autologous blood transfusion must be adhered to even more scrupulously, also to avoid the notable waste of resources due to unused units. Users of alternative autotransfusion techniques must be involved in order to gain a full picture of the degree of use of such techniques; multidisciplinary agreement on the indications for their use is essential in order for these indications to have an effective role in �

Indications and organisational methods for autologous blood transfusion procedures in Italy: results of a national survey.

PubMed

Catalano, Liviana; Campolongo, Alessandra; Caponera, Maurizio; Berzuini, Alessandra; Bontadini, Andrea; Furlò, Giuseppe; Pasqualetti, Patrizio; Liumbruno, Giancarlo M

2014-10-01

Pre-operative donation of autologous blood is a practice that is now being abandoned. Alternative methods of transfusing autologous blood, other than predeposited blood, do however play a role in limiting the need for transfusion of allogeneic blood. This survey of autologous blood transfusion practices, promoted by the Italian Society of Transfusion Medicine and Immunohaematology more than 2 years after the publication of national recommendations on the subject, was intended to acquire information on the indications for predeposit in Italy and on some organisational aspects of the alternative techniques of autotransfusion. A structured questionnaire consisting of 22 questions on the indications and organisational methods of autologous blood transfusion was made available on a web platform from 15 January to 15 March, 2013. The 232 Transfusion Services in Italy were invited by e-mail to complete the online survey. Of the 232 transfusion structures contacted, 160 (69%) responded to the survey, with the response rate decreasing from the North towards the South and the Islands. The use of predeposit has decreased considerably in Italy and about 50% of the units collected are discarded because of lack of use. Alternative techniques (acute isovolaemic haemodilution and peri-operative blood salvage) are used at different frequencies across the country. The data collected in this survey can be considered representative of national practice; they show that the already very limited indications for predeposit autologous blood transfusion must be adhered to even more scrupulously, also to avoid the notable waste of resources due to unused units.Users of alternative autotransfusion techniques must be involved in order to gain a full picture of the degree of use of such techniques; multidisciplinary agreement on the indications for their use is essential in order for these indications to have an effective role in "patient blood management" programmes.

Category labels versus feature labels: category labels polarize inferential predictions.

PubMed

Yamauchi, Takashi; Yu, Na-Yung

2008-04-01

What makes category labels different from feature labels in predictive inference? This study suggests that category labels tend to make inductive reasoning polarized and homogeneous. In two experiments, participants were shown two schematic pictures of insects side by side and predicted the value of a hidden feature of one insect on the basis of the other insect. Arbitrary verbal labels were shown above the two pictures, and the meanings of the labels were manipulated in the instructions. In one condition, the labels represented the category membership of the insects, and in the other conditions, the same labels represented attributes of the insects. When the labels represented category membership, participants' responses became substantially polarized and homogeneous, indicating that the mere reference to category membership can modify reasoning processes.

Anti-inflammatory lipocortin 1 production by peripheral blood leucocytes in response to hydrocortisone.

PubMed

Goulding, N J; Godolphin, J L; Sharland, P R; Peers, S H; Sampson, M; Maddison, P J; Flower, R J

1990-06-16

The presence and amount of the anti-inflammatory protein lipocortin 1 was determined in plasma and peripheral blood leucocytes by a highly specific, enzyme-linked immunosorbent assay. Within 120 min of a single intravenous dose of 100 mg hydrocortisone, the intracellular concentrations of lipocortin 1 in peripheral monocytes in 7 of 8 healthy men increased by a median of 225% (range 129-507%) compared with pretreatment levels, and mononuclear cell-surface lipocortin increased by a median of 224% (range 76-483%). Placebo injections had no effect. There was no increase at any time in free plasma or polymorph-associated lipocortin. In 3 of 4 subjects, induction of lipocortin was also observed when whole unseparated blood was incubated in vitro after steroid administration, but cells which had first been isolated and purified were refractory to such induction. Thus rapid changes in the concentration of an active anti-inflammatory protein can occur in man after normal therapeutic doses of hydrocortisone.

A Nationwide Analysis of Cost Variation for Autologous Free Flap Breast Reconstruction.

PubMed

Billig, Jessica I; Lu, Yiwen; Momoh, Adeyiza O; Chung, Kevin C

2017-11-01

Cost variation among hospitals has been demonstrated for surgical procedures. Uncovering these differences has helped guide measures taken to reduce health care spending. To date, the fiscal consequence of hospital variation for autologous free flap breast reconstruction is unknown. To investigate factors that influence cost variation for autologous free flap breast reconstruction. A secondary cross-sectional analysis was performed using the Healthcare Cost and Utilization Project National Inpatient Sample database from 2008 to 2010. The dates of analysis were September 2016 to February 2017. The setting was a stratified sample of all US community hospitals. Participants were female patients who were diagnosed as having breast cancer or were at high risk for breast cancer and underwent autologous free flap breast reconstruction. Variables of interest included demographic data, hospital characteristics, length of stay, complications (surgical and systemic), and inpatient cost. The study used univariate and generalized linear mixed models to examine associations between patient and hospital characteristics and cost. A total of 3302 patients were included in the study, with a median age of 50 years (interquartile range, 44-57 years). The mean cost for autologous free flap breast reconstruction was $22 677 (interquartile range, $14 907-$33 391). Flap reconstructions performed at high-volume hospitals were significantly more costly than those performed at low-volume hospitals ($24 360 vs $18 918, P < .001). Logistic regression demonstrated that hospital volume correlated with increased cost (Exp[β], 1.06; 95% CI, 1.02-1.11; P = .003). Fewer surgical complications (16.4% [169 of 1029] vs 23.7% [278 of 1174], P < .001) and systemic complications (24.2% [249 of 1029] vs 31.2% [366 of 1174], P < .001) were experienced in high-volume hospitals compared with low-volume hospitals. Flap procedures performed in the West were the most expensive ($28�

Injection Pharyngoplasty With Autologous Fat as Treatment for Stress Velopharyngeal Insufficiency in Brass and Woodwind Musicians.

PubMed

Syamal, Mausumi N; Bryson, Paul C

2017-02-01

Stress velopharyngeal insufficiency (SVPI) is an uncommon but often career-threatening condition affecting professional brass and woodwind musicians. To review the evaluation of and treatment for SVPI in professional musicians with lipoinjection to the posterior pharyngeal wall. A retrospective medical record and literature review. Two professional musicians with SVPI treated with autologous lipoinjection to the posterior pharyngeal wall were included. Nasopharyngoscopy was performed while patients played their instrument both before and after injection. To assess the effectiveness of autologous fat injection to the posterior pharyngeal wall to treat stress velopharyngeal insufficiency in 2 professional instrumentalists. Successful treatment was the absence of VPI during playing as visualized by flexible nasopharyngoscopy. After autologous lipoinjection of the posterior pharyngeal wall, 1 patient resumed full play with complete resolution, now 3 years after lipoinjection pharyngoplasty. The other patient received temporary resolution. Both had no surgical complications. Stress VPI is often a career-threatening condition for professional brass and woodwind musicians, with a cited incidence of 34%. Various treatment options in the literature include observation, speech and language pathology referral for pharyngeal strengthening, lipoinjection of the soft palate, and more invasive options, such as sphincter pharyngoplasty, pharyngeal flaps and V-Y pushback. Autologous fat injection pharyngoplasty of the posterior pharyngeal wall may be a less invasive treatment option for musicians with SVPI.

Nanofat-derived stem cells with platelet-rich fibrin improve facial contour remodeling and skin rejuvenation after autologous structural fat transplantation

PubMed Central

Liang, Zhi-Jie; Chen, Hai; Zhu, Mao-Guang; Xu, Fang-Tian; He, Ning; Wei, Xiao-Juan; Li, Hong-Mian

2017-01-01

Traditional autologous fat transplantation is a common surgical procedure for treating facial soft tissue depression and skin aging. However, the transplanted fat is easily absorbed, reducing the long-term efficacy of the procedure. Here, we examined the efficacy of nanofat-assisted autologous fat structural transplantation. Nanofat-derived stem cells (NFSCs) were isolated, mechanically emulsified, cultured, and characterized. Platelet-rich fibrin (PRF) enhanced proliferation and adipogenic differentiation of NFSCs in vitro. We then compared 62 test group patients with soft tissue depression or signs of aging who underwent combined nanofat, PRF, and autologous fat structural transplantation to control patients (77 cases) who underwent traditional autologous fat transplantation. Facial soft tissue depression symptoms and skin texture were improved to a greater extent after nanofat transplants than after traditional transplants, and the nanofat group had an overall satisfaction rate above 90%. These data suggest that NFSCs function similarly to mesenchymal stem cells and share many of the biological characteristics of traditional fat stem cell cultures. Transplants that combine newly-isolated nanofat, which has a rich stromal vascular fraction (SVF), with PRF and autologous structural fat granules may therefore be a safe, highly-effective, and long-lasting method for remodeling facial contours and rejuvenating the skin. PMID:28978136

Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study.

PubMed

Chiappella, Annalisa; Martelli, Maurizio; Angelucci, Emanuele; Brusamolino, Ercole; Evangelista, Andrea; Carella, Angelo Michele; Stelitano, Caterina; Rossi, Giuseppe; Balzarotti, Monica; Merli, Francesco; Gaidano, Gianluca; Pavone, Vincenzo; Rigacci, Luigi; Zaja, Francesco; D'Arco, Alfonso; Cascavilla, Nicola; Russo, Eleonora; Castellino, Alessia; Gotti, Manuel; Congiu, Angela Giovanna; Cabras, Maria Giuseppina; Tucci, Alessandra; Agostinelli, Claudio; Ciccone, Giovannino; Pileri, Stefano A; Vitolo, Umberto

2017-08-01

The prognosis of young patients with diffuse large B-cell lymphoma at high risk (age-adjusted International Prognostic Index [aa-IPI] score 2 or 3) treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) is poor. The aim of this study was to investigate the possible benefit of intensification with high-dose chemotherapy and autologous stem-cell transplantation as part of first-line treatment in these patients. We did a multicentre, open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design to compare, at two different R-CHOP dose levels, a full course of rituximab-dose-dense chemotherapy (no transplantation group) versus an abbreviated course of rituximab-dose-dense chemotherapy followed by consolidation with R-MAD (rituximab plus high-dose cytarabine plus mitoxantrone plus dexamethasone) and high-dose BEAM chemotherapy (carmustine, etoposide, cytarabine, and melphalan) plus autologous stem-cell transplantation (transplantation group) in young patients (18-65 years) with untreated high-risk diffuse large B-cell lymphoma (aa-IPI score 2-3). At enrolment, patients were stratified according to aa-IPI score and randomly assigned (1:1:1:1) to receive R-CHOP (intravenous rituximab 375 mg/m 2 , cyclophosphamide 750 mg/m 2 , doxorubicin 50 mg/m 2 , and vincristine 1·4 mg/m 2 on day 1, plus oral prednisone 100 mg on days 1-5) delivered in a 14-day cycle (R-CHOP-14) for eight cycles; high-dose R-CHOP-14 (R-MegaCHOP-14; R-CHOP-14 except for cyclophosphamide 1200 mg/m 2 and doxorubicin 70 mg/m 2 ) for six cycles; R-CHOP-14 for four cycles followed by R-MAD (intravenous rituximab 375 mg/m 2 on day 1 or 4 plus intravenous cytarabine 2000 mg/m 2 and dexamethasone 4 mg/m 2 every 12 h on days 1-3 plus intravenous mitoxantrone 8 mg/m 2 on days 1-3) plus BEAM (intravenous carmustine 300 mg/m 2 on day -7, intravenous cytarabine 200 mg/m 2 twice a day on days -6 to -3, intravenous etoposide 100 mg/m 2 twice a day on days -6

[Human herpesvirus-6 pneumonitis following autologous peripheral blood stem cell transplantation].

PubMed

Saitoh, Yuu; Gotoh, Moritaka; Yoshizawa, Seiichiro; Akahane, Daigo; Fujimoto, Hiroaki; Ito, Yoshikazu; Ohyashiki, Kazuma

2018-01-01

A-46-year-old man was diagnosed with peripheral T cell lymphoma, not otherwise specified. He achieved a complete remission after pirarubicin, cyclophosphamide, vincristine, and prednisolone (THP-COP) therapy and successful autologous peripheral blood stem-cell transplantation (AutoSCT). However, 6 months post AutoSCT, he complained of fever. Chest computed tomography of the patient displayed bilateral interstitial pneumonitis. Human herpesvirus-6 (HHV-6) DNA was detected in his bronchoalveolar lavage fluid. Therefore, the patient was confirmed for HHV-6 pneumonitis. The treatment with foscarnet was effective, and no relapse was noticed in the patient. Besides, we have experienced pneumonitis of unknown origin in some patients after autologous or allogeneic stem-cell transplantations. Moreover, most of the above patients were clinically diagnosed using serum or plasma markers. Therefore, examining respiratory symptoms after AutoSCT would enable a more accurate diagnosis as well as treatment of patients with HHV-6 pneumonitis.

Bioengineering a vaginal replacement using a small biopsy of autologous tissue.

PubMed

Dorin, Ryan P; Atala, Anthony; Defilippo, Roger E

2011-01-01

Many congenital and acquired diseases result in the absence of a normal vagina. Patients with these conditions often require reconstructive surgery to achieve satisfactory cosmesis and physiological function, and a variety of materials have been used as tissue sources. Currently employed graft materials such as collagen scaffolds and small intestine are not ideal in that they fail to mimic the physiology of normal vaginal tissue. Engineering of true vaginal tissue from a small biopsy of autologous vagina should produce a superior graft material for vaginal reconstruction. This review describes our current experience with the engineering of such tissue and its use for vaginal reconstruction in animal models. Our successful construction and implantation of neovaginas through tissue engineering techniques demonstrates the feasibility of similar endeavors in human patients. Additionally, the use of pluripotent stem cells instead of autologous tissue could provide an "off-the-shelf" tissue source for vaginal reconstruction.

Concentrated autologous plasma protein: a biochemically neutral solder for tissue welding.

PubMed

Stewart, R B; Bleustein, C B; Petratos, P B; Chin, K C; Poppas, D P; Kung, R T

2001-01-01

Xenographic or allographic serum protein solders used for laser welding may have immunologic and/or pathogenic complications. The objective of these studies was to develop a safe, autologous solder. Five methods of preparing concentrated autologous plasma protein solder (CAPPS) were evaluated. Next, the CAPPS was evaluated via (1) thermal denaturation studies using differential scanning calorimetry, (2) tissue welding studies to characterize both acute and healing properties. The optimal concentration method to produce CAPPS rapidly was a dialysis method using chemical (osmotic) forces. The CAPPS showed similar denaturation profiles to serum albumin (SA) solders. Acutely, CAPPS provided comparable breaking strengths to SA solders. At 7 days, there was no significant difference in breaking strength or histology between 50% human SA solder and CAPPS (using a porcine skin model). These studies demonstrate that the CAPPS system provides acceptable acute and chronic properties for laser welding. Copyright 2001 Wiley-Liss, Inc.

Second-degree burns with six etiologies treated with autologous noncultured cell-spray grafting.

PubMed

Esteban-Vives, Roger; Choi, Myung S; Young, Matthew T; Over, Patrick; Ziembicki, Jenny; Corcos, Alain; Gerlach, Jörg C

2016-11-01

Partial and deep partial-thickness burn wounds present a difficult diagnosis and prognosis that makes the planning for a conservative treatment versus mesh grafting problematic. A non-invasive treatment strategy avoiding mesh grafting is often chosen by practitioners based on their clinical and empirical evidence. However, a delayed re-epithelialization after conservative treatment may extend the patient's hospitalization period, increase the risk of infection, and lead to poor functional and aesthetic outcome. Early spray grafting, using non-cultured autologous cells, is under discussion for partial and deep partial-thickness wounds to accelerate the re-epithelialization process, reducing the healing time in the hospital, and minimizing complications. To address planning for future clinical studies on this technology, suitable indications will be interesting. We present case information on severe second-degree injuries after gas, chemical, electrical, gasoline, hot water, and tar scalding burns showing one patient per indication. The treatment results with autologous non-cultured cells, support rapid, uncomplicated re-epithelialization with aesthetically and functionally satisfying outcomes. Hospital stays averaged 7.6±1.6 days. Early autologous cell-spray grafting does not preclude or prevent simultaneous or subsequent traditional mesh autografting when indicated on defined areas of full-thickness injury. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Autologous cultured keratinocytes on porcine gelatin microbeads effectively heal chronic venous leg ulcers.

PubMed

Liu, Jin Yu; Hafner, Jürg; Dragieva, Galya; Seifert, Burkhardt; Burg, Günter

2004-01-01

We have established a specific bioreactor microcarrier cell culture system using porcine gelatin microbeads as carriers to produce autologous keratinocytes on a large scale. Moreover, we have shown that autologous keratinocytes can be cultured on porcine collagen pads, thereby forming a single cell layer. The objective of this study was to compare efficacy and safety of autologous cultured keratinocytes on microbeads and collagen pads in the treatment of chronic wounds. Fifteen patients with recalcitrant venous leg ulcers were assigned to three groups in a single-center, prospective, uncontrolled study: five underwent a single treatment with keratinocyte monolayers on collagen pads (group 1); another five received a single grafting with keratinocyte-microbeads (group 2); and the last five received multiple, consecutive applications of keratinocyte-microbeads 3 days apart (group 3). All patients were followed for up to 12 weeks. By 12 weeks, there was a mean reduction in the initial wound area of 50, 83, and 97 percent in the three groups, respectively. The changes in wound size were statistically significant between the first and third groups (p= 0.0003). Keratinocyte-microbeads proved to be more effective than keratinocyte monolayers on collagen pads when the former were applied every 3 days. Rapid availability within 10-13 days after skin biopsy and easy handling represent particular advantages.

An overview on autologous fibrin glue in bone tissue engineering of maxillofacial surgery

PubMed Central

Khodakaram-Tafti, Azizollah; Mehrabani, Davood; Shaterzadeh-Yazdi, Hanieh

2017-01-01

The purpose of this review is to have an overview on the applications on the autologous fibrin glue as a bone graft substitute in maxillofacial injuries and defects. A search was conducted using the databases such as Medline or PubMed and Google Scholar for articles from 1985 to 2016. The criteria were “Autograft,” “Fibrin tissue adhesive,” “Tissue engineering,” “Maxillofacial injury,” and “Regenerative medicine.” Bone tissue engineering is a new promising approach for bone defect reconstruction. In this technique, cells are combined with three-dimensional scaffolds to provide a tissue-like structure to replace lost parts of the tissue. Fibrin as a natural scaffold, because of its biocompatibility and biodegradability, and the initial stability of the grafted stem cells is introduced as an excellent scaffold for tissue engineering. It promotes cell migration, proliferation, and matrix making through acceleration in angiogenesis. Growth factors in fibrin glue can stimulate and promote tissue repair. Autologous fibrin scaffolds are excellent candidates for tissue engineering so that they can be produced faster, cheaper, and in larger quantities. In addition, they are easy to use and the probability of viral or prion transmission may be decreased. Therefore, autologous fibrin glue appears to be promising scaffold in regenerative maxillofacial surgery. PMID:28584530

Autologous Myoblast Transplantation for Oculopharyngeal Muscular Dystrophy: a Phase I/Iia Clinical Study

PubMed Central

Périé, Sophie; Trollet, Capucine; Mouly, Vincent; Vanneaux, Valérie; Mamchaoui, Kamel; Bouazza, Belaïd; Marolleau, Jean Pierre; Laforêt, Pascal; Chapon, Françoise; Eymard, Bruno; Butler-Browne, Gillian; Larghero, Jérome; St Guily, Jean Lacau

2014-01-01

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant genetic disease mainly characterized by ptosis and dysphagia. We conducted a phase I/IIa clinical study (ClinicalTrials.gov NCT00773227) using autologous myoblast transplantation following myotomy in adult OPMD patients. This study included 12 patients with clinical diagnosis of OPMD, indication for cricopharyngeal myotomy, and confirmed genetic diagnosis. The feasibility and safety end points of both autologous myoblast transplantation and the surgical procedure were assessed by videoendoscopy in addition to physical examinations. Potential therapeutic benefit was also assessed through videoendoscopy and videofluoroscopy of swallowing, quality of life score, dysphagia grade, and a drink test. Patients were injected with a median of 178 million myoblasts following myotomy. Short and long-term (2 years) safety and tolerability were observed in all the patients, with no adverse effects. There was an improvement in the quality of life score for all 12 patients, and no functional degradation in swallowing was observed for 10 patients. A cell dose-dependant improvement in swallowing was even observed in this study. This trial supports the hypothesis that a local injection of autologous myoblasts in the pharyngeal muscles is a safe and efficient procedure for OPMD patients. PMID:23831596

Autologous bone marrow transplantation in relapsed adult acute leukemia.

PubMed

Dicke, K A; Zander, A R; Spitzer, G; Verma, D S; Peters, L J; Vellekoop, L; Thomson, S; Stewart, D; Hester, J P; McCredie, K B

1979-01-01

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%), when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

Autologous bone marrow transplantation in relapsed adult acute leukemia.

PubMed

Dicke, K A; Zander, A R; Spitzer, G; Verma, D S; Peters, L; Vellekoop, L; Thomson, S; Stewart, D; McCredie, K B

1980-01-01

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%) when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

HER2-specific T cells target primary glioblastoma stem cells and induce regression of autologous experimental tumors.

PubMed

Ahmed, Nabil; Salsman, Vita S; Kew, Yvonne; Shaffer, Donald; Powell, Suzanne; Zhang, Yi J; Grossman, Robert G; Heslop, Helen E; Gottschalk, Stephen

2010-01-15

Glioblastoma multiforme (GBM) is the most aggressive human primary brain tumor and is currently incurable. Immunotherapies have the potential to target GBM stem cells, which are resistant to conventional therapies. Human epidermal growth factor receptor 2 (HER2) is a validated immunotherapy target, and we determined if HER2-specific T cells can be generated from GBM patients that will target autologous HER2-positive GBMs and their CD133-positive stem cell compartment. HER2-specific T cells from 10 consecutive GBM patients were generated by transduction with a retroviral vector encoding a HER2-specific chimeric antigen receptor. The effector function of HER2-specific T cells against autologous GBM cells, including CD133-positive stem cells, was evaluated in vitro and in an orthotopic murine xenograft model. Stimulation of HER2-specific T cells with HER2-positive autologous GBM cells resulted in T-cell proliferation and secretion of IFN-gamma and interleukin-2 in a HER2-dependent manner. Patients' HER2-specific T cells killed CD133-positive and CD133-negative cells derived from primary HER2-positive GBMs, whereas HER2-negative tumor cells were not killed. Injection of HER2-specific T cells induced sustained regression of autologous GBM xenografts established in the brain of severe combined immunodeficient mice. Gene transfer allows the reliable generation of HER2-specific T cells from GBM patients, which have potent antitumor activity against autologous HER2-positive tumors including their putative stem cells. Hence, the adoptive transfer of HER2-redirected T cells may be a promising immunotherapeutic approach for GBM.

A clinical study on the usefulness of autologous plasma filler in the treatment of nasolabial fold wrinkles.

PubMed

Choi, Young-Jun; Kim, Han-Saem; Min, Joon Hong; Nam, Jae-Hui; Lee, Ga-Young; Kim, Won-Serk

2017-06-01

Recently, the efficacy of autologous plasma filler for the reduction of facial wrinkles has been demonstrated. The aim of our study is to validate the efficacy and safety of autologous plasma filler in treating nasolabial fold wrinkles. Twenty Korean patients with moderate-to-severe nasolabial fold wrinkles were enrolled. The patients were treated with one session of autologous plasma filler. The wrinkle improvement effects were evaluated at 1-week, 4-week, 8-week, and 12-week after the treatment. Three assessment methods were applied. First, two independent dermatologists assessed cosmetic results using a 5-point wrinkle assessment scale. Second, global aesthetic improvement score was used for assessment of the final cosmetic results. Third, patient satisfaction was surveyed. Also, the adverse effects associated to treatment were observed. Mean age of the patients was 44.5 years. The average 5-point wrinkle assessment scale score was significantly improved at 1, 4, 8, and 12 weeks after treatment, comparing to before treatment (p < 0.01). The patients' average global aesthetic improvement score also indicated better cosmetic outcomes. The clinical improvement with sufficient patients' satisfaction and no significant adverse events demonstrated that novel autologous plasma filler could be considered as efficient and safety treatment option for nasolabial fold wrinkles.

The Results of Autologous Skin Test in Patients with Chronic Urticaria in Hamadan, Iran

PubMed Central

Safari, Mojgan; Sayemiri, Hooshyar

2016-01-01

Introduction The etiology of chronic urticaria is unknown in many cases. In this study, we demonstrated the presence of autoimmune antibodies in patients with chronic urticaria by using of the Autologous Serum Skin Test (ASST). Methods We performed a cross-sectional study to detect the presence of autologous antibodies in the serum of 38 patients (25 females and 13 males) with idiopathic chronic urticaria who were referred to the Hamedan Allergy Clinic in 2014. All of the necessary tests for demonstrating chronic urticaria were performed, including complete blood count (CBC), thyroid and liver functionality tests, and the prick test but they did not confirm the cause of chronic urticaria. We conducted the Autologous Serum Skin Test on the patients and analyzed the results. Results In 15 patients (39%), the ASST was positive. Of the 15 patients with positive autoimmune chronic urticaria, five patients (33%) were males, and 10 patients (67%) were females. Conclusion We concluded that many patients with chronic urticaria have autoimmune urticaria. It is the reason for the lack of the response to treatment with common medications for urticaria. New ways of treatment must be considered for them. PMID:27504169

Establishment of autologous embryonic stem cells derived from preantral follicle culture and oocyte parthenogenesis.

PubMed

Lee, Seung Tae; Choi, Mun Hwan; Lee, Eun Ju; Gong, Seung Pyo; Jang, Mi; Park, Sang Hyun; Jee, Hyang; Kim, Dae Yong; Han, Jae Yong; Lim, Jeong Mook

2008-11-01

To evaluate whether autologous embryonic stem cells can be established without generating clone embryos. Prospective model study. Gamete and stem cell biotechnology laboratory in Seoul National University, Seoul, Korea. F1 hybrid B6D2F1 mice. Preantral follicles were cultured, and oocytes matured in the follicles were parthenogenetically activated. Preimplantation development and stem cell characterization. More intrafollicular oocytes that were retrieved from secondary follicles matured and developed into blastocysts after parthenogenesis than those that were retrieved from primary follicles. Of those 35 blastocysts derived from 193 parthenotes, one line of colony-forming cells was established from the culturing of early secondary follicles. The established cells were positive for embryonic stem cell-specific markers and had normal diploid karyotype and telomerase activity. They differentiated into embryoid bodies in vitro and teratomas in vivo. Inducible differentiation of the established cells into neuronal lineage cells also was possible. Autologous embryonic stem cells can be established by preantral follicle culture and oocyte parthenogenesis. A combined technique of follicle culture and oocyte parthenogenesis that does not use developmentally competent oocytes has the potential to replace somatic cell nuclear transfer for autologous cell therapy.

Measurement of sulphated glycosaminoglycans production after autologous 'chondrocytes-fibrin' constructs implantation in sheep knee joint.

PubMed

Munirah, S; Samsudin, O C; Chen, H C; Salmah, S H Sharifah; Aminuddin, B S; Ruszymah, B H I

2008-07-01

Chondrocytes were isolated from articular cartilage biopsy and were cultivated in vitro. Approximately 30 million of cultured chondrocytes per ml were incorporated with autologous plasma-derived fibrin to form three-dimensional construct. Full-thickness punch hole defects were created in lateral and medial femoral condyles. The defects were implanted either with the autologous 'chondrocytes-fibrin' construct (ACFC), autologous chondrocytes (ACI) or fibrin blank (AF). Sheep were euthanized after 12 weeks. The gross morphology of all defects treated with ACFC implantation, ACI and AF exhibited median scores which correspond to a nearly normal appearance according to the International Cartilage Repair Society (ICRS) classification. ACFC significantly enhanced cartilage repair compared to ACI and AF in accordance with the modified O'Driscoll histological scoring scale. The relative sulphated glycosaminoglycans content (%) was significantly higher (p < 0.05) in ACFC when compared to control groups; ACI vs. fibrin only vs. untreated (blank). Results showed that ACFC implantation exhibited superior cartilage-like tissue regeneration compared to ACI. If the result is applicable to the human, it possibly will improve the existing treatment approaches for cartilage restoration in orthopaedic surgery.

Preclinical safety studies on autologous cultured human skin fibroblast transplantation.

PubMed

Zeng, Wei; Zhang, Shuying; Liu, Dai; Chai, Mi; Wang, Jiaqi; Zhao, Yuming

2014-01-01

Recently, FDA approved the clinical use of autologous fibroblasts (LAVIV™) for the improvement of nasolabial fold wrinkles in adults. The use of autologous fibroblasts for the augmentation of dermal and subcutaneous defects represents a potentially exciting natural alternative to the use of other filler materials for its long-term corrective ability and absence of allergic adverse effects proved by clinical application. However, compared to the clinical evidence, preclinical studies are far from enough. In this study, human skin-derived fibroblasts were cultured and expanded for both in vitro and in vivo observations. In vitro, the subcultured fibroblasts were divided into two groups. One set of cells underwent cell cycle and karyotype analysis at passages 5 and 10. The second group of cells was cocultured in medium with different concentrations of human skin extract D for the measurement of collagen concentration and cell count. In vivo, the subcultured fibroblasts were injected into nude mice subcutaneously. Biopsies were taken for morphology observation and specific collagen staining at 1, 2, and 3 months after injection. The results in vitro showed no significant differences in cell cycle distribution between passages 5 and 10. Cell proliferation and secretion were inhibited as the concentration of extract D increased. In vivo, the fibroblasts were remarkably denser on the experimental side with no dysplastic cells. Mitotic cells were easily observed at the end of the first month but were rare at the end of the third month. Type III collagen was detected at the end of the first month, while collagen type I was positive at the end of the second month. The content of both collagens increased as time passed. The above results indicated that the use of the autologous fibroblasts was safe, providing a basic support for clinical use of fibroblasts.

Outcomes of rotator cuff augmentation surgery with autologous fascia lata.

PubMed

Rosales-Varo, A P; García-Espona, M A; Roda-Murillo, O

To evaluate whether augmentation grafts using autologous fascia lata improve functional results for rotator cuff repairs and reduce the retear rate compared to those without augmentation. This is a prospective evaluation comprising 20 patients with a complete symptomatic rotator cuff tear. The operations were carried out from a superior approach performing a total cuff repair, for 10 patients we used a suture augmented with an autologous graft taken from their own fascia lata while unaugmented sutures were used for the other 10 patients. The follow-up period lasted for one year post-intervention. We measured variables for tear type, functionality and pain, both baseline and at 6 and 12-month follow ups. We evaluated retear incidence in each group as well as each group's pain and functionality response. The improved pain levels in the non-graft group evolved gradually over time. Conversely, in the group with the augmentation grafts, average Constant-Murley shoulder outcome scores at six months were already above 10 and were maintained at 12 months. One retear occurred in the graft group and 2 in the group without grafts, thus presenting no significant differences. There were no significant changes in pain and function values at the one year follow up in either group. Our preliminary results regarding rotator cuff augmentation surgery with autologous fascia lata showed a significant improvement in pain levels after 6 months compared to the patients with no augmentation, who required 12 months to reach the same values. After a year of follow up, there were no differences between the mean Constant and pain scores in either intervention group The number of retears in the non-graft group was greater than that in the group with grafts although the difference was not significant. Copyright © 2018 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Use of autologous human mesenchymal stromal cell/fibrin clot constructs in upper limb non-unions: long-term assessment.

PubMed

Giannotti, Stefano; Trombi, Luisa; Bottai, Vanna; Ghilardi, Marco; D'Alessandro, Delfo; Danti, Serena; Dell'Osso, Giacomo; Guido, Giulio; Petrini, Mario

2013-01-01

Tissue engineering appears to be an attractive alternative to the traditional approach in the treatment of fracture non-unions. Mesenchymal stromal cells (MSCs) are considered an appealing cell source for clinical intervention. However, ex vivo cell expansion and differentiation towards the osteogenic lineage, together with the design of a suitable scaffold have yet to be optimized. Major concerns exist about the safety of MSC-based therapies, including possible abnormal overgrowth and potential cancer evolution. We examined the long-term efficacy and safety of ex vivo expanded bone marrow MSCs, embedded in autologous fibrin clots, for the healing of atrophic pseudarthrosis of the upper limb. Our research work relied on three main issues: use of an entirely autologous context (cells, serum for ex vivo cell culture, scaffold components), reduced ex vivo cell expansion, and short-term MSC osteoinduction before implantation. Bone marrow MSCs isolated from 8 patients were expanded ex vivo until passage 1 and short-term osteo-differentiated in autologous-based culture conditions. Tissue-engineered constructs designed to embed MSCs in autologous fibrin clots were locally implanted with bone grafts, calibrating their number on the extension of bone damage. Radiographic healing was evaluated with short- and long-term follow-ups (range averages: 6.7 and 76.0 months, respectively). All patients recovered limb function, with no evidence of tissue overgrowth or tumor formation. Our study indicates that highly autologous treatment can be effective and safe in the long-term healing of bone non-unions. This tissue engineering approach resulted in successful clinical and functional outcomes for all patients.

The significance of hypersensitivity to autologous sweat and serum in cholinergic urticaria: cholinergic urticaria may have different subtypes.

PubMed

Kim, Jung Eun; Jung, Kwan Ho; Cho, Hyun Hee; Kang, Hoon; Park, Young Min; Park, Hyun Jeong; Lee, Jun Young

2015-07-01

The pathogenesis of cholinergic urticaria (ChU) has been unclear except for the involvement of acetylcholine. Attempts to classify ChU according to etiology have rarely been performed. To evaluate the significance of responsiveness to autologous sweat and serum in ChU in relation to their clinical characteristics. This study involved 18 patients diagnosed with ChU between January 2010 and April 2011 in the Catholic Medical Center-St. Paul's Hospital. History taking included symptom duration, association with atopy, decreased sweat secretions, seasonal variation, and response to treatment. Intradermal autologous serum skin test (ASST) and autologous sweat skin test (ASwST) and basophil histamine release test with sweat were done. Sweat hypersensitivity was proven by a positive ASwST and basophil histamine release test in only 37.5% of patients with ChU, and in none of the healthy controls. The weal size of ASwST correlated with percentage basophil histamine release. A positive response to autologous serum was displayed by 38.9% of patients, whereas 10% of healthy controls showed a positive ASST response. Intriguingly, patients with a positive ASwST had a negative ASST, and vice versa. Despite this, there was no difference in the clinical characteristics between positive ASST and positive ASwST groups. The frequency of hypersensitivity to autologous sweat and serum was significantly higher in patients with ChU, compared with healthy controls. This suggests that autoimmunity to an unknown serum factor as well as sweat hypersensitivity may be involved in the pathogenesis of ChU. © 2014 The International Society of Dermatology.

Autologous blood preparations rich in platelets, fibrin and growth factors.

PubMed

Fioravanti, C; Frustaci, I; Armellin, E; Condò, R; Arcuri, C; Cerroni, L

2015-01-01

Bone regeneration is often needed prior to dental implant treatment due to the lack of adequate quantity and quality after infectious diseases. The greatest regenerative power was obtained with autologous tissue, primarily the bone alive, taken from the same site or adjacent sites, up to the use centrifugation of blood with the selection of the parts with the greatest potential regenerative. In fact, various techniques and technologies were chronologically successive to cope with an ever better preparation of these concentrates of blood. Our aim is to review these advances and discuss the ways in which platelet concentrates may provide such unexpected beneficial therapeutic effects. The research has been carried out in the MEDLINE and Cochrane Central Register of Controlled Trials database by choosing keywords as "platelet rich plasma", "platelet rich fibrin", "platelet growth factors", and "bone regeneration" and "dentistry". Autologous platelet rich plasma is a safe and low cost procedure to deliver growth factors for bone and soft tissue healing. The great heterogeneity of clinical outcomes can be explained by the different PRP products with qualitative and quantitative difference among substance.

Evaluation of C3a receptor expression on human leucocytes by the use of novel monoclonal antibodies

PubMed Central

ZWIRNER, J; GÖTZE, O; BEGEMANN, G; KAPP, A; KIRCHHOFF, K; WERFEL, T

1999-01-01

Varying results have been published in the past regarding the reactivity of different leucocyte subpopulations, including neutrophils, monocytes and B lymphocytes, to the anaphylatoxin C3a and its degradation product C3a(desArg). To better characterize the cellular distribution of C3a receptor (C3aR) expression, monoclonal antibodies against two different epitopes on the third extracellular domain of the human C3aR were generated. Quantification of C3aR as compared with C5aR densities was performed on peripheral blood leucocytes by quantitative indirect immunofluorescence. Eosinophils and basophils expressed similar numbers of C3aR and C5aR molecules/cell. On eosinophils 10 700±4500 (mean±SD) C3aR and 14 700±4100 C5aR were found, whereas basophils carried 8100±2100 C3aR and 13 500±3800 C5aR. Monocytes expressed approximately six times more C5aR than C3aR molecules on their surface (6000±2500 C3aR versus 34 100±9300 C5aR molecules) whereas on neutrophils, the expression of C5aR was more than 20 times higher than the expression of C3aR (3100±1000 C3aR versus 63 500±12 200 C5aR). No C3aR expression was detectable on peripheral blood-derived B lymphocytes and on tonsillar B cells before and after stimulation with interleukin-2/Staphylococcus aureus Cowan strain I. Our findings correspond well with the paucity of data on C3a-induced functional activities in monocytes and neutrophils and suggest that eosinophilic and basophilic granulocytes represent the primary effector cells in the peripheral blood which can be stimulated by C3a. PMID:10447728

Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Puente, Pilar de la, E-mail: pilardelapuentegarcia@gmail.com; Ludeña, Dolores; López, Marta

2013-02-01

Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12more » pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.« less

Storage Duration of Autologous Stem Cell Preparations Has No Impact on Hematopoietic Recovery after Transplantation.

PubMed

Lisenko, Katharina; Pavel, Petra; Kriegsmann, Mark; Bruckner, Thomas; Hillengass, Jens; Goldschmidt, Hartmut; Witzens-Harig, Mathias; Ho, Anthony D; Wuchter, Patrick

2017-04-01

Peripheral blood stem cells (PBSCs) are widely used for autologous blood stem cell transplantation (ABSCT). These cells must be stored for months or even years, usually at temperatures ≤-140°C, until their use. Although several in vitro studies on CD34 + viability and clonogenic assays of PBSCs after long-term storage have been reported, only a few publications have investigated the influence of long-term storage on in vivo hematopoietic reconstitution. In this study, we retrospectively analyzed hematopoietic recovery after storage of PBSCs via controlled-rate freezing (CRF) and cryostorage in 10% DMSO at ≤-140°C in 105 patients with multiple myeloma who received high-dose melphalan before ABSCT. Three groups of PBSC transplantation (n = 247) were delineated based on the storage period: short-term (≤12 months, n = 143), medium-term (>12 and ≤60 months, n = 75), and long-term storage (>60 months, n = 29). A neutrophil increase of ≥.5 × 10 9 /L in medium-term or long-term PBSC cryopreservation groups was observed at day 14 after ABSCT; this increase was comparable to patients who received briefly stored PBSCs (day 15). No negative effect of PBSC storage duration was observed on leucocyte or neutrophil reconstitution. Platelet reconstitutions of ≥20  × 10 9 /L and 50 × 10 9 /L were observed after median times of 10 to 11 and 13 to 14 days after ABSCT, respectively. No influence of PBSC storage duration on platelet recovery of ≥20  × 10 9 /L and ≥50 × 10 9 /L was observed in the 3 storage groups (P = .07, P = .32). The number of previous ABSCTs also had no significant impact upon hematopoietic reconstitution. In conclusion, these results indicate that long-term cryopreservation of PBSC products at vapor nitrogen temperature after CRF does not have a negative effect on hematopoietic recovery even after prolonged storage. Copyright © 2017 The American Society for Blood and Marrow Transplantation

Fibrin glue versus autologous blood for conjunctival autograft fixation in pterygium surgery.

PubMed

Boucher, Sophie; Conlon, Ronan; Teja, Salina; Teichman, Joshua C; Yeung, Season; Ziai, Setareh; Baig, Kashif

2015-08-01

To compare the outcomes between autologous blood- and fibrin glue-fixated conjunctival autografts in pterygium excision surgery. Retrospective case series. Forty eyes of 40 patients who had a primary nasal pterygium excision. A retrospective comparative case series of 40 eyes (40 patients) that had a primary nasal pterygium excision. All eyes had a conjunctival autograft from the superior bulbar conjunctiva to cover the scleral bed. Twenty eyes (20 patients) had fixation of the autograft using autologous blood (AB), and 20 eyes (20 patients) had fixation using fibrin glue (FG). One year of follow-up data included conjunctival graft stability (graft loss, graft retraction), pterygium recurrence, visual acuity, and postoperative complications. Descriptive and inferential statistics were performed. Intraoperatively, no complications occurred in either group. Graft loss occurred in 6 patients in the AB group, compared with none in the FG group. Graft retraction occurred in 3 patients in the AB group and 2 patients in the FG group. At 1 year postoperatively, pterygium recurrence occurred in 4 patients in the AB group and 1 patient in the FG group. One patient in the AB group developed a small pyogenic granuloma that resolved by 6 months with conservative management. Visual acuity remained stable in both groups. Conjunctival autograft fixation with autologous blood resulted in less stable conjunctival autografts and a higher recurrence rate compared with fixation with fibrin glue. Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Alterations in leucocyte subsets and histomorphology in normal-appearing perilesional skin and early and chronic hidradenitis suppurativa lesions.

PubMed

van der Zee, H H; de Ruiter, L; Boer, J; van den Broecke, D G; den Hollander, J C; Laman, J D; Prens, E P

2012-01-01

Current insight into the histopathological course of events during disease progression in hidradenitis suppurativa (HS) is fragmentary. To identify histological alterations and leucocyte subsets in normal-appearing perilesional skin, and early and chronic HS lesions. In this observational study we examined eight perilesional skin samples, and six early and 10 chronic prototypic HS lesions, as well as skin samples from four healthy donors using in situ immunostaining. Perilesional skin showed mild psoriasiform hyperplasia and follicular plugging as well as a low-grade influx of tryptase-positive mast cells, CD3+ T cells, CD138+ plasma cells and factor XIIIa+ dendritic cells. In early HS lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominated. In chronic disease, the infiltrate expanded with markedly increased frequencies of CD20+ and CD79a+ B cells and CD138+ plasma cells. As in early lesions, free keratin fibres were detected in the dermis and within giant cells. Single detached keratinocytes and strands of follicular epithelium were observed in the dermis, the latter frequently expressing Ki67, indicative of active proliferation. Psoriasiform hyperplasia, follicular plugging and low-grade leucocytic infiltration are already present in normal-appearing perilesional skin. Keratin fibres in the dermis are associated with clinical disease. Early lesions are characterized by neutrophilic abscess formation and influx of mainly histiocytes, and chronic lesions mainly by expansion of B cells and plasma cells in 'pseudo' follicles. Proliferating strands of follicular epithelium may initiate fistula formation. Mast cells are increased in all stages of HS including perilesional skin. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Alteration of Skin Properties with Autologous Dermal Fibroblasts

PubMed Central

Thangapazham, Rajesh L.; Darling, Thomas N.; Meyerle, Jon

2014-01-01

Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA) while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices. PMID:24828202

Calculations for reproducible autologous skin cell-spray grafting.

PubMed

Esteban-Vives, Roger; Young, Matthew T; Zhu, Toby; Beiriger, Justin; Pekor, Chris; Ziembicki, Jenny; Corcos, Alain; Rubin, Peter; Gerlach, Jörg C

2016-12-01

Non-cultured, autologous cell-spray grafting is an alternative to mesh grafting for larger partial- and deep partial-thickness burn wounds. The treatment uses a suspension of isolated cells, from a patient's donor site skin tissue, and cell-spray deposition onto the wound that facilitates re-epithelialization. Existing protocols for therapeutic autologous skin cell isolation and cell-spray grafting have defined the donor site area to treatment area ratio of 1:80, substantially exceeding the coverage of conventional mesh grafting. However, ratios of 1:100 are possible by maximizing the wound treatment area with harvested cells from a given donor site skin tissue according to a given burn area. Although cell isolation methods are very well described in the literature, a rational approach addressing critical aspects of these techniques are of interest in planning clinical study protocols. We considered in an experimental study the cell yield as a function of the donor site skin tissue, the cell density for spray grafting, the liquid spray volume, the sprayed distribution area, and the percentage of surface coverage. The experimental data was then used for the development of constants and mathematical equations to give a rationale for the cell isolation and cell-spray grafting processes and in planning for clinical studies. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Pulmonary deposition and disappearance of aerosolised secretory leucocyte protease inhibitor.

PubMed Central

Stolk, J.; Camps, J.; Feitsma, H. I.; Hermans, J.; Dijkman, J. H.; Pauwels, E. K.

1995-01-01

BACKGROUND--The neutrophil elastase inhibitor, secretory leucocyte protease inhibitor (SLPI), is a potential therapeutic tool in inflammatory lung diseases such as cystic fibrosis and pulmonary emphysema. The distribution and disappearance in the lung of aerosolised recombinant SLPI (rSLPI) was investigated in healthy humans and in patients with cystic fibrosis or alpha 1-antitrypsin-associated emphysema. METHODS--To distinguish aerosolised rSLPI from endogenous SLPI the recombinant inhibitor was radiolabelled with 99m-technetium (99mTc) pertechnetate. Distribution and disappearance of aerosolised 99mTc-rSLPI in the lungs were studied by gamma radiation imaging. RESULTS--The deposition of 99mTc-rSLPI in normal volunteers was homogeneous in all lung lobes, while in patients with cystic fibrosis or emphysema only well ventilated areas showed deposition of the aerosol. The disappearance rate of 99mTc-rSLPI was biexponential. The half life of the rapid phase was 0.2-2.8 hours, while that of the slow phase was more than 24 hours. CONCLUSIONS--Future aerosol therapy with rSLPI will be most beneficial for well ventilated lung tissue that needs protection against neutrophil derived elastase. It may be more difficult to neutralise the burden of elastase in poorly ventilated, highly inflamed areas as are seen in cystic fibrosis. Images PMID:7638807

Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS

PubMed Central

Madigan, Nicolas N.; Morris, Jonathan; Jentoft, Mark; Sorenson, Eric J.; Butler, Greg; Gastineau, Dennis; Dietz, Allan; Windebank, Anthony J.

2016-01-01

Objective: To determine the safety of intrathecal autologous adipose-derived mesenchymal stromal cell treatment for amyotrophic lateral sclerosis (ALS). Methods: Participants with ALS were enrolled and treated in this phase I dose-escalation safety trial, ranging from 1 × 107 (single dose) to 1 × 108 cells (2 monthly doses). After intrathecal treatments, participants underwent standardized follow-up, which included clinical examinations, revised ALS Functional Rating Scale (ALSFRS-R) questionnaire, blood and CSF sampling, and MRI of the neuroaxis. Results: Twenty-seven patients with ALS were enrolled and treated in this study. The safety profile was positive, with the most common side effects reported being temporary low back and radicular leg pain at the highest dose level. These clinical findings were associated with elevated CSF protein and nucleated cells with MRI of thickened lumbosacral nerve roots. Autopsies from 4 treated patients did not show evidence of tumor formation. Longitudinal ALSFRS-R questionnaires confirmed continued progression of disease in all treated patients. Conclusions: Intrathecal treatment of autologous adipose-derived mesenchymal stromal cells appears safe at the tested doses in ALS. These results warrant further exploration of efficacy in phase II trials. Classification of evidence: This phase I study provides Class IV evidence that in patient with ALS, intrathecal autologous adipose-derived mesenchymal stromal cell therapy is safe. PMID:27784774

The spontaneous return of sensibility in breasts reconstructed with autologous tissues.

PubMed

Shaw, W W; Orringer, J S; Ko, C Y; Ratto, L L; Mersmann, C A

1997-02-01

Some spontaneous return of sensibility following autologous tissue breast reconstruction is often suspected but not well documented. In the present study, objective touch-pressure, pain, temperature, and vibratory sensibilities were recorded in 33 autologous breast reconstructions at an average of 25.2 months postoperatively. Correlation of the sensory return with patients' satisfaction toward reconstruction was done by a detailed questionnaire. All except one patient regained a variety of sensibilities touch pressure in 97 percent of patients (averaging 81.05 gm/mm2 versus control of 7.98 gm/mm2), pain in 88 percent of patients, heat in 64 percent of patients (45 percent of quadrants), cold in 82 percent of patients (67 percent of quadrants), and high- and low-frequency vibration in 100 percent of patients (high in 90 percent of quadrants, low in 96 percent). Subjectively, 94 percent considered their chest comfortable to touch following reconstruction compared with 34 percent following mastectomy. On a scale from 1 to 10, patients rated their reconstructions an average of 9.3. Our findings confirm the spontaneous return of sensibility following a variety of autologous tissue breast reconstructions. The value of the sensory return is suggested by the high degree of satisfaction in nearly all patients. Further attempts to correlate the degree of sensory return with the degree of satisfaction were inconclusive because of the uniformly high satisfaction reported by the patients. The mechanism of reinnervation appears to come both from the skin margins and from the deep surface of the flap. Future developments in breast reconstruction should take into consideration the eventual quality of sensory return.

Autologous breast reconstruction using the immediately lipofilled extended latissimus dorsi flap.

PubMed

Johns, N; Fairbairn, N; Trail, M; Ewing, A; Yong, L; Raine, C; Dixon, J M

2018-02-01

The latissimus dorsi flap is a popular choice for autologous breast reconstruction. To dramatically improve volume, we report our experience of using the immediately lipofilled extended latissimus dorsi (ELD) flap and show it as a valid option for autologous breast reconstruction. Patients undergoing the procedure between December 2013 and June 2016 were included. Demographic, clinical and operative factors were analysed, together with in-hospital morbidity and duration of postoperative hospital stay. A total of 71 ELD flaps with immediate lipofilling were performed. Forty-five reconstructions were immediate and the remaining 26 delayed. Median (range) volume of autologous fat injected immediately was 171 ml (40-630 ml). Contralateral reductions were performed in 25 patients with the median reduction volume 185 g (89-683 g). Median duration of admission was 6.5 (3-18) days and patients were followed up for 12 months (1-37). Three total flap failures occurred and had to be excised (4%). One haematoma occurred requiring drainage (1%). Signs of infection requiring intravenous antibiotics occurred in five patients (7%). In 5 patients wound dehiscence occurred, and only two of these required resuturing (3%). In total, 7 patients developed a seroma requiring repeated drainage (10%). Three reconstructions experienced mild mastectomy flap necrosis with no needing reoperation (4%). Our experience represents the largest series to date and shows that in carefully selected patients the technique is safe, can avoid the requirement for implants, and has the potential to streamline the reconstructive journey. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Proof of concept of a new autologous skin substitute for the treatment of deep wounds in dogs.

PubMed

Ramió-Lluch, L; Cerrato, S; Brazis, P; Rabanal, R M; Fondevila, D; Puigdemont, A

2017-12-01

Autologous skin grafts are effective for the repair of large skin wounds, but the availability of large amounts of skin is often limited. Through bioengineering, several autologous skin substitutes have been developed for use in human clinical practice. However, few skin substitutes are available for use in animals. The aim of this study was to develop and assess an engineered autologous skin substitute for the treatment of deep wounds in veterinary medicine. Canine keratinocytes and fibroblasts were isolated after double enzyme digestion from 8mm punch biopsies from four healthy Beagle dogs. Skin substitutes were constructed on a fibrin-based matrix and grafting capacity was assessed by xenografting in six athymic mice. Bioengineered autologous skin was assessed clinically in two dogs with large deep skin wounds. The canine skin construct was ready for use within 12-14days after the initial biopsy specimens were obtained. Grafting capacity in this model was confirmed by successful grafting of the construct in athymic mice. In both dogs, grafts were established and permanent epithelialisation occurred. Histological studies confirmed successful grafting. This full thickness skin substitute developed for the management of large skin defects in dogs appears to be a safe and useful tool for clinical veterinary practice. Further studies are needed to validate its efficacy for the treatment of deep wounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel autologous stem cell procedure for the treatment of aplastic anaemia using reprogrammed mature adult cells: a pilot study

PubMed Central

Abuljadayel, Ilham Saleh; Mohanty, Dipika; Suri, Rajendar K.

2012-01-01

Background & objectives: Aplastic anaemia is a life threatening rare bone marrow failure disorder. The underlying haematopoietic cellular deficit leads to haemorrhage, infection and severe anaemia. The treatment of choice for this haematological condition is allogeneic bone marrow transplantation from fully matched HLA sibling. Though this procedure is curative in the majority of young patients with aplastic anaemia, extending this benefit to older patients or those lacking a family donor remains a major challenge. Herein, the safety and efficacy of infusing autologous retrodifferentiated haematopoietic stem cells (RHSC) into four patients with aplastic anaemia without the use of any pre- or post-conditioning regimen including immunosuppression is described. Methods: Un-mobilized, mononuclear cells were harvested from four patients with acquired aplastic anaemia by aphaeresis. Mononuclear cells of patients were cultured with purified monoclonal antibody against the monomorphic regions of the beta chain of MHC class II antigens (Clone CR3/43) for 3 h, to obtain autologous RHSC. Autologous RHSC were washed and infused into the four patients without the use of any pre- or post-conditioning regimen. Thereafter, the efficacy (engraftment) of autologous RHSC was assessed in these patients. Results: Following single infusion of the autologous RHSC, two of the four patients with aplastic anaemia become transfusion independent for more than seven years. Karyotyping and G-banding analysis prior and post-procedure in all patients remained the same. Interpretation & conclusions: The findings of this pilot study demonstrated the functional utility of reprogrammed fully differentiated adult cells into pluripotent stem cells with extensive repopulation potentials in a human setting and without any pre- or post-conditioning regimen, including immunosuppression. This autologous approach of stem cell creation may broaden the curative potentials of stem cell therapy to a wider

A novel autologous stem cell procedure for the treatment of aplastic anaemia using reprogrammed mature adult cells: a pilot study.

PubMed

Abuljadayel, Ilham Saleh; Mohanty, Dipika; Suri, Rajendar K

2012-06-01

Aplastic anaemia is a life threatening rare bone marrow failure disorder. The underlying haematopoietic cellular deficit leads to haemorrhage, infection and severe anaemia. The treatment of choice for this haematological condition is allogeneic bone marrow transplantation from fully matched HLA sibling. Though this procedure is curative in the majority of young patients with aplastic anaemia, extending this benefit to older patients or those lacking a family donor remains a major challenge. Herein, the safety and efficacy of infusing autologous retrodifferentiated haematopoietic stem cells (RHSC) into four patients with aplastic anaemia without the use of any pre- or post-conditioning regimen including immunosuppression is described. Un-mobilized, mononuclear cells were harvested from four patients with acquired aplastic anaemia by aphaeresis. Mononuclear cells of patients were cultured with purified monoclonal antibody against the monomorphic regions of the beta chain of MHC class II antigens (Clone CR3/43) for 3 h, to obtain autologous RHSC. Autologous RHSC were washed and infused into the four patients without the use of any pre- or post-conditioning regimen. Thereafter, the efficacy (engraftment) of autologous RHSC was assessed in these patients. Following single infusion of the autologous RHSC, two of the four patients with aplastic anaemia become transfusion independent for more than seven years. Karyotyping and G-banding analysis prior and post-procedure in all patients remained the same. The findings of this pilot study demonstrated the functional utility of reprogrammed fully differentiated adult cells into pluripotent stem cells with extensive repopulation potentials in a human setting and without any pre- or post-conditioning regimen, including immunosuppression. This autologous approach of stem cell creation may broaden the curative potentials of stem cell therapy to a wider population of patients with aplastic anaemia, including many patients suffering

Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis.

PubMed

Sheth, Ujash; Simunovic, Nicole; Klein, Guy; Fu, Freddie; Einhorn, Thomas A; Schemitsch, Emil; Ayeni, Olufemi R; Bhandari, Mohit

2012-02-15

The recent emergence of autologous blood concentrates, such as platelet-rich plasma, as a treatment option for patients with orthopaedic injuries has led to an extensive debate about their clinical benefit. We conducted a systematic review and meta-analysis to determine the efficacy of autologous blood concentrates in decreasing pain and improving healing and function in patients with orthopaedic bone and soft-tissue injuries. We searched MEDLINE and Embase for randomized controlled trials or prospective cohort studies that compared autologous blood concentrates with a control therapy in patients with an orthopaedic injury. We identified additional studies by searching through the bibliographies of eligible studies as well as the archives of orthopaedic conferences and meetings. Twenty-three randomized trials and ten prospective cohort studies were identified. There was a lack of consistency in outcome measures across all studies. In six randomized controlled trials (n = 358) and three prospective cohort studies (n = 88), the authors reported visual analog scale (VAS) scores when comparing platelet-rich plasma with a control therapy across injuries to the acromion, rotator cuff, lateral humeral epicondyle, anterior cruciate ligament, patella, tibia, and spine. The use of platelet-rich plasma provided no significant benefit up to (and including) twenty-four months across the randomized trials (standardized mean difference, -0.34; 95% confidence interval [CI], -0.75 to 0.06) or the prospective cohort studies (standardized mean difference, -0.20; 95% CI, -0.64 to 0.23). Both point estimates suggested a small trend favoring platelet-rich plasma, but the associated wide confidence intervals were consistent with nonsignificant effects. The current literature is complicated by a lack of standardization of study protocols, platelet-separation techniques, and outcome measures. As a result, there is uncertainty about the evidence to support the increasing clinical use of

Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome.

PubMed

Kim, Tae Beom; Shim, Young Sup; Lee, Sang Min; Son, Eun Suk; Shim, Jung Woo; Lee, Sang Pyo

2018-06-01

Post-orgasmic illness syndrome (POIS) is a very rare disease characterized by local allergic symptoms and transient flu-like illness that nearly always occur after masturbation, coitus, or spontaneous ejaculation and last for 2 to 7 days. In a previous case report, 2 patients with POIS received hyposensitization therapy composed of multiple subcutaneous injections of autologous semen that resulted in a gradual decrease of symptoms. However, this procedure requires patients to endure pain and discomfort during frequent subcutaneous injections and preceding masturbations to obtain the autologous semen used for therapy. Recent studies have suggested that intralymphatic immunotherapy is a promising new method of allergen-specific immunotherapy against allergic diseases, showing a faster onset and longer duration of therapeutic effects after only several intralymphatic injections. We report on a case of a Korean man with POIS who received intralymphatic immunotherapy that alleviated POIS-related symptoms and in whom the existence of semen-specific immunoglobulin E was confirmed using immunoglobulin E immunoblotting and enzyme-linked immunosorbent assay. Kim TB, Shim YS, Lee, SM, et al. Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome. Sex Med 2018;6:174-179. Copyright © 2018. Published by Elsevier Inc.

Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation.

PubMed

El-Jawahri, Areej; Chen, Yi-Bin; Brazauskas, Ruta; He, Naya; Lee, Stephanie J; Knight, Jennifer M; Majhail, Navneet; Buchbinder, David; Schears, Raquel M; Wirk, Baldeep M; Wood, William A; Ahmed, Ibrahim; Aljurf, Mahmoud; Szer, Jeff; Beattie, Sara M; Battiwalla, Minoo; Dandoy, Christopher; Diaz, Miguel-Angel; D'Souza, Anita; Freytes, Cesar O; Gajewski, James; Gergis, Usama; Hashmi, Shahrukh K; Jakubowski, Ann; Kamble, Rammurti T; Kindwall-Keller, Tamila; Lazarus, Hilard M; Malone, Adriana K; Marks, David I; Meehan, Kenneth; Savani, Bipin N; Olsson, Richard F; Rizzieri, David; Steinberg, Amir; Speckhart, Dawn; Szwajcer, David; Schoemans, Helene; Seo, Sachiko; Ustun, Celalettin; Atsuta, Yoshiko; Dalal, Jignesh; Sales-Bonfim, Carmem; Khera, Nandita; Hahn, Theresa; Saber, Wael

2017-05-15

To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post-transplantation. We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade 2-4 acute and chronic graft-versus-host disease (GVHD) in allogeneic HCT. The study included 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre-transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04-1.23; P = 0.004) and a higher incidence of grade 2-4 acute GVHD (HR, 1.25; 95% CI, 1.14-1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days-alive-and-out-of-the hospital (means ratio [MR] = 0.97; 95% CI, 0.95-0.99; P = 0.004). There were 512 (13.5%) patients with Pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98-1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97-0.99; P = 0.002). Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre

Impact of combined C1 esterase inhibitor/coagulation factor XIII or N-acetylcysteine/tirilazad mesylate administration on leucocyte adherence and cytokine release in experimental endotoxaemia.

PubMed

Birnbaum, J; Klotz, E; Spies, C D; Mueller, J; Vargas Hein, O; Feller, J; Lehmann, C

2008-01-01

We determined the effects of combinations of C1 esterase inhibitor (C1-INH) with factor XIII and of N-acetylcysteine (NAC) with tirilazad mesylate (TM) during lipo-polysaccharide (LPS)-induced endotoxaemia in rats. Forty Wistar rats were divided into four groups: the control (CON) group received no LPS; the LPS, C1-INH + factor XIII and NAC + TM groups received endotoxin infusions (5 mg/kg per h). After 30 min of endotoxaemia, 100 U/kg C1-INH + 50 U/kg factor XIII was administered to the C1-INH + factor XIII group, and 150 mg/kg NAC + 10 mg/kg TM was administered in the NAC + TM group. Administration of C1-INH + factor XIII and NAC + TM both resulted in reduced leucocyte adherence and reduced levels of interleukin-1beta (IL-1beta). The LPS-induced increase in IL-6 levels was amplified by both drug combinations. There was no significant effect on mesenteric plasma extravasation. In conclusion, the administration of C1-INH + factor XIII and NAC + TM reduced endothelial leucocyte adherence and IL-1beta plasma levels, but increased IL-6 levels.

Ophthalmic artery obstruction and cerebral infarction following periocular injection of autologous fat.

PubMed

Lee, Chang Mok; Hong, In Hwan; Park, Sung Pyo

2011-10-01

We report a case of ophthalmic artery obstruction combined with brain infarction following periocular autologous fat injection. The patient, a 44-year-old woman, visited our hospital for decreased visual acuity in her left eye and dysarthria one hour after receiving an autologous fat injection in the periocular area. Her best corrected visual acuity for the concerned eye was no light perception. Also, a relative afferent pupillary defect was detected in this eye. The left fundus exhibited widespread retinal whitening with visible emboli in several retinal arterioles. Diffusion-weighted magnetic resonance imaging of the brain showed a hyperintense lesion at the left insular cortex. Therefore, we diagnosed ophthalmic artery obstruction and left middle cerebral artery infarction due to fat emboli. The patient was managed with immediate ocular massage, carbon dioxide, and oxygen therapy. Following treatment, dysarthria improved considerably but there was no improvement in visual acuity.

Bothrops asper snake venom and its metalloproteinase BaP-1 activate the complement system. Role in leucocyte recruitment.

PubMed Central

Farsky, S H; Gonçalves, L R; Gutiérrez, J M; Correa, A P; Rucavado, A; Gasque, P; Tambourgi, D V

2000-01-01

The venom of the snake Bothrops asper, the most important poisonous snake in Central America, evokes an inflammatory response, the mechanisms of which are not well characterized. The objectives of this study were to investigate whether B. asper venom and its purified toxins--phospholipases and metalloproteinase--activate the complement system and the contribution of the effect on leucocyte recruitment. In vitro chemotaxis assays were performed using Boyden's chamber model to investigate the ability of serum incubated with venom and its purified toxins to induce neutrophil migration. The complement consumption by the venom was evaluated using an in vitro haemolytic assay. The importance of complement activation by the venom on neutrophil migration was investigated in vivo by injecting the venom into the peritoneal cavity of C5-deficient mice. Data obtained demonstrated that serum incubated with crude venom and its purified metalloproteinase BaP-1 are able to induce rat neutrophil chemotaxis, probably mediated by agent(s) derived from the complement system. This hypothesis was corroborated by the capacity of the venom to activate this system in vitro. The involvement of C5a in neutrophil chemotaxis induced by venom-activated serum was demonstrated by abolishing migration when neutrophils were pre-incubated with antirat C5a receptor antibody. The relevance of the complement system in in vivo leucocyte mobilization was further demonstrated by the drastic decrease of this response in C5-deficient mice. Pre-incubation of serum with the soluble human recombinant complement receptor type 1 (sCR 1) did not prevent the response induced by the venom, but abolished the migration evoked by metalloproteinase-activated serum. These data show the role of the complement system in bothropic envenomation and the participation of metalloproteinase in the effect. Also, they suggest that the venom may contain other component(s) which can cause direct activation of C5a. PMID:11200361

Insulin-secreting adipose-derived mesenchymal stromal cells with bone marrow-derived hematopoietic stem cells from autologous and allogenic sources for type 1 diabetes mellitus.

PubMed

Thakkar, Umang G; Trivedi, Hargovind L; Vanikar, Aruna V; Dave, Shruti D

2015-07-01

Stem cell therapy (SCT) is now the up-coming therapeutic modality for treatment of type 1 diabetes mellitus (T1DM). Our study was a prospective, open-labeled, two-armed trial for 10 T1DM patients in each arm of allogenic and autologous adipose-derived insulin-secreting mesenchymal stromal cells (IS-AD-MSC)+bone marrow-derived hematopoietic stem cell (BM-HSC) infusion. Group 1 received autologous SCT: nine male patients and one female patient; mean age, 20.2 years, disease duration 8.1 years; group 2 received allogenic SCT: six male patients and four female patients, mean age, 19.7 years and disease duration, 7.9 years. Glycosylated hemoglobin (HbA1c) was 10.99%; serum (S.) C-peptide, 0.22 ng/mL and insulin requirement, 63.9 IU/day in group 1; HbA1c was 11.93%, S.C-peptide, 0.028 ng/mL and insulin requirement, 57.55 IU/day in group 2. SCs were infused into the portal+thymic circulation and subcutaneous tissue under non-myelo-ablative conditioning. Patients were monitored for blood sugar, S.C-peptide, glutamic acid decarboxylase antibodies and HbA1c at 3-month intervals. Group 1 received mean SCs 103.14 mL with 2.65 ± 0.8 × 10(4) ISCs/kg body wt, CD34+ 0.81% and CD45-/90+/73+, 81.55%. Group 2 received mean SCs 95.33 mL with 2.07 ± 0.67 × 10(4) ISCs/kg body wt, CD34+ 0.32% and CD45-/90+/73+ 54.04%. No untoward effect was observed with sustained improvement in HbA1c and S.C-peptide in both groups with a decrease in glutamic acid decarboxylase antibodies and reduction in mean insulin requirement. SCT is a safe and viable treatment option for T1DM. Autologous IS-AD-MSC+ BM-HSC co-infusion offers better long-term control of hyperglycemia as compared with allogenic SCT. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Arthroscopic retrograde osteochondral autologous transplantation to chondral lesion in femoral head.

PubMed

Cetinkaya, Sarper; Toker, Berkin; Taser, Omer

2014-06-01

This report describes the treatment of 2 cases of full-thickness cartilage defect of the femoral head. The authors performed osteochondral autologous transplantation with a different technique that has not been reported to date. One patient was 37 years old, and the other was 42 years old. Both presented with hip pain. In both patients, radiograph and magnetic resonance imaging scan showed a focal chondral defect on the weight-bearing area of the femoral head and acetabular impingement. A retrograde osteochondral autologous transplantation technique combined with hip arthroscopy and arthroscopic impingement treatment was performed. After a 2-month recovery period, the symptoms were resolved. In the first year of follow-up, Harris Hip scores improved significantly (case 1, 56.6 to 87.6; case 2, 58.6 to 90). The technique described yielded good short- and midterm clinical and radiologic outcomes. To the authors' knowledge, this report is the first to describe a retrograde osteochondral transplantation technique performed with hip arthroscopy in the femoral head. Copyright 2014, SLACK Incorporated.

Retrograde tracing and toe spreading after experimental autologous nerve transplantation and crush injury of the sciatic nerve: a descriptive methodological study.

PubMed

van Neerven, Sabien Ga; Bozkurt, Ahmet; O'Dey, Dan Mon; Scheffel, Juliane; Boecker, Arne H; Stromps, Jan-Philipp; Dunda, Sebastian; Brook, Gary A; Pallua, Norbert

2012-04-30

Evaluation of functional and structural recovery after peripheral nerve injury is crucial to determine the therapeutic effect of a nerve repair strategy. In the present study, we examined the relationship between the structural evaluation of regeneration by means of retrograde tracing and the functional analysis of toe spreading. Two standardized rat sciatic nerve injury models were used to address this relationship. As such, animals received either a 2 cm sciatic nerve defect (neurotmesis) followed by autologous nerve transplantation (ANT animals) or a crush injury with spontaneous recovery (axonotmesis; CI animals). Functional recovery of toe spreading was observed over an observation period of 84 days. In contrast to CI animals, ANT animals did not reach pre-surgical levels of toe spreading. After the observation period, the lipophilic dye DiI was applied to label sensory and motor neurons in dorsal root ganglia (DRG; sensory neurons) and spinal cord (motor neurons), respectively. No statistical difference in motor or sensory neuron counts could be detected between ANT and CI animals.In the present study we could indicate that there was no direct relationship between functional recovery (toe spreading) measured by SSI and the number of labelled (motor and sensory) neurons evaluated by retrograde tracing. The present findings demonstrate that a multimodal approach with a variety of independent evaluation tools is essential to understand and estimate the therapeutic benefit of a nerve repair strategy.

Long term results in refractory tennis elbow using autologous blood.

PubMed

Gani, Naseem Ul; Khan, Hayat Ahmad; Kamal, Younis; Farooq, Munir; Jeelani, Hina; Shah, Adil Bashir

2014-10-27

Tennis elbow (TE) is one of the commonest myotendinosis. Different treatment options are available and autologous blood injection has emerged as the one of the acceptable modalities of treatment. Long term studies over a larger group of patients are however lacking. The purpose of this study was to evaluate these patients on longer durations. One-hundred and twenty patients of TE, who failed to respond to conventional treatment including local steroid injections were taken up for this prospective study over the period from year 2005 to 2011 and were followed up for the minimum of 3 years (range 3-9 years). Two mL of autologous blood was taken from the ipsilateral limb and injected into the lateral epicondyle. The effectiveness of the procedure was assessed by Pain Rating Sscale and Nirschl Staging, which was monitored before the procedure, at first week, monthly for first three months, at 6 months and then 3 monthly for first year, six monthly for next 2 years and then yearly. Statistical analysis was done and a P value of <0.05 was taken as significant. The patients (76 females and 44 males) were evaluated after procedure. The mean age group was 40.67±8.21. The mean follow up was 5.7±1.72 (range 3 to 9 years). The mean pain score and Nirschl stage before the procedure was 3.3±0.9 and 6.2±0.82 respectively. At final follow up the pain score and Nirschl were 1.1±0.9 and 1.5±0.91 respectively. Autologous blood injection was found to be one of the modalities for treatment of TE. Being cheap, available and easy method of treatment, it should be considered as a treatment modality before opting for the surgery. Universal guidelines for the management of tennis elbow should be made as there is lot of controversy regarding the treatment.

Identification, characterization and leucocyte expression of Siglec-10, a novel human sialic acid-binding receptor.

PubMed Central

Munday, J; Kerr, S; Ni, J; Cornish, A L; Zhang, J Q; Nicoll, G; Floyd, H; Mattei, M G; Moore, P; Liu, D; Crocker, P R

2001-01-01

Here we characterize Siglec-10 as a new member of the Siglec family of sialic acid-binding Ig-like lectins. A full-length cDNA was isolated from a human spleen library and the corresponding gene identified. Siglec-10 is predicted to contain five extracellular Ig-like domains and a cytoplasmic tail containing three putative tyrosine-based signalling motifs. Siglec-10 exhibited a high degree of sequence similarity to CD33-related Siglecs and mapped to the same region, on chromosome 19q13.3. The expressed protein was able to mediate sialic acid-dependent binding to human erythrocytes and soluble sialoglycoconjugates. Using specific antibodies, Siglec-10 was detected on subsets of human leucocytes including eosinophils, monocytes and a minor population of natural killer-like cells. The molecular properties and expression pattern suggest that Siglec-10 may function as an inhibitory receptor within the innate immune system. PMID:11284738

Débridement and Autologous Lipotransfer for Chronic Ulceration of the Diabetic Foot and Lower Limb Improves Wound Healing.

PubMed

Stasch, Tilman; Hoehne, Julius; Huynh, Tuan; De Baerdemaeker, Randy; Grandel, Siegfried; Herold, Christian

2015-12-01

The application of autologous lipotransfer (fat grafting, lipofilling) in reconstructive surgery is steadily becoming more popular as evidence of the regenerative and reparative effects of fat becomes better known. The authors investigated the use of autologous lipotransfer for treatment of chronic diabetic and other foot and lower limb ulcers. Twenty-six patients with nonhealing wounds were treated with surgical débridement and autologous lipotransfer (using the débridement and autologous lipotransfer method). The mean age of the wounds before intervention was 16.7 months. Wound size after débridement averaged 5.1 ± 2.6 cm2. On average, 7.1 ± 3.3 cc of lipoaspirate was transferred into the wound area. Twenty-two of 25 wounds (88 percent) healed completely within a mean of 68.0 ± 33.0 days. A reduction of wound size by 50 percent was achieved after an average of 4 weeks. In one patient with an ulcer within particularly scarred tissues on the lower limb, a repeated session of lipotransfer led to complete wound healing after another 4 weeks. The authors describe a simple and useful technique to improve wound healing in diabetic feet and chronic lower limb ulcers with a background of peripheral vascular disease, where other interventional options to achieve wound healing have failed.

A population-based cohort study of late mortality in adult autologous hematopoietic stem cell transplant recipients in Australia.

PubMed

Ashton, Lesley J; Le Marsney, Renate E; Dodds, Anthony J; Nivison-Smith, Ian; Wilcox, Leonie; O'Brien, Tracey A; Vajdic, Claire M

2014-07-01

We assessed overall and cause-specific mortality and risk factors for late mortality in a nation-wide population-based cohort of 4547 adult cancer patients who survived 2 or more years after receiving an autologous hematopoietic stem cell transplantation (HSCT) in Australia between 1992 and 2005. Deaths after HSCT were identified from the Australasian Bone Marrow Transplant Recipient Registry and through data linkage with the National Death Index. Overall, the survival probability was 56% at 10 years from HSCT, ranging from 34% for patients with multiple myeloma to 90% for patients with testicular cancer. Mortality rates moved closer to rates observed in the age- and sex-matched Australian general population over time but remained significantly increased 11 or more years from HSCT (standardized mortality ratio, 5.9). Although the proportion of deaths from nonrelapse causes increased over time, relapse remained the most frequent cause of death for all diagnoses, 10 or more years after autologous HSCT. Our findings show that prevention of disease recurrence remains 1 of the greatest challenges for autologous HSCT recipients, while the increasing rates of nonrelapse deaths due to the emergence of second cancers, circulatory diseases, and respiratory diseases highlight the long-term health issues faced by adult survivors of autologous HSCT. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Allogeneic versus autologous derived cell sources for use in engineered bone-ligament-bone grafts in sheep anterior cruciate ligament repair.

PubMed

Mahalingam, Vasudevan D; Behbahani-Nejad, Nilofar; Horine, Storm V; Olsen, Tyler J; Smietana, Michael J; Wojtys, Edward M; Wellik, Deneen M; Arruda, Ellen M; Larkin, Lisa M

2015-03-01

The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use.

Safety and efficacy of cryopreserved autologous platelet concentrates in HLA-alloimmunized patients with hematologic malignancies.

PubMed

Gerber, Bernhard; Alberio, Lorenzo; Rochat, Sophie; Stenner, Frank; Manz, Markus G; Buser, Andy; Schanz, Urs; Stussi, Georg

2016-10-01

Curative chemotherapy approaches in patients with malignancies and platelet (PLT) transfusion refractoriness due to alloimmunization may be hampered by the lack of suitable PLT donors. For these patients, transfusion of cryopreserved autologous PLTs is an option, but is time- and resource-consuming. We aimed at further simplifying this process. A retrospective single-center analysis was conducted on the transfusion of cryopreserved autologous PLTs in nine female alloimmunized, PLT transfusion-refractory patients treated for acute leukemia (n = 8) and non-Hodgkin's lymphoma (n = 1). No additional processing was used before transfusion, and most notably, washing and centrifugation steps were omitted. Clinical efficacy and safety, as well as a flow cytometric assessment of structural and functional PLT changes, were analyzed. A total of 40 autologous PLT concentrates were thawed at bedside and transfused a median of 32 (range, 9 to 994) days after cryopreservation. No major bleeds and no severe dimethyl sulfoxide toxicity were observed. The median PLT count increments did not differ 1 and 18 to 24 hours after transfusion and reached 6 × 10 9 /L (interquartile range [IQR], 3 × 10 9 -7.5 × 10 9 /L) and 6 × 10 9 /L (IQR, 2.5 × 10 9 -9.5 × 10 9 /L), respectively. Cryopreservation resulted in partial activation of one-third of the PLTs. In vitro stimulation with strong agonists induced additional full activation of cryopreserved PLTs: median, 55% (IQR, 42%-60%) after thrombin and 39% (IQR, 36%-39%) after convulxin. The transfusion of cryopreserved autologous PLTs is feasible and safe. Despite the cryopreservation process, PLT functionality is partially maintained. © 2016 AABB.

The Impact of pre-transplant depression on the outcomes of allogeneic and autologous hematopoietic stem cell transplantation

PubMed Central

El-Jawahri, Areej; Chen, Yi-Bin; Brazauskas, Ruta; He, Naya; Lee, Stephanie J.; Knight, Jennifer; Majhail, Navneet; Buchbinder, David; Schears, Raquel M.; Wirk, Baldeep M.; Wood, William A.; Ahmed, Ibrahim; Aljurf, Mahmoud; Szer, Jeff; Beattie, Sara M.; Battiwalla, Minoo; Dandoy, Christopher; Diaz, Miguel-Angel; D’Souza, Anita; Freytes, Cesar O.; Gajewski, James; Gergis, Usama; Hashmi, Shahrukh K.; Jakubowski, Ann; Kamble, Rammurti T.; Kindwall-Keller, Tamila; Lazarus, Hilard M.; Malone, Adriana K.; Marks, David I.; Meehan, Kenneth; Savani, Bipin N.; Olsson, Richard F.; Rizzieri, David; Steinberg, Amir; Speckhart, Dawn; Szwajcer, David; Schoemans, Helene; Seo, Sachiko; Ustun, Celalettin; Atsuta, Yoshiko; Dalal, Jignesh; Sales-Bonfim, Carmem; Khera, Nandita; Hahn, Theresa; Saber, Wael

2017-01-01

Background To evaluate the impact of depression prior to autologous and allogeneic HCT on clinical outcomes post-transplant. Methods We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n=3786) or allogeneic (n=7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment vs. those without pre-HCT depression. Using Cox regression models, we compared OS between patients with or without depression. We compared the number of days-alive-and-out-of-the-hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade II-IV acute and chronic GVHD in allogeneic HCT. Results 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression underwent allogeneic HCT in 2008-2012 were included. Pre-transplant depression was associated with lower OS (HR=1.13, 95%CI1.04-1.23, P=0.004) and higher incidence of grade II-IV acute GVHD (HR=1.25, 95%CI 1.14-1.37, P<0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days alive and out-of-the hospital (Means-Ratio (MR)=0.97, 95%CI0.95-0.99, P=0.004). There were 512 (13.5%) patients with pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR=1.15, 95%CI0.98-1.34, P=0.096), but was associated with fewer days-alive-and-out-of-the-hospital (MR=0.98, 95%CI0.97-0.99, P=0.002). Conclusions Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients, and fewer days-alive-and-out-of-the-hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre-transplant depression represent a vulnerable population at risk for post-transplant complications. PMID:28102896

A Clinical Study of Autologous Bone Marrow Mononuclear Cells for Cerebral Palsy Patients: A New Frontier

PubMed Central

Sharma, Alok; Sane, Hemangi; Gokulchandran, Nandini; Kulkarni, Pooja; Sundaram, Jyothi; Paranjape, Amruta; Shetty, Akshata; Bhagwanani, Khushboo; Biju, Hema; Badhe, Prerna

2015-01-01

Cerebral palsy is a nonprogressive heterogeneous group of neurological disorders with a growing rate of prevalence. Recently, cellular therapy is emerging as a potential novel treatment strategy for cerebral palsy. The various mechanisms by which cellular therapy works include neuroprotection, immunomodulation, neurorestoration, and neurogenesis. We conducted an open label, nonrandomized study on 40 cases of cerebral palsy with an aim of evaluating the benefit of cellular therapy in combination with rehabilitation. These cases were administered autologous bone marrow mononuclear cells intrathecally. The follow-up was carried out at 1 week, 3 months, and 6 months after the intervention. Adverse events of the treatment were also monitored in this duration. Overall, at six months, 95% of patients showed improvements. The study population was further divided into diplegic, quadriplegic, and miscellaneous group of cerebral palsy. On statistical analysis, a significant association was established between the symptomatic improvements and cell therapy in diplegic and quadriplegic cerebral palsy. PET-CT scan done in 6 patients showed metabolic improvements in areas of the brain correlating to clinical improvements. The results of this study demonstrate that cellular therapy may accelerate the development, reduce disability, and improve the quality of life of patients with cerebral palsy. PMID:25788947

Patients referred to an indoor air health clinic: exposure to water-damaged buildings causes an increase of lymphocytes in bronchoalveolar lavage and a decrease of CD19 leucocytes in peripheral blood.

PubMed

Wolff, Henrik; Mussalo-Rauhamaa, Helena; Raitio, Hanna; Elg, Peter; Orpana, Arto; Piilonen, Anneli; Haahtela, Tari

2009-01-01

Respiratory and other symptoms are often associated with exposure to microbes present in water-damaged buildings. We examined 82 consecutive patients referred to the Indoor Air Clinic, Helsinki University Hospital, due to symptoms suspected of having been caused by long-term exposure to water damage in the home or workplace. Exposure to water damage was assessed by building inspections and microbial analyses as needed. Bronchoalveolar lavage, lung function measurements, skin prick tests to inhalant allergens and radiological examinations were performed in all patients. Leucocyte subsets in peripheral blood were analysed in 35 patients. Marked water damage was detected in the homes or workplaces of 47 (59%) patients; the remaining 34 patients formed the control group. The exposed group expressed more symptoms in total than the control group: fatigue, conjunctival symptoms, rhinitis with sinusitis, recurrent bronchitis and asthma were more common in the exposed group, but a significant difference was seen only for headache. In BAL (bronchoalveolar lavage) samples, lymphocytes represented 25% of the total cell population in non-smoking-exposed patients compared with 12% in control patients (p=0.004). In peripheral blood, CD19 leucocytes were significantly decreased in the exposed group (7.5% versus 12.3%; p<0.01). Confirmed exposure to water damage was associated with an increase in symptoms. Exposure to water damage caused a significant change in the cellular composition in BAL fluid (lymphocytosis) and blood (decrease of CD19 cells). The depletion of CD19 leucocytes in peripheral blood may indicate an active immune response in the lungs.

Development of an autologous canine cancer vaccine system for resectable malignant tumors in dogs.

PubMed

Yannelli, J R; Wouda, R; Masterson, T J; Avdiushko, M G; Cohen, D A

2016-12-01

While conventional therapies exist for canine cancer, immunotherapies need to be further explored and applied to the canine setting. We have developed an autologous cancer vaccine (K9-ACV), which is available for all dogs with resectable disease. K9-ACV was evaluated for safety and immunogenicity for a variety of cancer types in a cohort of companion dogs under veterinary care. The autologous vaccine was prepared by enzymatic digestion of solid tumor biopsies. The resultant single cell suspensions were then UV-irradiated resulting in immunogenic cell death of the tumor cells. Following sterility and endotoxin testing, the tumor cells were admixed with CpG ODN adjuvant and shipped to the participating veterinary clinics. The treating veterinarians then vaccinated each patient with three intradermal injections (10 million cells per dose) at 30-day intervals (one prime and two boost injections). In a cohort of 20 dogs completing the study, 17 dogs (85%) developed an augmented IgG response to autologous tumor antigens as demonstrated using western blot analysis of pre- and post-peripheral blood samples. We also report several dogs have lived beyond expected survival time based on previously published data. In summary, K9-ACV is an additional option to be considered for the treatment of dogs with resectable cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

From fresh heterologous oocyte donation to autologous oocyte banking.

PubMed

Stoop, D

2012-01-01

Today, oocyte donation has become well established, giving rise to thousands of children born worldwide annually. The introduction of oocyte cryopreservation through vitrification allows the introduction of egg banking, improving the efficiency and comfort of oocyte donation. Moreover, the vitrification technique can now enable autologous donation of oocytes to prevent future infertility. We evaluated fresh heterologous oocyte donation in terms of obstetrical and perinatal outcome as well as of the reproductive outcome of past donors. We then evaluated the efficiency of a closed vitrification device and its clinical applications within ART. Thirdly, we evaluated the opinion of women with regard to preventive egg freezing and the efficiency of a human oocyte in relation to age. Oocyte donation is associated with an increased risk of first trimester bleeding and pregnancy induced hypertension. Donating oocytes does not seem to increase the likelihood for a later need of fertility treatment. The chance of an oocyte to result in live birth (utilization rate) in women <37 years old remains constant with a mean of 4.47%. A significant proportion of young women would consider safeguarding their reproductive potential through egg freezing or are at least open to the idea. The introduction of efficient oocyte cryopreservation has revolutionized oocyte donation through the establishment of eggbank donation. The technique also enables women to perform autologous donation after preventive oocyte storage in order to circumvent their biological clock.

Effective regeneration of dystrophic muscle using autologous iPSC-derived progenitors with CRISPR-Cas9 mediated precise correction.

PubMed

Hagan, Mackenzie; Ashraf, Muhammad; Kim, Il-Man; Weintraub, Neal L; Tang, Yaoliang

2018-01-01

Duchenne muscular dystrophy (DMD) is a lethal muscle wasting disease caused by a lack of dystrophin, which eventually leads to apoptosis of muscle cells and impaired muscle contractility. Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9) gene editing of induced pluripotent stem cells (IPSC) offers the potential to correct the DMD gene defect and create healthy IPSC for autologous cell transplantation without causing immune activation. However, IPSC carry a risk of tumor formation, which can potentially be mitigated by differentiation of IPSC into myogenic progenitor cells (MPC). We hypothesize that precise genetic editing in IPSC using CRISPR-Cas9 technology, coupled with MPC differentiation and autologous transplantation, can lead to safe and effective muscle repair. With future research, our hypothesis may provide an optimal autologous stem cell-based approach to treat the dystrophic pathology and improve the quality of life for patients with DMD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Office-Based Autologous Fat Injection Laryngoplasty for Glottic Insufficiency in Patients Under 50 Years Old.

PubMed

Hu, Hao-Chun; Hung, Yi-Ting; Lin, Shu-Yi; Tung, Tao-Hsin; Chang, Shyue-Yih

2018-04-17

We sought to determine the outcomes of office-based autologous fat injection laryngoplasty in the treatment of patients under 50 years old with glottic insufficiency but without neurological problems or acquired organic lesions in the vocal fold. We conducted a retrospective chart review of consecutive patients under 50 years of age who underwent office-based autologous fat injection laryngoplasty for glottic insufficiency. None of the patients presented neurological problems or acquired organic lesions in the vocal fold. Videolaryngostroboscopic data, objective voice assessment, perceptual measurements of vocal quality, and subjective ratings of voice quality were evaluated before and after treatment. The 23 patients (7 men and 16 women) in this study presented significant improvements in phonatory function in terms of maximum phonation time, jitter, grade, asthenia, and Voice Handicap Index-10 (VHI-10) values at 3 months. Significant improvements in terms of jitter, noise-to-harmonic ratio, grade, roughness, breathiness, asthenia, and the VHI-10 values were also observed at 6 months. Glottic insufficiency in younger patients without neurological problems or acquired organic lesions in the vocal fold can be treated effectively using office-based autologous fat injection laryngoplasty. Significant improvements in phonatory function were observed even 6 months after surgery. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Postmastectomy Breast Reconstruction With the Totally Autologous Latissimus Dorsi Flap in the Thin, Small-Breasted Woman: Give It More Thought!

PubMed

Kazzazi, Fawz; Ching, Rosanna C; Malata, Charles M

2018-01-01

Introduction: Thin women have fewer autologous tissue breast reconstructive options than their higher body mass index counterparts-due to a lack of adequate donor sites. They are therefore usually offered expander/implant techniques. The total autologous latissimus dorsi flap is generally used in "well-padded" individuals, as they have enough fat on their back on which a completely autologous reconstruction could be based. When implant-based reconstruction is contraindicated (for instance due to planned adjuvant radiotherapy) or unacceptable to the patient, the total autologous latissimus dorsi flap can provide adequate tissue volume by utilizing the additional back fat deposits even in the thin, small-breasted patient. This option is often overlooked by many surgeons. Our case series assesses indications and patient and surgeon satisfaction with the cosmetic outcome of this technique. Methods: The oncological and clinical details of 6 patients with breast cancer who underwent total autologous latissimus dorsi myocutaneous flap immediate breast reconstruction by a single surgeon over an 8-year period were reviewed. An objective assessment of satisfaction with the cosmetic result was made by whether any additional surgical interventions (ipsilateral fat grafting/implant augmentation or contralateral liposuction/ reduction) were needed or not. A subjective assessment of breast symmetry by the surgeon using photographic records was also undertaken. The aesthetic outcomes were also objectively quantified using the BCCT.core software, initially developed for assessing the results of breast conservation surgery. Results: All 6 patients had small breasts and a low or normal body mass index. The mastectomies were performed for invasive carcinoma (n = 3) and extensive high-grade ductal carcinoma in situ (n = 3). Four had axillary surgery (2 sentinel lymph node biopsies and 2 axillary clearances), and 3 received adjuvant radiotherapy. All were happy with their reconstructive

Postmastectomy Breast Reconstruction With the Totally Autologous Latissimus Dorsi Flap in the Thin, Small-Breasted Woman: Give It More Thought!

PubMed Central

Kazzazi, Fawz; Ching, Rosanna C.; Malata, Charles M.

2018-01-01

Introduction: Thin women have fewer autologous tissue breast reconstructive options than their higher body mass index counterparts—due to a lack of adequate donor sites. They are therefore usually offered expander/implant techniques. The total autologous latissimus dorsi flap is generally used in “well-padded” individuals, as they have enough fat on their back on which a completely autologous reconstruction could be based. When implant-based reconstruction is contraindicated (for instance due to planned adjuvant radiotherapy) or unacceptable to the patient, the total autologous latissimus dorsi flap can provide adequate tissue volume by utilizing the additional back fat deposits even in the thin, small-breasted patient. This option is often overlooked by many surgeons. Our case series assesses indications and patient and surgeon satisfaction with the cosmetic outcome of this technique. Methods: The oncological and clinical details of 6 patients with breast cancer who underwent total autologous latissimus dorsi myocutaneous flap immediate breast reconstruction by a single surgeon over an 8-year period were reviewed. An objective assessment of satisfaction with the cosmetic result was made by whether any additional surgical interventions (ipsilateral fat grafting/implant augmentation or contralateral liposuction/ reduction) were needed or not. A subjective assessment of breast symmetry by the surgeon using photographic records was also undertaken. The aesthetic outcomes were also objectively quantified using the BCCT.core software, initially developed for assessing the results of breast conservation surgery. Results: All 6 patients had small breasts and a low or normal body mass index. The mastectomies were performed for invasive carcinoma (n = 3) and extensive high-grade ductal carcinoma in situ (n = 3). Four had axillary surgery (2 sentinel lymph node biopsies and 2 axillary clearances), and 3 received adjuvant radiotherapy. All were happy with their

Treatment of chronic non-healing ulcers using autologous platelet rich plasma: a case series.

PubMed

Suthar, Manish; Gupta, Saniya; Bukhari, Suhail; Ponemone, Venkatesh

2017-02-27

Non-healing ulcers are a major health problem worldwide and have great impact at personal, professional and social levels, with high cost in terms of human and material resources. Recalcitrant non-healing ulcers are inevitable and detrimental to the lower limb and are a major cause of non-traumatic lower limb amputations. Application of autologous Platelet Rich Plasma (PRP) has been a major breakthrough for the treatment of non-healing and diabetic foot ulcers, as it is an easy and cost-effective method, and provides the necessary growth factors that enhance tissue healing. PRP is a conglomeration of thrombocytes, cytokines and various growth factors which are secreted by α-granules of platelets that augment the rate of natural healing process with decrease in time. The purpose of this case series was to evaluate the safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers on the lower extremity. Autologous PRP was prepared from whole blood utilizing a rapid, intraoperative point-of-care system that works on the principle of density gradient centrifugation. Twenty Four (24) patients with non-healing ulcers of different etiologies, who met the inclusion criteria, were treated with single dose of subcutaneous PRP injections along with topical application of PRP gel under compassionate use. The mean age of the treated patients was 62.5 ± 13.53 years and they were followed-up for a period of 24 weeks. All the patients showed signs of wound healing with reduction in wound size, and the mean time duration to ulcer healing was 8.2 weeks. Also, an average five fold increase in the platelet concentrate was observed in the final PRP product obtained using the rapid point-of-care device, and the average platelet dose administered to the patients was 70.10 × 10 8 . This case series has demonstrated the potential safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers. NCT

Autologous Platelet Concentrates as Treatment for Avascular Necrosis of Femoral Head in a Dog.

PubMed

Parra, Estefanía; Vergara, Andrea; Silva, Raúl F

2017-03-01

Avascular necrosis of the femoral head is a developmental disturbance that generally affects young dogs of small breeds and produces ischemic necrosis of the femoral head resulting in an incongruous and malformed joint. The most common treatment is the excisional arthroplasty of the head and femoral neck. The aim of this study is to describe the treatment of avascular necrosis in a Yorkshire dog using intra-articular injections of autologous platelet concentrate. Evaluations were made at 0, 15, 30, 60, and 120 days of treatment, describing the following parameters: clinical gait analysis, perimetry, goniometry, and radiographic evaluations. The results obtained in this case suggest that the autologous platelet concentrate may be an alternative for the treatment of avascular necrosis of the femoral head in dogs. Copyright © 2017 Elsevier Inc. All rights reserved.

Markers of endothelial dysfunction and leucocyte activation in Saudi and non-Saudi haplotypes of sickle cell disease.

PubMed

Al Najjar, Salwa; Adam, Soheir; Ahmed, Nessar; Qari, Mohamed

2017-01-01

Sickle cell disease (SCD) is an autosomal recessive inherited hemoglobinopathy, characterized by chronic hemolysis and recurrent vaso-occlusive crisis (VOC). This study investigates changes in leucocyte subsets and the relationship between cell adhesion molecule expression and disease manifestations in patients during steady state and acute VOC. We compared soluble E-selectin and P-selectin levels in 84 SCD patients, in steady state and during VOC to 84 healthy controls. Using immunophenotyping, we also compared lymphocyte subsets in these three groups. Further, we compared E-selectin and P-selectin levels in patients of Saudi ethnicity to non-Saudi patients, in all three groups. Lymphocyte subsets showed high percentages of total T lymphocytes, T helper and suppressor lymphocytes, B lymphocytes as well as NK cells in patients with SCD during steady state, while B lymphocytes and NK cells were significantly higher during acute VOC crisis. High levels of both soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) markers were demonstrated in the serum of patients with SCD during both steady state and acute VOC. Levels of selectins were significantly higher in acute VOC. The immunophenotypic expression of L-selectin, on leucocytes, was high in SCD both during steady state and during acute VOC in comparison to normal control subjects. There was no significant difference in all three study groups between Saudi and non-Saudi patients. These findings suggest that patients with SCD have increased expression of adhesion molecules: E-selectin and P-selectin, which play an important role in the pathogenesis of VOC. Despite the distinct phenotype of Saudi patients with SCD, there was no significant difference in levels of soluble E-selectin and soluble P-selectin between Saudi and non-Saudi patients in all three groups. While sickle cell disease is a well-recognized state of chronic inflammation, the role of specific adhesion molecules is steadily unraveling

High acceptance rate of hybrid allogeneic-autologous umbilical cord blood banking among actual and potential Swiss donors.

PubMed

Wagner, Anna-Margaretha; Krenger, Werner; Suter, Eva; Ben Hassem, Dorra; Surbek, Daniel V

2013-07-01

Two competitive concepts of umbilical cord blood (UCB) banking are currently available: either allogeneic UCB is donated to a public bank or autologous cells are stored in a private bank. Allogeneic-autologous hybrid banking is a new concept that combines these two approaches. However, acceptance of hybrid UCB banking among potential donors is unknown to date. In a prospective survey, we aimed to establish the acceptance of the hybrid banking model among actual and potential UCB donors in Switzerland. The study groups consisted of parents and pregnant women with or without children. As control group, women at reproductive ages were investigated. The majority of participants agreed fundamentally with UCB donation, and overall acceptance of private banking was 47%. If a possibility for hybrid banking were to be made available, 49% would opt for such a public-private model and only 13% would choose private banking alone. Among the proponents of hybrid banking, a majority of participants chose donor cell splitting over the sequential banking mode. Fifty-six percent of responders wished prior notification before the release of their donated UCB to a foreign recipient. This is the first study which compared the acceptance of allogeneic, autologous, and hybrid allogeneic-autologous UCB banking in different target groups. We demonstrated that hybrid cord blood banking is the preferred model of banking among actual and potential UCB donors. With increasing demand for UCB in the future, health care providers should therefore consider offering hybrid banking as a viable storage option. © 2012 American Association of Blood Banks.

Management of Contaminated Autologous Grafts in Plastic Surgery

PubMed Central

Centeno, Robert F; Desai, Ankit R; Watson, Marla E

2008-01-01

Background: Contamination of autologous grafts unfortunately occurs in plastic surgery, but the literature provides no guidance for management of such incidents. Methods: American Society of Aesthetic Plastic Surgery members were asked to complete an online survey that asked about the number and causes of graft contaminations experienced, how surgeons dealt with the problem, the clinical outcomes, and patient disclosure. Results: Nineteen hundred surgeons were asked to participate in the survey, and 223 responded. Of these, 70% had experienced at least 1 graft contamination incident, with 26% experiencing 4 or more. The most frequently reported reason for graft contamination was a graft falling on the floor (reported by 75%). Nearly two thirds of the contaminated grafts related to craniofacial procedures. Ninety-four percent of grafts were managed with decontamination and completion of the operation. The most common method of decontamination was washing with povidone-iodine, but this practice is contrary to recommendations in the literature. Only 3 surgeons (1.9%) said a clinical infection developed following decontaminated graft use. Patients were not informed in 60% of graft contamination incidents. The survey results and review of the literature led to development of algorithms for the management of inadvertent graft contamination and patient disclosure. Conclusions: Although autologous grafts do become contaminated in plastic surgery, the overwhelming majority can be safely decontaminated and produce minimal or no clinical sequelae. The algorithms presented are intended to serve as guides for prevention of contamination events or for their management should they occur. PMID:18496583

Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

DTIC Science & Technology

2016-07-01

AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Stem Cells To Improve...5b. GRANT NUMBER W81XWH-15-2-0026 CClinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Stem Cells To Improve...co- treatments of a commercially available decellularized processed peripheral nerve allograft scaffold (Avance® Nerve Graft, AxoGen, Alachua FL) with

Using corneal confocal microscopy to track changes in the corneal layers of dry eye patients after autologous serum treatment.

PubMed

Mahelkova, Gabriela; Jirsova, Katerina; Seidler Stangova, Petra; Palos, Michalis; Vesela, Viera; Fales, Ivan; Jiraskova, Nada; Dotrelova, Dagmar

2017-05-01

In vivo corneal confocal microscopy allows the examination of each layer of the cornea in detail and the identification of pathological changes at the cellular level. The purpose of this study was to identify the possible effects of a three-month treatment with autologous serum eye-drops in different corneal layers of patients with severe dry eye disease using corneal confocal microscopy. Twenty-six patients with dry eye disease were included in the study. Corneal fluorescein staining was performed. The corneas of the right eyes were examined using in vivo corneal confocal microscopy before and after a three-month treatment with autologous serum drops. The densities of superficial and basal epithelial cells, Langerhans cells, the keratocytes and activated keratocytes, the density of endothelial cells and the status of the sub-basal nerve plexus fibres were evaluated. A significant decrease in corneal fluorescein staining was found after the three-month autologous serum treatment (p = 0.0006). The basal epithelial cell density decreased significantly (p = 0.001), while the density of superficial epithelial cells did not change significantly (p = 0.473) nor did the number of Langerhans cells or activated keratocytes (p = 0.223; p = 0.307, respectively). There were no differences in the other corneal cell layers or in the status of the nerve fibres. The results demonstrate the ability of corneal confocal microscopy to evaluate an improvement in the basal epithelial cell layer of the cornea after autologous serum treatment in patients with dry eye disease. More studies with longer follow-up periods are needed to elucidate the suitability of corneal confocal microscopy to follow the effect of autologous serum treatment on nerve fibres or other corneal layers in dry eye disease patients. © 2016 Optometry Australia.

Repair of Torn Avascular Meniscal Cartilage Using Undifferentiated Autologous Mesenchymal Stem Cells: From In Vitro Optimization to a First-in-Human Study.

PubMed

Whitehouse, Michael R; Howells, Nicholas R; Parry, Michael C; Austin, Eric; Kafienah, Wael; Brady, Kyla; Goodship, Allen E; Eldridge, Jonathan D; Blom, Ashley W; Hollander, Anthony P

2017-04-01

Meniscal cartilage tears are common and predispose to osteoarthritis (OA). Most occur in the avascular portion of the meniscus where current repair techniques usually fail. We described previously the use of undifferentiated autologous mesenchymal stem cells (MSCs) seeded onto a collagen scaffold (MSC/collagen-scaffold) to integrate meniscal tissues in vitro. Our objective was to translate this method into a cell therapy for patients with torn meniscus, with the long-term goal of delaying or preventing the onset of OA. After in vitro optimization, we tested an ovine-MSC/collagen-scaffold in a sheep meniscal cartilage tear model with promising results after 13 weeks, although repair was not sustained over 6 months. We then conducted a single center, prospective, open-label first-in-human safety study of patients with an avascular meniscal tear. Autologous MSCs were isolated from an iliac crest bone marrow biopsy, expanded and seeded into the collagen scaffold. The resulting human-MSC/collagen-scaffold implant was placed into the meniscal tear prior to repair with vertical mattress sutures and the patients were followed for 2 years. Five patients were treated and there was significant clinical improvement on repeated measures analysis. Three were asymptomatic at 24 months with no magnetic resonance imaging evidence of recurrent tear and clinical improvement in knee function scores. Two required subsequent meniscectomy due to retear or nonhealing of the meniscal tear at approximately 15 months after implantation. No other adverse events occurred. We conclude that undifferentiated MSCs could provide a safe way to augment avascular meniscal repair in some patients. Registration: EU Clinical Trials Register, 2010-024162-22. Stem Cells Translational Medicine 2017;6:1237-1248. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Cellular Therapy With Human Autologous Adipose-Derived Adult Stem Cells for Advanced Keratoconus.

PubMed

Alió Del Barrio, Jorge L; El Zarif, Mona; de Miguel, María P; Azaar, Albert; Makdissy, Norman; Harb, Walid; El Achkar, Ibrahim; Arnalich-Montiel, Francisco; Alió, Jorge L

2017-08-01

The aim of this phase 1 study was to preliminarily evaluate the safety and efficacy of autologous adipose-derived adult stem cell (ADASC) implantation within the corneal stroma of patients with advanced keratoconus. Five consecutive patients were selected. Autologous ADASCs were obtained by elective liposuction. ADASCs (3 × 10) contained in 1 mL saline were injected into the corneal stroma through a femtosecond-assisted 9.5-mm diameter lamellar pocket under topical anesthesia. Patients were reviewed at 1 day, 1 week, 1, 3, and 6 months postoperatively. Visual function, manifest refraction, slit-lamp biomicroscopy, intraocular pressure, endothelial cell density, corneal topography, corneal optical coherence tomography, and corneal confocal biomicroscopy were recorded. No intraoperative or postoperative complications were recorded, with full corneal transparency recovery within 24 hours. Four patients completed the full follow-up. All patients improved their visual function (mean: 1 line of unaided and spectacle-corrected distance vision and 2 lines of rigid contact lens distance vision). Manifest refraction and topographic keratometry remained stable. Corneal optical coherence tomography showed a mean improvement of 16.5 μm in the central corneal thickness, and new collagen production was observed as patchy hyperreflective areas at the level of the stromal pocket. Confocal biomicroscopy confirmed the survival of the implanted stem cells at the surgical plane. Intraocular pressure and endothelial cell density remained stable. Cellular therapy of the human corneal stroma in vivo with autologous ADASCs appears to be safe. Stem cells survive in vivo with intrastromal new collagen production. Future studies with larger samples are required to confirm these preliminary results.

A Systematic Review of Autologous Platelet-Rich Plasma and Fat Graft Preparation Methods

PubMed Central

Smith, Oliver J.; Mosahebi, Afshin

2017-01-01

Background: The addition of platelet-rich plasma (PRP) to adipose tissue may improve fat graft survival, although graft retention rates vary markedly between studies. To what extent this outcome heterogeneity reflects differing methodological factors remains unknown. This systematic review aims to synthesize and critically review methodological approaches to autologous PRP and fat cotransplantation in both human and animal studies. Methods: In accordance with PRISMA guidelines, Ovid MEDLINE, Scopus, and Cochrane Library databases were searched from inception to April 2017. Data were extracted from all in vivo studies involving autologous PRP and fat cotransplantation. A secondary aim was to assess reporting of technical detail; authors were not contacted to provide missing data. Results: From 335 articles, 23 studies were included in the qualitative synthesis. Some 21 were performed in humans and 2 in rabbits. Six studies were randomized control trials; the remainder reported on observational data. Methods of PRP extraction and activation varied markedly between studies. Fat graft preparation was comparatively more consistent. Methods of PRP and fat mixing differed significantly, especially with regards to relative volume/volume ratios. Conclusions: Our study represents the first systematic review of methodological factors in autologous PRP and fat cotransplantation. It demonstrates that technical factors in graft preparation and administration vary significantly between in vivo studies. Such methodological heterogeneity may explain observed differences in experimental and clinical outcomes. Reporting of key procedural information is inconsistent and often inadequate. These issues make meaningful evaluation of the PRP-enhanced fat grafting literature difficult and may limit its translation into clinical practice. PMID:29632775

A Systematic Review of Autologous Platelet-Rich Plasma and Fat Graft Preparation Methods.

PubMed

Luck, Joshua; Smith, Oliver J; Mosahebi, Afshin

2017-12-01

The addition of platelet-rich plasma (PRP) to adipose tissue may improve fat graft survival, although graft retention rates vary markedly between studies. To what extent this outcome heterogeneity reflects differing methodological factors remains unknown. This systematic review aims to synthesize and critically review methodological approaches to autologous PRP and fat cotransplantation in both human and animal studies. In accordance with PRISMA guidelines, Ovid MEDLINE, Scopus, and Cochrane Library databases were searched from inception to April 2017. Data were extracted from all in vivo studies involving autologous PRP and fat cotransplantation. A secondary aim was to assess reporting of technical detail; authors were not contacted to provide missing data. From 335 articles, 23 studies were included in the qualitative synthesis. Some 21 were performed in humans and 2 in rabbits. Six studies were randomized control trials; the remainder reported on observational data. Methods of PRP extraction and activation varied markedly between studies. Fat graft preparation was comparatively more consistent. Methods of PRP and fat mixing differed significantly, especially with regards to relative volume/volume ratios. Our study represents the first systematic review of methodological factors in autologous PRP and fat cotransplantation. It demonstrates that technical factors in graft preparation and administration vary significantly between in vivo studies. Such methodological heterogeneity may explain observed differences in experimental and clinical outcomes. Reporting of key procedural information is inconsistent and often inadequate. These issues make meaningful evaluation of the PRP-enhanced fat grafting literature difficult and may limit its translation into clinical practice.

Functional characterization of a regulatory human T-cell subpopulation increasing during autologous MLR.

PubMed Central

Cosulich, M E; Risso, A; Canonica, G W; Bargellesi, A

1986-01-01

The present study was undertaken to investigate the heterogeneity of helper T cells in humans using two different monoclonal antibodies: 5/9 and MLR4. The former identifies 15-20% of resting T lymphocytes from peripheral blood and corresponds to an anti-helper/inducer T cell. The second antibody, MLR4, recognizes 5% of total T lymphocytes and partially overlaps with the 5/9+ T cells. In order to investigate functional differences within the 5/9+ cells, we separated two different subsets (5/9+ MLR+ and 5/9+ MLR4-) by a rosetting technique. Although both subsets provide help for Ig synthesis in a PWM-stimulated culture, only the 5/9+ MLR4- fraction gave a proliferative response in both autologous and allogeneic MLR and to soluble protein antigens. The effect of radiation on the ability of the two subsets to provide help for Ig synthesis showed that the 5/9+ MLR4+ subset is highly radiation-sensitive, while 5/9+ MLR- is relatively radiation-resistant. In a further series of experiments, 5/9+ MLR4+ cells isolated after activation in an autologous MLR but not by Con A, were no longer able to induce T-cell differentiation but now showed a strong suppressor effect. The 5/9+ MLR4- subset separated from the same cultures did not display any suppressor function. These data demonstrate in fresh PBL the existence of a radiation-sensitive regulatory subset exerting a helper activity, and which acquires suppressor activity after activation in autologous MLR. PMID:2936679

Clinical analysis of thoracoscopic surgery combined with intraoperative autologous blood transfusion in the treatment of traumatic hemothorax.

PubMed

Ma, Hu-Sai; Ma, Ju-Hua; Xue, Feng-Lai; Fu, Xiang-Ning; Zhang, Ni

2016-12-01

From January 2013 to January 2015, 19 patients of traumatic hemothorax with hemorrhagic shock were treated in our department by thoracoscopic surgery combined with autologous blood transfusion. This study retrospectively analyzed the therapeutic effect and shared our experience. The average amount of blood transfused back was 662.41 ml ± 269.15 ml. None of the patients developed transfusion reaction and were all discharged uneventfully. Thoracoscopic surgery combined with autologous blood trans- fusion is effective in the rescue of patients with progressive hemothorax and hemorrhagic shock. When corresponding indications are well managed, treatment for these patients is quicker, safer, and more effective.

A Phase III Clinical Trial Showing Limited Efficacy of Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury.

PubMed

Oh, Sun Kyu; Choi, Kyoung Hyo; Yoo, Jong Yoon; Kim, Dae Yul; Kim, Sang Joon; Jeon, Sang Ryong

2016-03-01

In our previous report, 3 of 10 patients with spinal cord injury who were injected with autologous mesenchymal stem cells (MSCs) showed motor improvement in the upper extremities and in activities of daily living. To report on the results of a phase III clinical trial of autologous MSCs therapy. Patients were selected based on the following criteria: chronic American Spinal Injury Association B status patients who had more than 12 months of cervical injury, and no neurological changes during the recent 3 months of vigorous rehabilitation. We injected 1.6 × 10 autologous MSCs into the intramedullary area at the injured level and 3.2 × 10 autologous MSCs into the subdural space. Outcome data were collected over 6 months regarding neurological examination, magnetic resonance imaging with diffusion tensor imaging, and electrophysiological analyses. Among the 16 patients, only 2 showed improvement in neurological status (unilateral right C8 segment from grade 1 to grade 3 in 1 patient and bilateral C6 from grade 3 to grade 4 and unilateral right C8 from grade 0 to grade 1 in 1 patient). Both patients with neurological improvement showed the appearance of continuity in the spinal cord tract by diffusion tensor imaging. There were no adverse effects associated with MSCs injection. Single MSCs application to intramedullary and intradural space is safe, but has a very weak therapeutic effect compared with multiple MSCs injection. Further clinical trials to enhance the effect of MSCs injection are necessary.

A phase I trial of NK-92 cells for refractory hematological malignancies relapsing after autologous hematopoietic cell transplantation shows safety and evidence of efficacy

PubMed Central

Williams, Brent A.; Law, Arjun Datt; Routy, Bertrand; denHollander, Neal; Gupta, Vikas; Wang, Xing-Hua; Chaboureau, Amélie; Viswanathan, Sowmya; Keating, Armand

2017-01-01

Background Autologous NK cell therapy can treat a variety of malignancies, but is limited by patient-specific variations in potency and cell number expansion. In contrast, allogeneic NK cell lines can overcome many of these limitations. Cells from the permanent NK-92 line are constitutively activated, lack inhibitory receptors and appear to be safe based on two prior phase I trials. Materials and Methods We conducted a single-center, non-randomized, non-blinded, open-label, Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory hematological malignancies who relapsed after autologous hematopoietic cell transplantation (AHCT). The objectives were to determine safety, feasibility and evidence of activity. Patients were treated at one of three dose levels (1 × 109 cells/m2, 3 × 109 cells/m2 and 5 × 109 cells/m2), given on day 1, 3 and 5 for a planned total of six monthly cycles. Results Twelve patients with lymphoma or multiple myeloma who relapsed after AHCT for relapsed/refractory disease were enrolled in this trial. The treatment was well tolerated, with minor toxicities restricted to acute infusional events, including fever, chills, nausea and fatigue. Two patients achieved a complete response (Hodgkin lymphoma and multiple myeloma), two patients had minor responses and one had clinical improvement on the trial. Conclusions Irradiated NK-92 cells can be administered at very high doses with minimal toxicity in patients with refractory blood cancers, who had relapsed after AHCT. We conclude that high dose NK-92 therapy is safe, shows some evidence of efficacy in patients with refractory blood cancers and warrants further clinical investigation. PMID:29179517

Kinetics of prostaglandin E2 and thromboxane A2 synthesis and suppression of PHA-stimulated peripheral blood mononuclear leucocytes.

PubMed Central

Awara, W; Hillier, K; Jones, D

1986-01-01

The immunomodulatory effects of thromboxane A2 and prostaglandin E2 on peripheral blood mononuclear leucocytes stimulated with PHA in vitro, and the relationship of this to the time-course of their synthesis in culture, were investigated using prostaglandin E2, a thromboxane A2 synthesis inhibitor (UK37248), a thromboxane A2 mimic (U46619) and a thromboxane A2 receptor blocker (EP045). The inhibitory effect of prostaglandin E2 on PHA-induced human peripheral blood mononuclear leucocyte proliferation diminishes if the addition of PGE2 is delayed. If added 4 hr after a maximum concentration of PHA (5 micrograms/ml), the effect of PGE2 was reduced by 60%. If a submaximal concentration of PHA (1 microgram/ml) was used, the effect of PGE2 was not reduced if added 4 hr later but fell by about 60% after 16 hr. UK37248 moderately inhibited PHA-induced activation while substantially inhibiting thromboxane A2 synthesis and simultaneously enhancing PGE2 synthesis. The enhanced accumulation of PGE2 occurs while sensitivity to PGE2 is dropping. U46619, exogenously applied as a thromboxane A2 mimic, inhibited PHA-induced activation at concentrations that did not significantly alter PGE2 synthesis. EP045, which may modulate the effects of endogenous thromboxane A2 by blocking receptors, did not alter PHA-induced activation. We conclude that thromboxane A2 may have a role in inhibiting PHA-induced activation on the basis of the effect of U46619. However, this study highlights difficulties in utilizing prostaglandin and thromboxane receptor and synthesis inhibitors to examine their endogenous role in the modulation of mitogen-induced activation in vitro. If sensitivity to the purported endogenous substance is limited to the early stages of culture and if only low levels are synthesized at this early stage, then blocking drugs would have little effect. PMID:3468061

Paroxysmal nocturnal haemoglobinuria phenotype cells and leucocyte subset telomere length in childhood acquired aplastic anaemia.

PubMed

Tutelman, Perri R; Aubert, Geraldine; Milner, Ruth A; Dalal, Bakul I; Schultz, Kirk R; Deyell, Rebecca J

2014-03-01

The significance of paroxysmal nocturnal haemoglobinuria (PNH(pos) ) cells and leucocyte subset telomere lengths in paediatric aplastic anaemia (AA) is unknown. Among 22 children receiving immunosuppressive therapy (IST) for AA, 73% (16/22) were PNH(pos) , of whom 94% achieved at least a partial response (PR) to IST; 11/16 (69%) achieved complete response (CR). Only 2/6 (33%) PNH(neg) patients achieved PR. PNH(pos) patients were less likely to fail IST compared to PNH(neg) patients (odds ratio 0·033; 95% confidence interval 0·002-0·468; P = 0·012). Children with AA had short granulocyte (P = 7·8 × 10(-9) ), natural killer cell (P = 6·0 × 10(-4) ), naïve T lymphocyte (P = 0·002) and B lymphocyte (P = 0·005) telomeres compared to age-matched normative data. © 2013 John Wiley & Sons Ltd.

[Autologous bone marrow transplantation in intestinal carcinoma].

PubMed

Sebesta, C; Tiefengraber, E; Kier, P; Ruckser, R; Habertheuer, K H; Schmid, A; Hinterberger, W

1995-01-01

Although adjuvant chemotherapy has made some progress in the treatment of colorectal cancer, chemotherapy of metastatic disease remains disappointing. Autologous bone marrow or stem cell transplantation following supralethal chemotherapy is presently not of major significance in tumors of the intestine. The registry of the EBMT (European Cooperative Group for Blood and Marrow Transplantation) contains at March 1993 a total of 2085 cases of autotransplants for solid tumors, of which only 19 were performed for disseminated gastrointestinal cancer (15 gastric, 4 colon). It remains to be shown, whether the presently poor results can be improved upon inclusion of lymphokine-activated killer cells (LAK-cells) by use of cytokine combinations or by the use of tumor infiltrating lymphocytes (TIL) post transplantation.

Autologous implantation of BMP2-expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones.

PubMed

Ishihara, Akikazu; Weisbrode, Steve E; Bertone, Alicia L

2015-10-01

Cell-mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein-2 (BMP2) gene transduction. Autologous DFb or BMP2-expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra-medullar infusion into tibiae and delayed intra-osseous injection into femoral drill defects. Both delivery methods of DFb-BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non-transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra-osseous injection of DFb-BMP2. Our results suggested that BMP2-expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb-BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Distinct evolutionary strategies of human leucocyte antigen loci in pathogen-rich environments

PubMed Central

Sanchez-Mazas, Alicia; Lemaître, Jean-François; Currat, Mathias

2012-01-01

Human leucocyte antigen (HLA) loci have a complex evolution where both stochastic (e.g. genetic drift) and deterministic (natural selection) forces are involved. Owing to their extraordinary level of polymorphism, HLA genes are useful markers for reconstructing human settlement history. However, HLA variation often deviates significantly from neutral expectations towards an excess of genetic diversity. Because HLA molecules play a crucial role in immunity, this observation is generally explained by pathogen-driven-balancing selection (PDBS). In this study, we investigate the PDBS model by analysing HLA allelic diversity on a large database of 535 populations in relation to pathogen richness. Our results confirm that geographical distances are excellent predictors of HLA genetic differentiation worldwide. We also find a significant positive correlation between genetic diversity and pathogen richness at two HLA class I loci (HLA-A and -B), as predicted by PDBS, and a significant negative correlation at one HLA class II locus (HLA-DQB1). Although these effects are weak, as shown by a loss of significance when populations submitted to rapid genetic drift are removed from the analysis, the inverse relationship between genetic diversity and pathogen richness at different loci indicates that HLA genes have adopted distinct evolutionary strategies to provide immune protection in pathogen-rich environments. PMID:22312050

Ex-vivo expansion of CFU-GM and BFU-E in unselected PBMC cultures with Flt3L is enhanced by autologous plasma.

PubMed

Guo, M; Miller, W M; Papoutsakis, E T; Patel, S; James, C; Goolsby, C; Winter, J N

1999-01-01

Previous ex-vivo expansion studies in our laboratory, comparing unselected and CD34(+)-selected PBMC, have shown no advantage for CD34(+) cell selection, in terms of the expansion achieved. Our goal was to develop procedures for consistent generation of large numbers of hematopoietic progenitor and post-progenitor cells from unselected PBMC. Unselected PBMC, collected from cancer patients undergoing apheresis prior to high-dose chemotherapy and autologous stem cell rescue, were expanded ex vivo in static cultures, without a stromal layer, in the presence of Flt3 ligand (Flt3L), a recombinant GM-CSF/IL-3 fusion protein (PIXY321), G-CSF and GM-CSF for 10 days. The addition of 2% autologous plasma to this cytokine combination enhanced expansion of total cell numbers (3.2 fold versus 1.9 fold; p < 0.01), colony-forming units granulocyte-macrophage (CFU-GM) (22.0 fold versus 8.1 fold, p < 0.01) and burst-forming units erythroid (BFU-E) (17.6 fold versus 7.0 fold, 0.01 < p < 0.02). The optimal seeding density for a given specimen was inversely related to the frequency of CD34(+) cells in the sample. CFU-GM expansion with the Flt3L-containing cytokine cocktail was equivalent to that obtained with IL-3, IL-6, G-CSF and SCF, whether or not the cultures were supplemented with autologous plasma. In plasma-free cultures, BFU-E expansion was significantly higher with IL-3, IL-6, G-CSF and SCF than with Flt3L, PIXY321, G-CSF and GM-CSF. In the presence of autologous plasma, however BFU-E expansion was higher in the Flt3L-containing media. In comparison studies, autologous plasma suppressed BFU-E expansion in SCF-containing cultures. Consistent with our colony assay results, dual-parameter flow cytometric analysis of the expanded cell population revealed that supplementation with autologous plasma yielded a significant increase in the numbers of myeloid progenitors in Flt3L-containing cultures. Unselected PBMC from cancer patients can be effectively expanded ex vivo in Flt3L

[Effect of autologous platelet-rich plasma on heart infarction in sheep].

PubMed

Gallo, Ignacio; Sáenz, Alberto; Arévalo, Adolfo; Roussel, Sonia; Pérez-Moreiras, Ignacio; Artiñano, Edurne; Martínez-Peñuela, Ana; Esquide, Javier; Aspiroz, Antonio; Camacho, Ignacio

2013-01-01

Myocardial infarction is the most common cause of congestive heart failure. The objective of this work is to evaluate, in experimental animals, morphological and histological effects of the implantation of autologous platelet-rich plasma in infarcted heart sheep. Twenty-four ewes were used, they were surgically infarcted through left thoracotomy and two coronary arteries were ligated (first and second diagonal). After coronary artery ligation three sheep died of ventricular fibrillation. Three weeks after coronary ligation, sheep were reoperated through median sternotomy. Normal saline solution was injected in the infarcted zone in 6 of them (control group) whereas platelet gel was injected in 15 of them. All sheep were euthanized at 9 weeks of evolution of the second surgery. Noteworthy is the formation of new vessels in hematoxylin-eosin-stained sections and factor viii in plasma rich in growth-factors (PRGF)-treated hearts. Injection of platelet growth factors, PRGF, in previously infarcted sheep hearts promotes mitogenesis and angiogenesis. The use of autologous PRGF is simple and safe, causing no toxicity or immune-inflammatory reactions. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells.

PubMed

Burkhardt, Ute E; Hainz, Ursula; Stevenson, Kristen; Goldstein, Natalie R; Pasek, Mildred; Naito, Masayasu; Wu, Di; Ho, Vincent T; Alonso, Anselmo; Hammond, Naa Norkor; Wong, Jessica; Sievers, Quinlan L; Brusic, Ana; McDonough, Sean M; Zeng, Wanyong; Perrin, Ann; Brown, Jennifer R; Canning, Christine M; Koreth, John; Cutler, Corey; Armand, Philippe; Neuberg, Donna; Lee, Jeng-Shin; Antin, Joseph H; Mulligan, Richard C; Sasada, Tetsuro; Ritz, Jerome; Soiffer, Robert J; Dranoff, Glenn; Alyea, Edwin P; Wu, Catherine J

2013-09-01

Patients with advanced hematologic malignancies remain at risk for relapse following reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a prospective clinical trial to test whether vaccination with whole leukemia cells early after transplantation facilitates the expansion of leukemia-reactive T cells and thereby enhances antitumor immunity. We enrolled 22 patients with advanced chronic lymphocytic leukemia (CLL), 18 of whom received up to 6 vaccines initiated between days 30 and 45 after transplantation. Each vaccine consisted of irradiated autologous tumor cells admixed with GM-CSF-secreting bystander cells. Serial patient PBMC samples following transplantation were collected, and the impact of vaccination on T cell activity was evaluated. At a median follow-up of 2.9 (range, 1-4) years, the estimated 2-year progression-free and overall survival rates of vaccinated subjects were 82% (95% CI, 54%-94%) and 88% (95% CI, 59%-97%), respectively. Although vaccination only had a modest impact on recovering T cell numbers, CD8+ T cells from vaccinated patients consistently reacted against autologous tumor, but not alloantigen-bearing recipient cells with increased secretion of the effector cytokine IFN-γ, unlike T cells from nonvaccinated CLL patients undergoing allo-HSCT. Further analysis confirmed that 17% (range, 13%-33%) of CD8+ T cell clones isolated from 4 vaccinated patients by limiting dilution of bulk tumor-reactive T cells solely reacted against CLL-associated antigens. Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control following allo-HSCT. Clinicaltrials.gov NCT00442130. NCI (5R21CA115043-2), NHLBI (5R01HL103532-03), and Leukemia and Lymphoma Society Translational Research Program.

Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells.

PubMed Central

Gillies, S D; Reilly, E B; Lo, K M; Reisfeld, R A

1992-01-01

A genetically engineered fusion protein consisting of a chimeric anti-ganglioside GD2 antibody (ch14.18) and interleukin 2 (IL2) was tested for its ability to enhance the killing of autologous GD2-expressing melanoma target cells by a tumor-infiltrating lymphocyte line (660 TIL). The fusion of IL2 to the carboxyl terminus of the immunoglobulin heavy chain did not reduce IL2 activity as measured in a standard proliferation assay using either mouse or human T-cell lines. Antigen-binding activity was greater than that of the native chimeric antibody. The ability of resting 660 TIL cells to kill their autologous GD2-positive target cells was enhanced if the target cells were first coated with the fusion protein. This stimulation of killing was greater than that of uncoated cells in the presence of equivalent or higher concentrations of free IL2. Such antibody-cytokine fusion proteins may prove useful in targeting the biological effect of IL2 and other cytokines to tumor cells and in this way stimulate their immune destruction. Images PMID:1741398

Outcomes of autologous or allogeneic stem cell transplantation for non-Hodgkin lymphoma.

PubMed

Reddy, Nishitha M; Oluwole, Olalekan; Greer, John P; Engelhardt, Brian G; Jagasia, Madan H; Savani, Bipin N

2014-01-01

Transplant outcomes of autologous or allogeneic stem cell transplantation (SCT) have not been elucidated as a single cohort in non-Hodgkin lymphoma (NHL). We analyzed the outcomes of 270 adult recipients receiving autologous (auto) SCT (n = 198) or allogeneic (allo) SCT (n = 72) for NHL between the years 2000 and 2010. Five-year overall survival rates for B and T cell NHL were 58% and 50%, respectively (allo-SCT 51% vs. 54% for B and T-cell NHL, and auto-SCT 60% vs. 47% for B and T cell lymphoma, respectively). In multivariate analysis, the number of chemotherapy regimens and disease status pre-SCT were independently associated with long-term outcome after SCT (for both auto- and allo-SCT). We conclude that the type of transplantation offered to patients, based on patient selection and disease-related factors, can achieve long-term survival, highlighting the importance of further improvement in disease control and reducing procedure-related mortality. The role of transplantation needs to be reevaluated in the era of targeted therapy. Copyright © 2014 ISEH - Society for Hematology and Stem Cells. All rights reserved.

Autologous platelet-rich plasma as an adipocyte in vivo delivery system: case report.

PubMed

Azzena, Bruno; Mazzoleni, Francesco; Abatangelo, Giovanni; Zavan, Barbara; Vindigni, Vincenzo

2008-01-01

Tissue engineering has emerged as a promising alternative to current clinical treatments for restoration of soft tissue defects. A key element in the process of tissue engineering is an ideal implant that provides structural support and a favorable environment for growing cells. The authors hypothesized that autologous platelet-rich plasma (APRP) could be used as an in vivo adipocyte delivery system to favor cell survival and to stimulate early recruitment of microcapillaries to the site of implantation. Autologous fat was included in APRP and injected as a gel into a subcutaneous pocket created to correct a painful, adherent scar at the shoulder level in a 75-year-old woman. The surgical outcome was evaluated by histologic and immunohistochemical analysis as well as by ecography before and after surgery. The results were satisfactory, showing fat survival 1 year after surgery. The characteristics of this new material should stimulate research into future clinical applications for such cell constructs in plastic and reconstructive surgery.

Clinical outcomes after the use of complete autologous oral mucosa equivalents: preliminary cases.

PubMed

Peña, Ignacio; Junquera, Luis Manuel; Llorente, Santiago; de Villalaín, Lucas; de Vicente, Juan Carlos; Llames, Sara

2012-05-01

Previously, we reported how to obtain complete autologous oral mucosa equivalents (CAOMEs) composed of an autologous plasma scaffold and fibroblasts together with immature keratinocytes able to build an oral epithelium with a structure similar to that of the oral mucosa. In this study, we present the clinical outcomes after applying our CAOMEs as grafts. Four patients who needed a CAOME to restore a defect of oral mucosa were selected. Two of the patients suffered from ankyloglossia, and the other 2 required a restoration of the keratinized gum of the alveolar rim. To assess the outcomes, the scale designed by Ewers et al. was used. Clinical and functional improvements were achieved in the patients with ankyloglossia. In cases of gum restoration, the mucosa was regenerated and a prosthetic restoration with implants was achieved. The results obtained points to the potential use of CAOME in intraoral lining. Copyright © 2012 Elsevier Inc. All rights reserved.

Renal Allograft Survival in Nonhuman Primates Infused with Donor Antigen-Pulsed Autologous Regulatory Dendritic Cells

PubMed Central

Ezzelarab, M.B.; Raich-Regue, D.; Lu, L.; Zahorchak, A.F.; Perez-Gutierrez, A.; Humar, A.; Wijkstrom, M.; Minervini, M.; Wiseman, R.W.; Cooper, D.K.C.; Morelli, A.E.; Thomson, A.W.

2017-01-01

Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg pre-loaded with cell membrane vesicles from allogeneic PBMC, induce T cell hyporesponsiveness to donor alloAg in vitro. These donor alloAg-pulsed autologous DCreg (1.4–3.6 x 106/kg) were administered intravenously, one day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 [CTLA4] Ig) and tapered rapamycin. Prolongation of graft median survival time from 39.5 days (no DCreg infusion; n=6 historical controls) and 29 days with control unpulsed DCreg (n=2), to 56 days with donor Ag-pulsed DCreg (n=5), was associated with evidence of modulated host CD4+ and CD8+ T cell responses to donor Ag and attenuation of systemic IL-17 production. Circulating anti-donor antibody (Ab) was not detected until CTLA4Ig withdrawal. One monkey treated with donor Ag-pulsed DCreg rejected its graft in association with progressively elevated anti-donor Ab, 525 days post-transplant (160 days after withdrawal of immunosuppression). These findings indicate a modest but not statistically significant beneficial effect of donor Ag-pulsed autologous DCreg infusion on NHP graft survival when administered with a minimal immunosuppressive drug regimen. PMID:28009481

From fresh heterologous oocyte donation to autologous oocyte banking

PubMed Central

Stoop, D.

2012-01-01

Introduction: Today, oocyte donation has become well established, giving rise to thousands of children born worldwide annually. The introduction of oocyte cryopreservation through vitrification allows the introduction of egg banking, improving the efficiency and comfort of oocyte donation. Moreover, the vitrification technique can now enable autologous donation of oocytes to prevent future infertility. Methods: We evaluated fresh heterologous oocyte donation in terms of obstetrical and perinatal outcome as well as of the reproductive outcome of past donors. We then evaluated the efficiency of a closed vitrification device and its clinical applications within ART. Thirdly, we evaluated the opinion of women with regard to preventive egg freezing and the efficiency of a human oocyte in relation to age. Results: Oocyte donation is associated with an increased risk of first trimester bleeding and pregnancy induced hypertension. Donating oocytes does not seem to increase the likelihood for a later need of fertility treatment. The chance of an oocyte to result in live birth (utilization rate) in women <37 years old remains constant with a mean of 4.47%. A significant proportion of young women would consider safeguarding their reproductive potential through egg freezing or are at least open to the idea. Discussion and Conclusion: The introduction of efficient oocyte cryopreservation has revolutionized oocyte donation through the establishment of eggbank donation. The technique also enables women to perform autologous donation after preventive oocyte storage in order to circumvent their biological clock. PMID:24753920

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

DOE PAGES

Moody, M.  Anthony; Gao, Feng; Gurley, Thaddeus  C.; ...

2015-09-09

The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tiermore » 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.« less

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses.

PubMed

Moody, M Anthony; Gao, Feng; Gurley, Thaddeus C; Amos, Joshua D; Kumar, Amit; Hora, Bhavna; Marshall, Dawn J; Whitesides, John F; Xia, Shi-Mao; Parks, Robert; Lloyd, Krissey E; Hwang, Kwan-Ki; Lu, Xiaozhi; Bonsignori, Mattia; Finzi, Andrés; Vandergrift, Nathan A; Alam, S Munir; Ferrari, Guido; Shen, Xiaoying; Tomaras, Georgia D; Kamanga, Gift; Cohen, Myron S; Sam, Noel E; Kapiga, Saidi; Gray, Elin S; Tumba, Nancy L; Morris, Lynn; Zolla-Pazner, Susan; Gorny, Miroslaw K; Mascola, John R; Hahn, Beatrice H; Shaw, George M; Sodroski, Joseph G; Liao, Hua-Xin; Montefiori, David C; Hraber, Peter T; Korber, Bette T; Haynes, Barton F

2015-09-09

The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses. Copyright © 2015 Elsevier Inc. All rights reserved.

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moody, M.  Anthony; Gao, Feng; Gurley, Thaddeus  C.

The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tiermore » 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.« less

HIV-1 Autologous Antibody Neutralization Associates with Mother to Child Transmission

PubMed Central

Baan, Elly; de Ronde, Anthony; Stax, Martijn; Sanders, Rogier W.; Luchters, Stanley; Vyankandondera, Joseph; Lange, Joep M.; Pollakis, Georgios; Paxton, William A

2013-01-01

The HIV-1 characteristics associated with mother to child transmission (MTCT) are still poorly understood and if known would indicate where intervention strategies should be targeted. In contrast to horizontally infected individuals, exposed infants possess inherited antibodies (Abs) from their mother with the potential to protect against infection. We investigated the HIV-1 gp160 envelope proteins from seven transmitting mothers (TM) whose children were infected either during gestation or soon after delivery and from four non-transmitting mothers (NTM) with similar viral loads and CD4 counts. Using pseudo-typed viruses we tested gp160 envelope glycoproteins for TZM-bl infectivity, CD4 and CCR5 interactions, DC-SIGN capture and transfer and neutralization with an array of common neutralizing Abs (NAbs) (2F5, 2G12, 4E10 and b12) as well as mother and infant plasma. We found no viral correlates associated with HIV-1 MTCT nor did we find differences in neutralization with the panel of NAbs. We did, however, find that TM possessed significantly higher plasma neutralization capacities than NTM (P  = 0.002). Furthermore, we found that in utero (IU) TM had a higher neutralization capacity than mothers transmitting either peri - partum (PP) or via breastfeeding (BF) (P  = 0.002). Plasma from children infected IU neutralized viruses carrying autologous gp160 viral envelopes as well as those from their corresponding mothers whilst plasma from children infected PP and/or BF demonstrated poor neutralizing capacity. Our results demonstrate heightened autologous NAb responses against gp120/gp41 can associate with a greater risk of HIV-1 MTCT and more specifically in those infants infected IU. Although the number of HIV-1 transmitting pairs is low our results indicate that autologous NAb responses in mothers and infants do not protect against MTCT and may in fact be detrimental when considering IU HIV-1 transmissions. PMID:23874931

Effects of Autologous Fat and ASCs on Swine Hypertrophic Burn Scars: A Multimodal Quantitative Analysis

PubMed Central

Pan, Brian S.; Schwentker, Ann R.; Van Aalst, John

2017-01-01

Background: Hypertrophic scar formation is unpredictable and poorly understood, afflicting both the pediatric and adult populations. Treatment methods with conservative and invasive approaches have low rates of compliance and high rates of morbidity. The purpose of this study was to test a reproducible scar model and investigate a new technique of scar modification through the use of adipose- derived progenitor stromal cells (ASCs). Methods: Twenty thermal deep-partial thickness contact burns were created on the dorsum of three 8-week-old domestic swine and allowed to mature for 10 weeks. Scars were then injected with 2 cc saline, expanded autologous ASCs, or 2 cc fresh lipoaspirate and sampled at 2 week intervals up to 10 weeks postinjection. Volumetric analysis with a 3-D scanner, mechanical elasticity testing through negative pressure transduction, and standardized photography evaluation with Image J was performed. RNA sequencing was performed on scar tissue samples, cultured cells, and fresh lipoaspirate to determine relevant gene transcription regulation. Immunohistochemistry was used to verify expression level changes within the scars. Results: Volumetric analysis demonstrates a reduction in average scar thickness at 6 weeks when injected with ASCs (−1.6 cc3) and autologous fat (−1.95 cc3) relative to controls (−0.121 cc3; P < 0.05). A decrease in overall tissue compliance is observed with fat or ASC injection when compared with unburned skin at 8 weeks (35.99/37.94 versus 49.36 mm Hg × mm; P < 0.01). RNA sequencing demonstrates altered regulation of fibroblast gene expression and a decreased inflammatory profile when scars are injected with autologous fat/ASCs over controls. Conclusion: Early results suggest that autologous fat and/or ASCs may improve healing of hypertrophic scarring by altering the cellular and structural components during wound remodeling up to 20 weeks after injury. This may have beneficial applications in early treatment of

Flow-aggregated traffic-driven label mapping in label-switching networks

NASA Astrophysics Data System (ADS)

Nagami, Kenichi; Katsube, Yasuhiro; Esaki, Hiroshi; Nakamura, Osamu

1998-12-01

Label switching technology enables high performance, flexible, layer-3 packet forwarding based on the fixed length label information mapped to the layer-3 packet stream. A Label Switching Router (LSR) forwards layer-3 packets based on their label information mapped to the layer-3 address information as well as their layer-3 address information. This paper evaluates the required number of labels under traffic-driven label mapping policy using the real backbone traffic traces. The evaluation shows that the label mapping policy requires a large number of labels. In order to reduce the required number of labels, we propose a label mapping policy which is a traffic-driven label mapping for the traffic toward the same destination network. The evaluation shows that the proposed label mapping policy requires only about one tenth as many labels compared with the traffic-driven label mapping for the host-pair packet stream,and the topology-driven label mapping for the destination network packet stream.

Nutrition Label Viewing during a Food-Selection Task: Front-of-Package Labels vs Nutrition Facts Labels.

PubMed

Graham, Dan J; Heidrick, Charles; Hodgin, Katie

2015-10-01

Earlier research has identified consumer characteristics associated with viewing Nutrition Facts labels; however, little is known about those who view front-of-package nutrition labels. Front-of-package nutrition labels might appeal to more consumers than do Nutrition Facts labels, but it might be necessary to provide consumers with information about how to locate and use these labels. This study quantifies Nutrition Facts and front-of-package nutrition label viewing among American adult consumers. Attention to nutrition information was measured during a food-selection task. One hundred and twenty-three parents (mean age=38 years, mean body mass index [calculated as kg/m(2)]=28) and one of their children (aged 6 to 9 years) selected six foods from a university laboratory-turned-grocery aisle. Participants were randomized to conditions in which front-of-package nutrition labels were present or absent, and signage explaining front-of-package nutrition labels was present or absent. Adults' visual attention to Nutrition Facts labels and front-of-package nutrition labels was objectively measured via eye-tracking glasses. To examine whether there were significant differences in the percentages of participants who viewed Nutrition Facts labels vs front-of-package nutrition labels, McNemar's tests were conducted across all participants, as well as within various sociodemographic categories. To determine whether hypothesized factors, such as health literacy and education, had stronger relationships with front-of-package nutrition label vs Nutrition Facts label viewing, linear regression assessed the magnitude of relationships between theoretically and empirically derived factors and each type of label viewing. Overall, front-of-package nutrition labels were more likely to be viewed than Nutrition Facts labels; however, for all subgroups, higher rates of front-of-package nutrition label viewership occurred only when signage was present drawing attention to the presence and

Autologous Fat Transfer in Secondary Carpal Tunnel Release

PubMed Central

Noszczyk, Bartłomiej H.

2015-01-01

Background: Carpal tunnel release is the gold standard for the treatment of median nerve compression disease. Recurrent or persistent symptoms do not occur in most patients, although a small number of them have indicated that such a postoperative condition indeed exists. Some patients undergo repeated treatments. In the majority of the cases, the disease is associated with scarring in the carpal tunnel or even reformation of the carpal ligament. The authors propose the usage of autologous fat grafting during secondary carpal tunnel release to inhibit the scarring process. Methods: Ten patients with recurrent or persistent symptoms underwent autologous fat grafting at the time of their repeated carpal tunnel release. Fat was harvested from the lower abdomen and grafted into the scarred transverse carpal ligament and surrounding tissues. Each patient underwent pre- and postoperative examinations and completed the carpal tunnel questionnaire (Boston) to evaluate their sensory and motor functions. The patients underwent 1 year of follow-up. Results: There were 2 main reasons for continued symptoms: a technical mistake resulting in incomplete release (IR) during the first operation and abundant scarring (ABS) in the operated area. The beneficial effects of the interventions were confirmed by a clinical study and by administering the carpal tunnel questionnaire to all patients (functional severity score decreased from 4.38 to 1.88 in IR and 3.62 to 1.48 in ABS group, sensory severity score from 3.26 to 1.7 in IR and 3.04 to 1.48 in ABS group; P < 0.05) after 12 months of follow-up. Conclusion: Our initial observations suggest the possible efficacy of adipose tissue in secondary carpal tunnel release. PMID:26090291

Co-Labeling for Multi-View Weakly Labeled Learning.

PubMed

Xu, Xinxing; Li, Wen; Xu, Dong; Tsang, Ivor W

2016-06-01

It is often expensive and time consuming to collect labeled training samples in many real-world applications. To reduce human effort on annotating training samples, many machine learning techniques (e.g., semi-supervised learning (SSL), multi-instance learning (MIL), etc.) have been studied to exploit weakly labeled training samples. Meanwhile, when the training data is represented with multiple types of features, many multi-view learning methods have shown that classifiers trained on different views can help each other to better utilize the unlabeled training samples for the SSL task. In this paper, we study a new learning problem called multi-view weakly labeled learning, in which we aim to develop a unified approach to learn robust classifiers by effectively utilizing different types of weakly labeled multi-view data from a broad range of tasks including SSL, MIL and relative outlier detection (ROD). We propose an effective approach called co-labeling to solve the multi-view weakly labeled learning problem. Specifically, we model the learning problem on each view as a weakly labeled learning problem, which aims to learn an optimal classifier from a set of pseudo-label vectors generated by using the classifiers trained from other views. Unlike traditional co-training approaches using a single pseudo-label vector for training each classifier, our co-labeling approach explores different strategies to utilize the predictions from different views, biases and iterations for generating the pseudo-label vectors, making our approach more robust for real-world applications. Moreover, to further improve the weakly labeled learning on each view, we also exploit the inherent group structure in the pseudo-label vectors generated from different strategies, which leads to a new multi-layer multiple kernel learning problem. Promising results for text-based image retrieval on the NUS-WIDE dataset as well as news classification and text categorization on several real-world multi

Implantation of Autologous Cartilage Chips Improves Cartilage Repair Tissue Quality in Osteochondral Defects: A Study in Göttingen Minipigs.

PubMed

Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Olesen, Morten Lykke; Hede, Kris Chadwick; Lind, Martin

2016-06-01

Osteochondral injuries have poor endogenous healing potential, and no standard treatment has been established. The use of combined layered autologous bone and cartilage chips for treatment of osteochondral defects has shown promising short-term clinical results. This study aimed to investigate the role of cartilage chips by comparing combined layered autologous bone and cartilage chips with autologous bone implantation alone in a Göttingen minipig model. The hypothesis was that the presence of cartilage chips would improve the quality of the repair tissue. Controlled laboratory study. Twelve Göttingen minipigs received 2 osteochondral defects in each knee. The defects were randomized to autologous bone graft (ABG) combined with autologous cartilage chips (autologous dual-tissue transplantation [ADTT]) or ABG alone. Six animals were euthanized at 6 months and 6 animals were euthanized at 12 months. Follow-up evaluation consisted of histomorphometry, immunohistochemistry, semiquantitative scoring (International Cartilage Repair Society II), and computed tomography. There was significantly more hyaline cartilage in the ADTT group (25.8%) compared with the ABG group (12.8%) at 6 months after treatment. At 12 months, the fraction of hyaline cartilage in the ABG group had significantly decreased to 4.8%, whereas the fraction of hyaline cartilage in the ADTT group was unchanged (20.1%). At 6 and 12 months, there was significantly more fibrocartilage in the ADTT group (44% and 60.8%) compared with the ABG group (24.5% and 41%). The fraction of fibrous tissue was significantly lower in the ADTT group compared with the ABG group at both 6 and 12 months. The implanted cartilage chips stained >75% positive for collagen type 4 and laminin at both 6 and 12 months. Significant differences were found in a number of International Cartilage Repair Society II subcategories. The volume of the remaining bone defect significantly decreased from 6 to 12 months in both treatment groups

Autologous/Allogeneic Hematopoietic Cell Transplantation versus Tandem Autologous Transplantation for Multiple Myeloma: Comparison of Long-Term Postrelapse Survival.

PubMed

Htut, Myo; D'Souza, Anita; Krishnan, Amrita; Bruno, Benedetto; Zhang, Mei-Jie; Fei, Mingwei; Diaz, Miguel Angel; Copelan, Edward; Ganguly, Siddhartha; Hamadani, Mehdi; Kharfan-Dabaja, Mohamed; Lazarus, Hillard; Lee, Cindy; Meehan, Kenneth; Nishihori, Taiga; Saad, Ayman; Seo, Sachiko; Ramanathan, Muthalagu; Usmani, Saad Z; Gasparetto, Christina; Mark, Tomer M; Nieto, Yago; Hari, Parameswaran

2018-03-01

We compared postrelapse overall survival (OS) after autologous/allogeneic (auto/allo) versus tandem autologous (auto/auto) hematopoietic cell transplantation (HCT) in patients with multiple myeloma (MM). Postrelapse survival of patients receiving an auto/auto or auto/allo HCT for MM and prospectively reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2010 were analyzed. Relapse occurred in 404 patients (72.4%) in the auto/auto group and in 178 patients (67.4%) in the auto/allo group after a median follow-up of 8.5 years. Relapse occurred before 6 months after a second HCT in 46% of the auto/allo patients, compared with 26% of the auto/auto patients. The 6-year postrelapse survival was better in the auto/allo group compared with the auto/auto group (44% versus 35%; P = .05). Mortality due to MM was 69% (n = 101) in the auto/allo group and 83% (n = 229) deaths in auto/auto group. In multivariate analysis, both cohorts had a similar risk of death in the first year after relapse (hazard ratio [HR], .72; P = .12); however, for time points beyond 12 months after relapse, overall survival was superior in the auto/allo cohort (HR for death in auto/auto =1.55; P = .005). Other factors associated with superior survival were enrollment in a clinical trial for HCT, male sex, and use of novel agents at induction before HCT. Our findings shown superior survival afterrelapse in auto/allo HCT recipients compared with auto/auto HCT recipients. This likely reflects a better response to salvage therapy, such as immunomodulatory drugs, potentiated by a donor-derived immunologic milieu. Further augmentation of the post-allo-HCT immune system with new immunotherapies, such as monoclonal antibodies, checkpoint inhibitors, and others, merit investigation. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A Safety Study on Intrathecal Delivery of Autologous Mesenchymal Stromal Cells in Rabbits Directly Supporting Phase I Human Trials

PubMed Central

Chen, Bingkun K.; Staff, Nathan P.; Knight, Andrew M.; Nesbitt, Jarred J.; Butler, Greg W.; Padley, Douglas J.; Parisi, Joseph E.; Dietz, Allan B.; Windebank, Anthony J.

2014-01-01

Background There are no effective treatments that slow the progression of neurodegenerative diseases. A major challenge of treatment in neurodegenerative diseases is appropriate delivery of pharmaceuticals into the cerebrospinal fluid (CSF) of affected individuals. Mesenchymal stromal cells (MSCs – either naïve or modified) are a promising therapy in neurodegenerative diseases and may be delivered directly into the CSF where they can reside for months. In this preclinical study, we evaluated the safety of intrathecal autologous MSCs in a rabbit model. Methods Autologous adipose-derived MSCs (or a-CSF) were delivered intrathecally, either with single or repeated injections into the foramen magnum of healthy rabbits, and monitored for 4 and 12 weeks, respectively. Results Rabbits tolerated injections well and no definitive MSC-related side effects were observed apart from three rabbits that had delayed death secondary to traumatic foramen magnum puncture. Functional assessments and body weights were equivalent between groups. Gross pathology and histology did not reveal any abnormalities or tumor growth. Complete blood count (CBC) data were normal and there were no differences in CSF IL-6 levels in all groups tested. Discussion Our data suggest that intrathecal delivery of autologous MSCs is safe in a rabbit model. Data from this study has supported two successful Investigational New Drug (IND) applications to the FDA, resulting in the initiation of two clinical trials using autologous MSCs in amyotrophic lateral sclerosis and multiple system atrophy. PMID:25413276

Elevated serum estradiol levels in artificial autologous frozen embryo transfer cycles negatively impact ongoing pregnancy and live birth rates.

PubMed

Fritz, Rani; Jindal, Sangita; Feil, Heather; Buyuk, Erkan

2017-12-01

The aim of this study is to evaluate the correlation between serum estradiol (E 2 ) levels during artificial autologous frozen embryo transfer (FET) cycles and ongoing pregnancy/live birth rates (OP/LB). A historical cohort study was conducted in an academic setting in order to correlate peak and average estradiol levels with ongoing pregnancy/live birth rates for all autologous artificial frozen embryo transfer cycles performed from 1/2011 to 12/2014. Average and peak E 2 levels from 110 autologous artificial FET cycles from 95 patients were analyzed. Average E 2 levels were significantly lower in cycles resulting in OP/LB compared to those that did not (234.1 ± 16.6 pg/ml vs. 315 ± 24.8 pg/ml, respectively, p = 0.04). Although peak E 2 levels were not significantly different between cycles resulting in OP/LB compared with those that did not (366.9 ± 27.7 pg/ml vs. 459.1 ± 32.3 pg/ml, respectively, p = 0.19), correlation analysis revealed a statistically significant (p = 0.02) downward trend in OP/LB rates with increasing peak E 2 levels. This study suggests that elevated E 2 levels in artificial autologous FET cycles are associated with lower OP/LB rates. Estradiol levels should be monitored during artificial FET cycles.

Characterization of a neutral protease from lysosomes of rabbit polymorphonuclear leucocytes

PubMed Central

Davies, Philip; Rita, Giuseppe A.; Krakauer, Kathrin; Weissmann, Gerald

1971-01-01

1. The subcellular distribution has been investigated of a protease from rabbit polymorphonuclear leucocytes, obtained from peritoneal exudates. The enzyme, optimally active between pH7.0 and 7.5, hydrolyses histone but not haemoglobin, sediments almost exclusively with a granule fraction rich in other lysosomal enzymes, and is latent until the granules are disrupted by various means. 2. Enzymic analysis of specific and azurophilic granules separated by zonal centrifugation showed that neutral protease activity was confined to fractions rich in enzymes characteristic of azurophile granules. 3. Recovery of neutral protease activity from subcellular fractions was several times greater than that found in whole cells. This finding was explained by the presence of a potent inhibitor of the enzyme activity in the cytoplasm. 4. The effect of the inhibitor was reversed by increasing ionic strength (up to 2.5m-potassium chloride) and by polyanions such as heparin and dextran sulphate, but not by an uncharged polymer, dextran. 5. The enzyme was also inhibited, to a lesser extent, by 1-chloro-4-phenyl-3-l-toluene-p-sulphonamidobutan-2-one, soya-bean trypsin inhibitor and ∈-aminohexanoate (∈-aminocaproate). 6. The granule fractions failed to hydrolyse artificial substrates for trypsin and chymotrypsin. 7. Partial separation of the enzyme was achieved by Sephadex gel filtration at high ionic strength and by isoelectric focusing. The partially separated, activated enzyme showed an approximately 300-fold increase in specific activity over that in whole cells. PMID:5126908

Apoptosis of conjunctival epithelial cells before and after the application of autologous serum eye drops in severe dry eye disease.

PubMed

Rybickova, Ivana; Vesela, Viera; Fales, Ivan; Skalicka, Pavlina; Jirsova, Katerina

2016-06-01

To assess the impact of autologous serum eye drops on the level of ocular surface apoptosis in patients with bilateral severe dry eye disease. This prospective study was conducted on 10 patients with severe dry eye due to graft versus host disease (group 1) and 6 patients with severe dry eye due to primary Sjögren's syndrome (group 2). Impression cytology specimens from the bulbar conjunctiva were obtained before and after a three-month treatment with 20% autologous serum eye drops applied a maximum of 12 times a day together with regular therapy with artificial tears. The percentage of apoptotic epithelial cells was evaluated immunochemically using anti-active caspase 3 antibody. In group 1, the mean percentage of apoptotic cells was 3.6% before the treatment. The three-month treatment led to a significant decrease to a mean percentage of 1.8% (P = 0.028). The mean percentage of apoptotic conjunctival cells decreased from 5.4% before the treatment to 3.8% in group 2; however, these results did not reach the level of significance. Three-month autologous serum treatment led to the improvement of ocular surface apoptosis, especially in the group of patients with severe dry eye due to graft versus host disease. This result supports the very positive effect of autologous serum on the ocular surface in patients suffering from severe dry eye.

Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial

PubMed Central

Féron, F.; Cochrane, J.; Bassingthwaighte, L.; Bayliss, C.; Davies, W.; Fronek, P.; Gray, C.; Kerr, G.; Licina, P.; Nowitzke, A.; Perry, C.; Silburn, P.A.S.; Urquhart, S.; Geraghty, T.

2008-01-01

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post

Outcomes in relapsed Hodgkin's lymphoma treated with autologous and allogeneic hematopoietic cell transplantation at the Pontificia Universidad Católica de Chile

PubMed Central

Ramirez, Pablo; Ocqueteau, Mauricio; Rodriguez, Alejandra; Garcia, Maria Jose; Sarmiento, Mauricio; Ernst, Daniel; Jara, Veronica; Bertin, Pablo

2015-01-01

Introduction Hodgkin's lymphoma is a highly curable disease. Autologous and reduced intensity allogeneic hematopoietic cell transplantations are alternatives to treat relapsed patients. Here, we report on the results of one service using these procedures. Methods All patients who underwent transplantations in our institution between 1996 and 2014 were retrospectively studied and demographics, toxicities and survival rate were analyzed. Results This study evaluated 24 autologous and five reduced intensity allogeneic transplantations: the median ages of the patients were 29 and 32 years, respectively. At the time of autologous transplantation, ten patients were in complete remission, nine had chemosensitive disease but were not in complete remission, three had refractory disease and the status of two is unknown. In the allogeneic group, two were in complete remission and three had chemosensitive disease. The 5-year overall survival after autologous transplantation was 42% (66% patients were in complete remission, 37% had chemosensitive disease with incomplete remission and 0% had refractory disease) and 1-year overall survival after allogeneic transplantation was 80%. Transplant-related mortality was 0% in patients conditioned with the ifosfamide/carboplatin/etoposide (ICE), carmustine/etoposide/cyclophosphamide (BEC) and carmustine/etoposide/cytarabine/melphalan (BEAM) regimens, 37% in patients conditioned with busulfan-based regimens and 20% in allogeneic transplantations. Conclusions Hematopoietic cell transplantation for relapsed Hodgkin's lymphoma is a potentially curative procedure especially in patients in complete remission at the time of autologous transplantations, and possibly after allogeneic transplantations. Further studies are necessary to clarify the role of allogeneic transplantations in the treatment of relapsed Hodgkin's lymphoma. PMID:26041421

In vitro effects of Italian Lavandula multifida L. leaf extracts on gilthead seabream (Sparus aurata) leucocytes and SAF-1 cells.

PubMed

Fazio, Angela; Cerezuela, Rebeca; Panuccio, Maria Rosaria; Cuesta, Alberto; Esteban, Maria Ángeles

2017-07-01

Lavandula multifida is very appreciated by pharmaceutical and cosmetic industries. In Italy is only found in Calabria and Sicily and, at present, urge its valorization due to its high extinction and genetic erosion risks. Possible applications of L. multifida extracts as immunostimulant in fish aquaculture were assayed by using gilthead seabream (Sparus aurata) as a marine fish model, due to its importance in fish aquaculture. The in vitro effects of both aqueous and ethanolic leaf extracts obtained from two Italian populations of L. multifida on head kidney leucocyte activities (viability, phagocytosis, respiratory burst and peroxidase content) were assessed. Furthermore, the possible cytotoxic effects of the extracts on SAF-1 cells and their bactericidal effects on three fish pathogenic bacteria (Vibrio harveyi, Vibrio anguillarum, Aeromonas salmonicida) were also evaluated. All the assays were performed in comparison with leaf extracts obtained from a widely-distributed species as L. angustifolia. Results showed that water and ethanolic leaf extracts obtained from L. multifida enhanced innate immune activities of S. aurata HK leucocytes. Furthermore, SAF-1 cell viability was not affected significantly after being incubated with the extracts. These extracts did not exert any bactericidal activity on the pathogenic bacterial strains tested in the present study. Results obtained in the present work suggested the possibility of use such extracts in in vivo studies in order to corroborate the possibility of their use in aquaculture. Their use could prevent to improve fish defense against pathogenic infections through enhancement of the fish immune status. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early Prognostic Value of Monitoring Serum Free Light Chain in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

PubMed

Özkurt, Zübeyde Nur; Sucak, Gülsan Türköz; Akı, Şahika Zeynep; Yağcı, Münci; Haznedar, Rauf

2017-03-16

We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.

Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease

PubMed Central

Rosiñol, Laura; García-Sanz, Ramón; Lahuerta, Juan José; Hernández-García, Miguel; Granell, Miquel; de la Rubia, Javier; Oriol, Albert; Hernández-Ruiz, Belén; Rayón, Consuelo; Navarro, Isabel; García-Ruiz, Juan Carlos; Besalduch, Joan; Gardella, Santiago; Jiménez, Javier López; Díaz-Mediavilla, Joaquín; Alegre, Adrián; Miguel, Jesús San; Bladé, Joan

2012-01-01

Background Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease. Design and Methods In the Spanish Myeloma Group 2000 trial, 80 patients with primary refractory myeloma (49 with stable disease and 31 with progressive disease), i.e. who were refractory to initial chemotherapy, were scheduled for tandem transplants (double autologous transplant or a single autologous transplant followed by an allogeneic transplant). Patients with primary refractory disease included those who never achieved a minimal response (≥25% M-protein decrease) or better. Responses were assessed using the European Bone Marrow Transplant criteria. Results There were no significant differences in the rates of partial response or better between patients with stable or progressive disease. However, 38% of the patients with stable disease at the time of transplantation remained in a stable condition or achieved a minimal response after transplantation versus 7% in the group with progressive disease (P=0.0017) and the rate of early progression after transplantation was significantly higher among the group with progressive disease at the time of transplantation (22% versus 2%; P=0.0043). After a median follow-up of 6.6 years, the median survival after first transplant of the whole series was 2.3 years. Progression-free and overall survival from the first transplant were shorter in patients with progressive disease (0.6 versus 2.3 years, P=0.00004 and 1.1 versus 6 years, P=0.00002, respectively). Conclusions Our results show that patients with progressive refractory myeloma do not benefit from autologous transplantation, while patients with stable disease have an outcome comparable to those with chemosensitive disease. (ClinicalTrials.gov:NCT00560053) PMID:22058223

Label Review Training: Module 1: Label Basics, Page 21

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about types of labels.

Autologous tenocyte implantation into shoulder tendon pathology in an elite swimmer.

PubMed

Schwab, Laura M; Blanch, Peter; Young, Mark

2018-01-01

The use of novel bioengineer treatment techniques such as Autologous Tenocyte Implantation (ATI) have shown promising improvements in both pain ratings and functional outcomes in elbow, gluteal and shoulder tendon pathology. This case will review the injury timeline of ATI intervention in an elite male swimmer with subscapularis tendon pathology and investigate whether ATI has a concomitant healing effect associated with improved functional outcomes. A palmaris longus tendon biopsy was performed and cells were expanded by in-vitro culture. Autologous tenocytes were injected into the subscapularis site identified. Three blinded radiologists reported on pre and post shoulder MRIs using the same 3T MRI protocol. A validated rating scale for severity of tendinopathy (0-3) and degree of tear (0-3) was used and hand-held Dynamometry (HHD) strength was recorded. Independent blinded radiology review demonstrated a significant reduction in tear size and improved tendon morphology. IR strength on HHD returned to baseline strength levels post ATI (231-253N) 6 weeks post intervention. The athlete returned to full training (volume and intensity) pain free and international level competition at 4 months post ATI. An athlete who had previously undergone unsuccessful conservative management demonstrated significant improvement in function and in tendon morphology post intervention. Copyright © 2017 Elsevier Ltd. All rights reserved.

Renal Allograft Survival in Nonhuman Primates Infused With Donor Antigen-Pulsed Autologous Regulatory Dendritic Cells.

PubMed

Ezzelarab, M B; Raich-Regue, D; Lu, L; Zahorchak, A F; Perez-Gutierrez, A; Humar, A; Wijkstrom, M; Minervini, M; Wiseman, R W; Cooper, D K C; Morelli, A E; Thomson, A W

2017-06-01

Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg preloaded with cell membrane vesicles from allogeneic peripheral blood mononuclear cells induce T cell hyporesponsiveness to donor alloantigen (alloAg) in vitro. These donor alloAg-pulsed autologous DCreg (1.4-3.6 × 10 6 /kg) were administered intravenously, 1 day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 immunoglobulin [CTLA4] Ig) and tapered rapamycin. Prolongation of graft median survival time from 39.5 days (no DCreg infusion; n = 6 historical controls) and 29 days with control unpulsed DCreg (n = 2), to 56 days with donor Ag-pulsed DCreg (n = 5) was associated with evidence of modulated host CD4 + and CD8 + T cell responses to donor Ag and attenuation of systemic IL-17 production. Circulating anti-donor antibody (Ab) was not detected until CTLA4 Ig withdrawal. One monkey treated with donor Ag-pulsed DCreg rejected its graft in association with progressively elevated anti-donor Ab, 525 days posttransplant (160 days after withdrawal of immunosuppression). These findings indicate a modest but not statistically significant beneficial effect of donor Ag-pulsed autologous DCreg infusion on NHP graft survival when administered with a minimal immunosuppressive drug regimen. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Label Review Training: Module 1: Label Basics, Page 20

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This section focuses on supplemental labeling.

Label Review Training: Module 1: Label Basics, Page 22

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about what labels require review.

Label Review Training: Module 1: Label Basics, Page 19

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This section covers supplemental distributor labeling.

Ex-vivo transduced autologous skin fibroblasts expressing human Lim Mineralization Protein-3 efficiently form new bone in animal models

PubMed Central

Lattanzi, Wanda; Parrilla, Claudio; Fetoni, Annarita; Logroscino, Giandomenico; Straface, Giuseppe; Pecorini, Giovanni; Stigliano, Egidio; Tampieri, Anna; Bedini, Rossella; Pecci, Raffaella; Michetti, Fabrizio; Gambotto, Andrea; Robbins, Paul D.; Pola, Enrico

2012-01-01

Local gene transfer of the human LIM Mineralization Protein (LMP), a novel intracellular positive regulator of the osteoblast differentiation program, can induce efficient bone formation in rodents. In order to develop a clinically relevant gene therapy approach to facilitate bone healing, we have used primary dermal fibroblasts transduced ex vivo with Ad.LMP3 and seeded on an hydroxyapatite/collagen matrix prior to autologous implantation. Here we demonstrate that genetically modified autologous dermal fibroblasts expressing Ad.LMP-3 are able to induce ectopic bone formation following implantation of the matrix into the mouse triceps and paravertebral muscles. Moreover, implantation of the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size defect model results in efficient healing as determined by X-ray, histology and three dimensional micro computed tomography (3DμCT). These results demonstrate the effectiveness of the non-secreted intracellular osteogenic factor LMP-3, in inducing bone formation in vivo. Moreover, the utilization of autologous dermal fibroblasts implanted on a biomaterial represents a promising approach for possible future clinical applications aimed at inducing new bone formation. PMID:18633445

Long-term follow-up of autologous pericardial valved conduits.

PubMed

Schlichter, A J; Kreutzer, C; Mayorquim, R C; Simon, J L; Vazquez, H; Roman, M I; Kreutzer, G O

1996-07-01

The aim of this study was to evaluate the long-term results of the use of an autologous pericardial valved conduit in the outflow tract of the venous ventricle in congenital heart malformations. Fifty-one patients were followed up for a period of 12 to 120 months; 30 for more than 36 months and 13 for more than 72 months. All were evaluated clinically and by two-dimensional and Doppler echocardiography. Eight patients were recatheterized. Postoperative evaluation included serial measurement of pressure gradients and the conduit's diameter at the proximal, valvular, and distal levels. Reoperation because of stenosis was indicated when the gradient across the right ventricular outflow was greater than 50 mm Hg. The reoperation rate in relation with postoperative time, diameter of the autologous pericardial valved conduit at the time of implantation, and malformation was statistically analyzed. In 27 patients the conduit increased its diameter 1 to 7 mm. In 20 patients the diameter remained unchanged, whereas a reduction was noted in 4. Conduit survival free of reoperation for the whole group was 89.9% at 5 years. Conduit survival free of reoperation was 100% at 5 and 7 years for conduits larger than 16 mm at the time of implantation. It was 95% (standard deviation = 4.8%) at 5 years and 72.3% at 7 years for those 16 mm or less. For patients operated after January 1, 1986 (technical modification), conduit survival free of reoperation was 95.4% at 7 years postoperatively. These results compare favorably with those of other available conduits.

Label Review Training: Module 1: Label Basics, Page 18

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This section discusses the types of labels.

Label Review Training: Module 1: Label Basics, Page 26

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about mandatory and advisory label statements.

Label Review Training: Module 1: Label Basics, Page 15

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about the consequences of improper labeling.

Label Review Training: Module 1: Label Basics, Page 14

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about positive effects from proper labeling.

Parameters of Microcirculation in the Broad Ligament of the Uterus in Wistar Rats after Injection of Autologous Biomedical Cell Product.

PubMed

Dergacheva, T I; Lykov, A P; Shurlygina, A V; Starkova, E V; Poveshchenko, O V; Bondarenko, N A; Kim, I I; Tenditnik, M V; Borodin, Yu I; Konenkov, V I

2015-10-01

We studied the effects of autologous biomedical cell product (bone marrow multipotent mesenchymal stromal cells and their conditioned media) on the parameters of the microcirculatory bed in the broad ligament of the uterus of normal Wistar rats were studied. The parameters of microcirculation and lymph drainage in the broad ligament changed in opposite directions in response to injection of autologous biomedical cell product via different routes. This fact should be taken into consideration when prescribing cell therapy for inflammatory degenerative processes in the pelvic organs.

Label Review Training: Module 1: Label Basics, Page 24

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This page is about which labels require review.

Label Review Training: Module 1: Label Basics, Page 17

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. See an overview of the importance of labels.

Label Review Training: Module 1: Label Basics, Page 27

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. See examples of mandatory and advisory label statements.

Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens.

PubMed

Hessell, Ann J; Malherbe, Delphine C; Pissani, Franco; McBurney, Sean; Krebs, Shelly J; Gomes, Michelle; Pandey, Shilpi; Sutton, William F; Burwitz, Benjamin J; Gray, Matthew; Robins, Harlan; Park, Byung S; Sacha, Jonah B; LaBranche, Celia C; Fuller, Deborah H; Montefiori, David C; Stamatatos, Leonidas; Sather, D Noah; Haigwood, Nancy L

2016-04-01

Advancement in immunogen selection and vaccine design that will rapidly elicit a protective Ab response is considered critical for HIV vaccine protective efficacy. Vaccine-elicited Ab responses must therefore have the capacity to prevent infection by neutralization-resistant phenotypes of transmitted/founder (T/F) viruses that establish infection in humans. Most vaccine candidates to date have been ineffective at generating Abs that neutralize T/F or early variants. In this study, we report that coimmunizing rhesus macaques with HIV-1 gp160 DNA and gp140 trimeric protein selected from native envelope gene sequences (envs) induced neutralizing Abs against Tier 2 autologous viruses expressing cognate envelope (Env). The Env immunogens were selected from envs emerging during the earliest stages of neutralization breadth developing within the first 2 years of infection in two clade B-infected human subjects. Moreover, the IgG responses in macaques emulated the targeting to specific regions of Env known to be associated with autologous and heterologous neutralizing Abs developed within the human subjects. Furthermore, we measured increasing affinity of macaque polyclonal IgG responses over the course of the immunization regimen that correlated with Tier 1 neutralization. In addition, we report firm correlations between Tier 2 autologous neutralization and Tier 1 heterologous neutralization, as well as overall TZM-bl breadth scores. Additionally, the activation of Env-specific follicular helper CD4 T cells in lymphocytes isolated from inguinal lymph nodes of vaccinated macaques correlated with Tier 2 autologous neutralization. These results demonstrate the potential for native Env derived from subjects at the time of neutralization broadening as effective HIV vaccine elements. Copyright © 2016 by The American Association of Immunologists, Inc.

[Case of Rh (-) patient's right lobectomy of the liver with massive hemorrhage evading allogeneic blood transfusion by hemodilutional autologous blood transfusion].

PubMed

Nishimura, Masayuki; Takada, Norikazu; Hashiba, Eiji; Kimura, Futoshi; Kitayama, Masatou; Hashimoto, Hiroshi

2014-01-01

A 44-year-old man (ASA-PS 1) underwent right lobectomy of the liver under total intravenous anesthesia with propofol, remifentanil, ketamine and rocuronium. In order to evade allogeneic blood transfusion, 1,200 g of the patient's blood was taken and hemodilution was induced for autologous blood transfusion (HAT) after the induction of anesthesia. As intraoperative blood loss amounted to about 4,000 g, Hb level decreased from 13.6 to 6.2 g x dl(-1). However, as intraoperative hemodynamics was relatively stable with crystalloidal and colloidal transfusion with no ischemic change on ECG and no metabolic acidosis, autologous blood transfusion was withheld. After returning the autologous blood, Hb increased to 9.8 g x dl(-1). Any postoperative complications related to the low Hb level were not recognized. HAT is a useful method to evade or at least decrease the amount of allogeneic blood transfusion by anesthesiologists.

A Novel Method of Orbital Floor Reconstruction Using Virtual Planning, 3-Dimensional Printing, and Autologous Bone.

PubMed

Vehmeijer, Maarten; van Eijnatten, Maureen; Liberton, Niels; Wolff, Jan

2016-08-01

Fractures of the orbital floor are often a result of traffic accidents or interpersonal violence. To date, numerous materials and methods have been used to reconstruct the orbital floor. However, simple and cost-effective 3-dimensional (3D) printing technologies for the treatment of orbital floor fractures are still sought. This study describes a simple, precise, cost-effective method of treating orbital fractures using 3D printing technologies in combination with autologous bone. Enophthalmos and diplopia developed in a 64-year-old female patient with an orbital floor fracture. A virtual 3D model of the fracture site was generated from computed tomography images of the patient. The fracture was virtually closed using spline interpolation. Furthermore, a virtual individualized mold of the defect site was created, which was manufactured using an inkjet printer. The tangible mold was subsequently used during surgery to sculpture an individualized autologous orbital floor implant. Virtual reconstruction of the orbital floor and the resulting mold enhanced the overall accuracy and efficiency of the surgical procedure. The sculptured autologous orbital floor implant showed an excellent fit in vivo. The combination of virtual planning and 3D printing offers an accurate and cost-effective treatment method for orbital floor fractures. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Thermostability of Well-Ordered HIV Spikes Correlates with the Elicitation of Autologous Tier 2 Neutralizing Antibodies.

PubMed

Feng, Yu; Tran, Karen; Bale, Shridhar; Kumar, Shailendra; Guenaga, Javier; Wilson, Richard; de Val, Natalia; Arendt, Heather; DeStefano, Joanne; Ward, Andrew B; Wyatt, Richard T

2016-08-01

In the context of HIV vaccine design and development, HIV-1 spike mimetics displaying a range of stabilities were evaluated to determine whether more stable, well-ordered trimers would more efficiently elicit neutralizing antibodies. To begin, in vitro analysis of trimers derived from the cysteine-stabilized SOSIP platform or the uncleaved, covalently linked NFL platform were evaluated. These native-like trimers, derived from HIV subtypes A, B, and C, displayed a range of thermostabilities, and were "stress-tested" at varying temperatures as a prelude to in vivo immunogenicity. Analysis was performed both in the absence and in the presence of two different adjuvants. Since partial trimer degradation was detected at 37°C before or after formulation with adjuvant, we sought to remedy such an undesirable outcome. Cross-linking (fixing) of the well-ordered trimers with glutaraldehyde increased overall thermostability, maintenance of well-ordered trimer integrity without or with adjuvant, and increased resistance to solid phase-associated trimer unfolding. Immunization of unfixed and fixed well-ordered trimers into animals revealed that the elicited tier 2 autologous neutralizing activity correlated with overall trimer thermostability, or melting temperature (Tm). Glutaraldehyde fixation also led to higher tier 2 autologous neutralization titers. These results link retention of trimer quaternary packing with elicitation of tier 2 autologous neutralizing activity, providing important insights for HIV-1 vaccine design.

Label Review Training: Module 1: Label Basics, Page 23

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Lists types of labels that do not require review.

Rapid and automated processing of bone marrow grafts without Ficoll density gradient for transplantation of cryopreserved autologous or ABO-incompatible allogeneic bone marrow.

PubMed

Schanz, U; Gmür, J

1992-12-01

The growing number of BMTs has increased interest in safe and standardized in vitro bone marrow processing techniques. We describe our experience with a rapid automated method for the isolation of mononuclear cells (MNC) from large volumes of bone marrow using a Fenwal CS-3000 cell separator without employing density gradient materials. Forty bone marrow harvests with a mean volume of 1650 +/- 307 ml were processed. A mean of 75 +/- 34% (50 percentile range 54-94%) of the original MNCs were recovered in a volume of 200 ml with only 4 +/- 2% of the starting red blood cells (RBC). Removal of granulocytes, immature myeloid precursors and platelets proved to be sufficient to permit safe cryopreservation and successful autologous BMT (n = 25). Allogeneic BMT (n = 14, including three major ABO-incompatible) could be performed without additional manipulation. In both groups of patients timely and stable engraftment comparable to historical controls receiving Ficoll gradient processed autologous (n = 17) or unprocessed allogeneic BMT (n = 54) was observed. Moreover, 70 +/- 14% of the RBC could be recovered from the grafts. They were used for autologous RBC support of donors, rendering unnecessary autologous blood pre-donations.

Survival of Mexican children with acute myeloid leukaemia who received early intensification chemotherapy and an autologous transplant.

PubMed

Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Villegas, Octavio Martínez; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

2015-01-01

In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005-2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999-2004, was treated as Group A, but without the early intensified chemotherapy. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.

Autologous bone marrow Th cells can support multiple myeloma cell proliferation in vitro and in xenografted mice.

PubMed

Wang, D; Fløisand, Y; Myklebust, C V; Bürgler, S; Parente-Ribes, A; Hofgaard, P O; Bogen, B; Taskén, K; Tjønnfjord, G E; Schjesvold, F; Dalgaard, J; Tveita, A; Munthe, L A

2017-10-01

Multiple myeloma (MM) is a plasma cell malignancy where MM cell growth is supported by the bone marrow (BM) microenvironment with poorly defined cellular and molecular mechanisms. MM cells express CD40, a receptor known to activate autocrine secretion of cytokines and elicit proliferation. Activated T helper (Th) cells express CD40 ligand (CD40L) and BM Th cells are significantly increased in MM patients. We hypothesized that activated BM Th cells could support MM cell growth. We here found that activated autologous BM Th cells supported MM cell growth in a contact- and CD40L-dependent manner in vitro. MM cells had retained the ability to activate Th cells that reciprocated and stimulated MM cell proliferation. Autologous BM Th cells supported MM cell growth in xenografted mice and were found in close contact with MM cells. MM cells secreted chemokines that attracted Th cells, secretion was augmented by CD40-stimulation. Within 14 days of culture of whole BM aspirates in autologous serum, MM cells and Th cells mutually stimulated each other, and MM cells required Th cells for further expansion in vitro and in mice. The results suggest that Th cells may support the expansion of MM cells in patients.

Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy

PubMed Central

2012-01-01

Backgrounds We conducted a pilot study of the infusion of intravenous autologous cord blood (CB) in children with cerebral palsy (CP) to assess the safety and feasibility of the procedure as well as its potential efficacy in countering neurological impairment. Methods Patients diagnosed with CP were enrolled in this study if their parents had elected to bank their CB at birth. Cryopreserved CB units were thawed and infused intravenously over 10~20 minutes. We assessed potential efficacy over 6 months by brain magnetic resonance imaging (MRI)-diffusion tensor imaging (DTI), brain perfusion single-photon emission computed tomography (SPECT), and various evaluation tools for motor and cognitive functions. Results Twenty patients received autologous CB infusion and were evaluated. The types of CP were as follows: 11 quadriplegics, 6 hemiplegics, and 3 diplegics. Infusion was generally well-tolerated, although 5 patients experienced temporary nausea, hemoglobinuria, or urticaria during intravenous infusion. Diverse neurological domains improved in 5 patients (25%) as assessed with developmental evaluation tools as well as by fractional anisotropy values in brain MRI-DTI. The neurologic improvement occurred significantly in patients with diplegia or hemiplegia rather than quadriplegia. Conclusions Autologous CB infusion is safe and feasible, and has yielded potential benefits in children with CP. PMID:22443810

Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair.

PubMed

Hindle, Paul; Baily, James; Khan, Nusrat; Biant, Leela C; Simpson, A Hamish R; Péault, Bruno

2016-11-01

Previous research has indicated that purified perivascular stem cells (PSCs) have increased chondrogenic potential compared to conventional mesenchymal stem cells (MSCs) derived in culture. This study aimed to develop an autologous large animal model for PSC transplantation and to specifically determine if implanted cells are retained in articular cartilage defects. Immunohistochemistry and fluorescence-activated cell sorting were used to ascertain the reactivity of anti-human and anti-ovine antibodies, which were combined and used to identify and isolate pericytes (CD34 - CD45 - CD146 + ) and adventitial cells (CD34 + CD45 - CD146 - ). The purified cells demonstrated osteogenic, adipogenic, and chondrogenic potential in culture. Autologous ovine PSCs (oPSCs) were isolated, cultured, and efficiently transfected using a green fluorescence protein (GFP) encoding lentivirus. The cells were implanted into articular cartilage defects on the medial femoral condyle using hydrogel and collagen membranes. Four weeks following implantation, the condyle was explanted and confocal laser scanning microscopy demonstrated the presence of oPSCs in the defect repaired with the hydrogel. These data suggest the testability in a large animal of native MSC autologous grafting, thus avoiding possible biases associated with xenotransplantation. Such a setting will be used in priority for indications in orthopedics, at first to model articular cartilage repair.

[Distal Pancreatectomy with Autologous Fibrin Sealant - Implementation of an Established Concept of Tissue Sealing in Pancreatic Surgery].

PubMed

Luu, A M; Braumann, C; Belyaev, O; Janot, M; Uhl, W; Herzog, T

2016-12-01

Background: Postoperative pancreatic fistulas (POPF) remain a major concern after distal pancreatectomy. Irrespective of the technique to close the pancreatic remnant, pancreatic fistulas will occur in approximately 30 % of patients undergoing distal pancreatectomy. For the first time ever, autologous fibrin sealant (Vivostat®) was used to additionally seal the pancreatic remnant after a distal pancreatectomy. The aim was to analyse whether this changes the postoperative outcome. Patients/Material and Methods: In 2015, a technical case series was performed in 15 patients who underwent distal pancreatectomy. The pancreatic remnant was additionally sealed with autologous fibrin sealant (Vivostat®). Results: A postoperative pancreatic fistula (POPF) occurred in 5/15 patients (33 %). One patient had a POPF grade A (1/15, 6.7 %), whereas a POPF grade B occurred in 4/15 patients (26.7 %). 75 % (3/4) of the patients with a POPF grade B were sufficiently treated with antibiotics, whereas a CT-guided percutaneous drainage had to be placed only in one case. Conclusion: Autologous fibrin sealant is simple to apply and seems to be well tolerated. However, it does not seem to avoid the development of postoperative pancreatic fistulas after distal pancreatectomy. Georg Thieme Verlag KG Stuttgart · New York.

Patients' health beliefs and coping prior to autologous peripheral stem cell transplantation.

PubMed

Frick, E; Fegg, M J; Tyroller, M; Fischer, N; Bumeder, I

2007-03-01

The aim of this study was to determine the associations between health locus of control (LoC), causal attributions and coping in tumour patients prior to autologous peripheral blood stem cell transplantation. Patients completed the Questionnaire of Health Related Control Expectancies, the Questionnaire of Personal Illness Causes (QPIC), and the Freiburg Questionnaire of Coping with Illness. A total of 126 patients (45% women; 54% suffering from a multiple myeloma, 29% from non-Hodgkin lymphomas, and 17% from other malignancies) participated in the study. Cluster analysis yielded four LoC clusters: 'fatalistic external', 'powerful others', 'yeah-sayer' and 'double external'. Self-blaming QPIC items were positively correlated with depressive coping, and 'fate or destiny' attributions with religious coping (P<0.001). The highest scores were found for 'active coping' in the LoC clusters 'powerful others' and 'yeah-sayer'. External LoC and an active coping style prevail before undergoing autologous peripheral blood stem cell transplantation, whereas the depressive coping is less frequent, associated with self-blaming causal attributions. Health beliefs include causal and control attributions, which can improve or impair the patient's adjustment. A mixture between internal and external attributions seems to be most adaptive.

Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia

PubMed Central

Gribben, John G.; Zahrieh, David; Stephans, Katherine; Bartlett-Pandite, Lini; Alyea, Edwin P.; Fisher, David C.; Freedman, Arnold S.; Mauch, Peter; Schlossman, Robert; Sequist, Lecia V.; Soiffer, Robert J.; Marshall, Blossom; Neuberg, Donna; Ritz, Jerome; Nadler, Lee M.

2005-01-01

We report here on the long-term follow-up on 162 patients with high-risk chronic lymphocytic leukemia (CLL) who have undergone hematopoietic stem cell transplantation (SCT) at a single center from 1989 to 1999. Twenty-five patients with human leukocyte antigen (HLA)-matched sibling donors underwent T-cell-depleted allogeneic SCT, and 137 patients without HLA-matched sibling donors underwent autologous SCT. The 100-day mortality was 4% for both groups, but later morbidity and mortality were negatively affected on outcome. Progression-free survival was significantly longer following autologous than allogeneic SCT, but there was no difference in overall survival and no difference in the cumulative incidence of disease recurrence or deaths without recurrence between the 2 groups. At a median follow-up of 6.5 years there is no evidence of a plateau of progression-free survival. The majority of patients treated with donor lymphocyte infusions after relapse responded, demonstrating a significant graft-versus-leukemia effect in CLL. From these findings we have altered our approach for patients with high-risk CLL and are currently exploring the role of related and unrelated allogeneic SCT following reduced-intensity conditioning regimens. PMID:16131571

Autologous islet transplantation with remote islet isolation after pancreas resection for chronic pancreatitis.

PubMed

Tai, Denise S; Shen, Na; Szot, Gregory L; Posselt, Andrew; Feduska, Nicholas J; Habashy, Andrew; Clerkin, Barbara; Core, Erin; Busuttil, Ronald W; Hines, O Joe; Reber, Howard A; Lipshutz, Gerald S

2015-02-01

Autologous islet transplantation is an elegant and effective method for preserving euglycemia in patients undergoing near-total or total pancreatectomy for severe chronic pancreatitis. However, few centers worldwide perform this complex procedure, which requires interdisciplinary coordination and access to a sophisticated Food and Drug Administration-licensed islet-isolating facility. To investigate outcomes from a single institutional case series of near-total or total pancreatectomy and autologous islet transplantation using remote islet isolation. Retrospective cohort study between March 1, 2007, and December 31, 2013, at tertiary academic referral centers among 9 patients (age range, 13-47 years) with chronic pancreatitis and reduced quality of life after failed medical management. Pancreas resection, followed by transport to a remote facility for islet isolation using a modified Ricordi technique, with immediate transplantation via portal vein infusion. Islet yield, pain assessment, insulin requirement, costs, and transport time. Eight of nine patients had successful islet isolation after near-total or total pancreatectomy. Four of six patients with total pancreatectomy had islet yields exceeding 5000 islet equivalents per kilogram of body weight. At 2 months after surgery, all 9 patients had significantly reduced pain or were pain free. Of these patients, 2 did not require insulin, and 1 required low doses. The mean transport cost was $16,527, and the mean transport time was 3½ hours. Pancreatic resection with autologous islet transplantation for severe chronic pancreatitis is a safe and effective final alternative to ameliorate debilitating pain and to help prevent the development of surgical diabetes. Because many centers lack access to an islet-isolating facility, we describe our experience using a regional 2-center collaboration as a successful model to remotely isolate cells, with outcomes similar to those of larger case series.

Neoadjuvant Radiotherapy: Changing the Treatment Sequence to Allow Immediate Free Autologous Breast Reconstruction.

PubMed

Hughes, Kimberley; Neoh, Derek

2018-06-16

 Locally advanced breast cancer (LABC) is traditionally treated with a multimodal approach of chemotherapy, surgery, and postmastectomy radiotherapy (PMRT). The advantages of immediate breast reconstruction (IBR) are well described and include improved aesthetic outcomes, fewer surgical procedures, shorter treatment period, and a higher quality of life. However, this sequence makes immediate free autologous reconstruction more challenging as PMRT can have deleterious and unpredictable effects on the flap. We have reversed this treatment sequence with neoadjuvant chemotherapy and radiotherapy, followed by mastectomy and immediate free autologous reconstruction. To our knowledge, this is the first series to assess the outcomes of neoadjuvant radiotherapy on immediate free microvascular breast reconstruction.  A review of patients with LABC who underwent immediate free autologous breast reconstruction post neoadjuvant chemoradiotherapy between 2013 and 2017 was conducted. All reconstructions were performed by a single reconstructive team. The primary end points were flap failure and surgical complications. Secondary end points were pathological response rate and disease recurrence.  A total of 40 women with an average age of 48.1 (36-61) and average body mass index of 25.6 (18-37) were included. The most common choice of flap was immediate deep inferior epigastric perforator (DIEP, 31), followed by transverse or diagonal upper gracilis (5), muscle-sparing transversus abdominis (3), and stacked DIEP (1). Our major complication rate was 12.5% and minor complication 15%. There were no cases of local recurrence and only three cases (7.5%) of distant disease progression.  From our experience, this treatment sequence allows patients to have an immediate gold standard reconstruction without an increase in surgical morbidity. It affords the benefits of IBR without concern in delaying adjuvant therapy and appears to be safe from an oncological perspective. Thieme

Human Leucocyte Antigen Profile and Transmission of Mutans Streptococci in Mother-Child Pairs.

PubMed

Wallengren, Marie L; Hedström, Kristin; Zbroszczyk, Katarzyna; Hamberg, Kristina

2015-01-01

To investigate possible association between the transmission of mutans streptococci and sharing the immune system component Human Leucocyte Antigen (HLA) class II in mother-child pairs. Plaque samples from 43 mother-child pairs were cultivated and screened for mutans streptococci. In 14 pairs where both mother and child harboured the bacteria, the strains were genotyped by Random Amplified Polymorphic DNA and samples were run on PAGE gels. Analysis of genetic identity between mother and child strains was performed with help of software and Dice similarity index. The distribution of HLA of serogroup DR4 (HLA DR4) was studied in relation to maternal transmission and mutans streptococci colonisation in children. The study hypothesis was that in pairs where both mother and child were HLA DR4 positive, transmission of mutans streptococci was more likely. No correlation between the presence of HLA DR4 in mother and child and maternal transmission of mutans streptococci was established. However, the results showed no linkage between mutans streptococci colonisation and HLA DR 4. Of 15 children with mutans streptococci, 12 were HLA DR4 positive. The result suggests that presence of HLA DR4 could be a predisposing factor for colonisation with mutans streptococci in children.

Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.

PubMed

van Laar, Jacob M; Farge, Dominique; Sont, Jacob K; Naraghi, Kamran; Marjanovic, Zora; Larghero, Jérôme; Schuerwegh, Annemie J; Marijt, Erik W A; Vonk, Madelon C; Schattenberg, Anton V; Matucci-Cerinic, Marco; Voskuyl, Alexandre E; van de Loosdrecht, Arjan A; Daikeler, Thomas; Kötter, Ina; Schmalzing, Marc; Martin, Thierry; Lioure, Bruno; Weiner, Stefan M; Kreuter, Alexander; Deligny, Christophe; Durand, Jean-Marc; Emery, Paul; Machold, Klaus P; Sarrot-Reynauld, Francoise; Warnatz, Klaus; Adoue, Daniel F P; Constans, Joël; Tony, Hans-Peter; Del Papa, Nicoletta; Fassas, Athanasios; Himsel, Andrea; Launay, David; Lo Monaco, Andrea; Philippe, Pierre; Quéré, Isabelle; Rich, Éric; Westhovens, Rene; Griffiths, Bridget; Saccardi, Riccardo; van den Hoogen, Frank H; Fibbe, Willem E; Socié, Gérard; Gratwohl, Alois; Tyndall, Alan

2014-06-25

High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. HSCT vs intravenous pulse cyclophosphamide. The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year

Label Review Training: Module 1: Label Basics, Page 16

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about the importance of labels and the role in enforcement.

Defibrotide prevents the activation of macrovascular and microvascular endothelia caused by soluble factors released to blood by autologous hematopoietic stem cell transplantation.

PubMed

Palomo, Marta; Diaz-Ricart, Maribel; Rovira, Montserrat; Escolar, Ginés; Carreras, Enric

2011-04-01

Endothelial activation and damage occur in association with autologous hematopoietic stem cell transplantation (HSCT). Several of the early complications associated with HSCT seem to have a microvascular location. Through the present study, we have characterized the activation and damage of endothelial cells of both macro (HUVEC) and microvascular (HMEC) origin, occurring early after autologous HSCT, and the potential protective effect of defibrotide (DF). Sera samples from patients were collected before conditioning (Pre), at the time of transplantation (day 0), and at days 7, 14, and 21 after autologous HSCT. Changes in the expression of endothelial cell receptors at the surface, presence and reactivity of extracellular adhesive proteins, and the signaling pathways involved were analyzed. The expression of ICAM-1 at the cell surface increased progressively in both HUVEC and HMEC. However, a more prothrombotic profile was denoted for HMEC, in particular at the time of transplantation (day 0), reflecting the deleterious effect of the conditioning treatment on the endothelium, especially at a microvascular location. Interestingly, this observation correlated with a higher increase in the expression of both tissue factor and von Willebrand factor on the extracellular matrix, together with activation of intracellular p38 MAPK and Akt. Previous exposure and continuous incubation of cells with DF prevented the signs of activation and damage induced by the autologous sera. These observations corroborate that conditioning treatment in autologous HSCT induces a proinflammatory and a prothrombotic phenotype, especially at a microvascular location, and indicate that DF has protective antiinflammatory and antithrombotic effects in this setting. Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Clinical evaluations of complete autologous fibrin glue, produced by the CryoSeal® FS system, and polyglycolic acid sheets as wound coverings after oral surgery.

PubMed

Kouketsu, Atsumu; Nogami, Shinnosuke; Yamada-Fujiwara, Minami; Nagai, Hirokazu; Yamauchi, Kensuke; Mori, Shiro; Miyashita, Hitoshi; Kawai, Tadashi; Matsui, Aritsune; Kataoka, Yoshihiro; Satomi, Norihisa; Ezoe, Yushi; Abe, Satoko; Takeda, Yuri; Tone, Takeshi; Hirayama, Bunnichi; Kurobane, Tsuyoshi; Tashiro, Kazuki; Yanagisawa, Yuta; Takahashi, Tetsu

2017-09-01

The CryoSeal ® FS System has been recently introduced as an automated device for the production of complete fibrin glue from autologous plasma, rather than from pool allogenic or cattle blood, to prevent viral infection and allergic reaction. We evaluated the effectiveness of complete autologous fibrin glue and polyglycolic acid (PGA) sheet wound coverings in mucosa defect oral surgery. Postoperative pain, scar contracture, ingestion, tongue dyskinesia, and postoperative bleeding were evaluated in 12 patients who underwent oral (including the tongue) mucosa excision, and received a PGA sheet and an autologous fibrin glue covering. They were compared with 12 patients who received a PGA sheet and commercial allogenic fibrin glue. All cases in the complete autologous fibrin glue group demonstrated good wound healing without complications such as local infection or incomplete cure. All evaluated clinical measures in this group were similar or superior to the commercial allogenic fibrin glue group. Coagulation and adhesion quality achieved with this method was comparable to that with a PGA sheet and commercial fibrin glue. Covering oral surgery wounds with complete autologous fibrin glue produced by an automated device was convenient, safe, and reduced the risk of viral infection and allergic reaction associated with conventional techniques. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Lysis of autologous human macrophages by lymphokine-activated killer cells: interaction of effector cell and target cell conjugates analyzed by scanning electron microscopy.

PubMed

Streck, R J; Helinski, E H; Ovak, G M; Pauly, J L

1990-09-01

Lymphokine (i.e., interleukin 2; IL-2)-activated killer (LAK) cells derived from normal human blood are known to destroy human tumor target cells. Accordingly, immunotherapy modalities using IL-2, either alone or in combination with LAK cells, have been evaluated for eradicating metastatic cancer. In studies conducted to characterize receptors on LAK cell membrane ultrastructures, we observed that LAK cells kill autologous human monocyte-derived macrophages (M phi). In these experiments, peripheral blood mononuclear cells of a healthy adult donor were cultured to generate LAK cells and autologous non-adherent M phi. Thereafter, conjugates were prepared by incubating for 3 h autologous populations of LAK cells and M phi. Examination of the conjugates by scanning electron microscopy (SEM) identified LAK cell-mediated killing of M phi. Moreover, SEM analysis of the LAK cell membrane architecture identified microvilli-like ultrastructures that provided a physical bridge that joined together the LAK cell and M phi. The immunological mechanism(s) underling LAK cell killing of autologous M phi is not known; nevertheless, these conjugates will provide a useful model to study membrane receptors on ultrastructures that mediate the initial stages of cytolysis that include target cell recognition and cell-to-cell adhesion. The results of our observations and the findings of other investigators who have also demonstrated LAK cell killing of autologous normal human leukocytes are discussed in the context of the association of IL-2 and IL-2-activated killer cells with side effects observed in ongoing clinical trials and with autoimmune disorders.

Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo

PubMed Central

Wei, Xiaowei; Wang, Benjie; Wang, Wei; Kang, Kai; Xie, Hui; Liu, Baoyi; Zhang, Xiuzhi; Zhang, Jinsong; Yang, Zhenming

2016-01-01

Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum–host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing. PMID:26843518

Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse

DTIC Science & Technology

2016-07-01

from mesenchymal stem cells (MSCs) and to investigate the analgesic and anti- tolerance effects and the safety of CLCs in animal models. We have...had significant analgesic and robust anti-tolerance effects in both cellular and animal models. Our research has led to 5 poster presentations at...reprogramming, Pain management, Tolerance, Drug abuse, Cell cultures, Spinal transplantation of autologous stem cells, Animal behavioral tests 16. SECURITY

Regulatory challenges for autologous tissue engineered products on their way from bench to bedside in Europe.

PubMed

Ram-Liebig, Gouya; Bednarz, Juergen; Stuerzebecher, Burkard; Fahlenkamp, Dirk; Barbagli, Guido; Romano, Giuseppe; Balsmeyer, Ulf; Spiegeler, Maria-Elsa; Liebig, Soeren; Knispel, Helmut

2015-03-01

Since the late eighties of last century the high potential of tissue engineered products (TEP)s has been shown for the treatment of various diseases and many scientific publications appeared in this field. However, only few products reached the market since. Development of TEPs is a promising but owing to its novelty a very challenging task that requires experts in this still developing field as well as ample financial resources. This paper summarises relevant regulatory challenges during quality, preclinical and clinical development of autologous TEPs in Europe. Selected strategies on how to manage major issues are presented, together with some examples from the development of an autologous TEP for urethroplasty. Considering these aspects may help other investigators with potential strategies during the development of novel TEPs. Copyright © 2014 Elsevier B.V. All rights reserved.

The history of autologous fat graft use for prevention of cerebrospinal fluid rhinorrhea after transsphenoidal approaches.

PubMed

Ziu, Mateo; Jimenez, David F

2013-11-01

Presented herein is a review of the history of fat graft use in preventing iatrogenic cerebrospinal fluid (CSF) rhinorrhea after transsphenoidal surgery. Since the first transsphenoidal surgeries were described in the early 1900s, the techniques of sellar packing to prevent CSF leak have evolved. Kanavel, Halstead, and Cushing used bismuth- or iodine-soaked gauze. Under Dandy's influence, fascia lata was the first autologous material to be used for the repair and prevention of CSF rhinorrhea. The use of autologous fat graft for this purpose has only been reported in recent decades. Montgomery was the first to use abdominal fat to obliterate the middle ear cavity in 1964, and Collins reported the first transsphenoidal application of fat graft in 1973. Other reports by Kirchner, Tindall, and Wilson followed. Copyright © 2013. Published by Elsevier Inc.

The emergence and popularisation of autologous somatic cellular therapies in Australia: therapeutic innovation or regulatory failure?

PubMed

McLean, Alison K; Stewart, Cameron; Kerridge, Ian

2014-09-01

Private stem cell clinics throughout Australia are providing autologous stem cell therapies for a range of chronic and debilitating illnesses despite the lack of published literature to support the clinical application of these therapies. The Therapeutic Goods Administration has excluded autologous stem cell therapies from its regulatory domain leaving such therapies to be regulated by the same mechanisms that regulate research, such as the National Health and Medical Research Council Research Ethics Guidelines, and clinical practice, such as the Australian Health Practitioner Regulation Agency. However, the provision of these stem cell therapies does not follow the established pathways for legitimate medical advance--therapeutic innovation or research. The current regulatory framework is failing to achieve its aims of protecting vulnerable patients and ensuring the proper conduct of medical practitioners in the private stem cell industry.

Improved autologous cortical bone harvest and viability with 2Flute otologic burs.

PubMed

Roth, Adam A; Tang, Pei-Ciao; Ye, Michael J; Mohammad, Khalid S; Nelson, Rick F

2018-01-01

To determine if 2Flute (Stryker Corporation, Kalamazoo, MI) otologic burs improve the size, cellular content, and bone healing of autologous cortical bone grafts harvested during canal wall reconstruction (CWR) tympanomastoidectomy with mastoid obliteration. Institutional review board-approved prospective cohort study. Human autologous cortical bone chips were harvested using various burs (4 and 6 mm diameter; multiflute, and 2Flute [Stryker Corporation]) from patients undergoing CWR tympanomastoidectomy for the treatment of chronic otitis media with cholesteatoma. Bone chip size, cell counts, cellular gene expression, and new bone formation were quantified. Bone chips were significantly larger when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (113 ± 14 μm 2 vs. 66 ± 8 μm 2 ; P < 0.05) and 4 mm diameter (70 ± 8 μm 2 vs. 50 ± 3 μm 2 ; P < 0.05). After 2 weeks in culture, cell numbers were significantly higher when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (48.7 ± 3 vs. 31.8 ± 3 cells/μg bone; P < 0.05) and 4 mm diameter (27.6 ± 1.2 vs. 8.8 ± 1.2 cells/μg bone; P < 0.05). Bone-derived cells express osteoblast markers (alkaline phosphatase, osteocalcin). Cultured cells are able to form new bone in culture, and bone formation is facilitated by the presence of bone chips. Use of 2Flute (Stryker Corporation) otologic burs for human autologous cortical bone harvest results in more viable bone fragments, with larger bone chips and more osteoblasts. Future studies are needed to determine if this leads to improved bone healing. NA. Laryngoscope, 128:E41-E46, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Phase I (Safety) Study of Autologous Tolerogenic Dendritic Cells in Type 1 Diabetic Patients

PubMed Central

Giannoukakis, Nick; Phillips, Brett; Finegold, David; Harnaha, Jo; Trucco, Massimo

2011-01-01

OBJECTIVE The safety of dendritic cells to selectively suppress autoimmunity, especially in type 1 diabetes, has never been ascertained. We investigated the safety of autologous dendritic cells, stabilized into an immunosuppressive state, in established adult type 1 diabetic patients. RESEARCH DESIGN AND METHODS A randomized, double-blind, phase I study was conducted. A total of 10, otherwise generally healthy, insulin-requiring type 1 diabetic patients between 18 and 60 years of age, without any other known or suspected health conditions, received autologous dendritic cells, unmanipulated or engineered ex vivo toward an immunosuppressive state. Ten million cells were administered intradermally in the abdomen once every 2 weeks for a total of four administrations. The primary end point determined the proportion of patients with adverse events on the basis of the physician’s global assessment, hematology, biochemistry, and immune monitoring for a period of 12 months. RESULTS The dendritic cells were safely tolerated. There were no discernible adverse events in any patient throughout the study. Other than a significant increase in the frequency of peripheral B220+ CD11c− B cells, mainly seen in the recipients of engineered dendritic cells during the dendritic cell administration period, there were no statistically relevant differences in other immune populations or biochemical, hematological, and immune biomarkers compared with baseline. CONCLUSIONS Treatment with autologous dendritic cells, in a native state or directed ex vivo toward a tolerogenic immunosuppressive state, is safe and well tolerated. Dendritic cells upregulated the frequency of a potentially beneficial B220+ CD11c− B-cell population, at least in type 1 diabetes autoimmunity. PMID:21680720

Measuring the labeling efficiency of pseudocontinuous arterial spin labeling.

PubMed

Chen, Zhensen; Zhang, Xingxing; Yuan, Chun; Zhao, Xihai; van Osch, Matthias J P

2017-05-01

Optimization and validation of a sequence for measuring the labeling efficiency of pseudocontinuous arterial spin labeling (pCASL) perfusion MRI. The proposed sequence consists of a labeling module and a single slice Look-Locker echo planar imaging readout. A model-based algorithm was used to calculate labeling efficiency from the signal acquired from the main brain-feeding arteries. Stability of the labeling efficiency measurement was evaluated with regard to the use of cardiac triggering, flow compensation and vein signal suppression. Accuracy of the measurement was assessed by comparing the measured labeling efficiency to mean brain pCASL signal intensity over a wide range of flip angles as applied in the pCASL labeling. Simulations show that the proposed algorithm can effectively calculate labeling efficiency when correcting for T1 relaxation of the blood spins. Use of cardiac triggering and vein signal suppression improved stability of the labeling efficiency measurement, while flow compensation resulted in little improvement. The measured labeling efficiency was found to be linearly (R = 0.973; P < 0.001) related to brain pCASL signal intensity over a wide range of pCASL flip angles. The optimized labeling efficiency sequence provides robust artery-specific labeling efficiency measurement within a short acquisition time (∼30 s), thereby enabling improved accuracy of pCASL CBF quantification. Magn Reson Med 77:1841-1852, 2017. © 2016 International Society for Magnetic Resonance in Medicine Magn Reson Med 77:1841-1852, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Intrapleural instillation of autologous blood for persistent air leak in spontaneous pneumothorax in patients with advanced chronic obstructive pulmonary disease.

PubMed

Cao, Guo qiang; Kang, Jun; Wang, Fangwen; Wang, Hucheng

2012-05-01

We evaluated the safety and efficacy of increasing doses of autologous blood patch pleurodesis in treating persistent air leaks in patients with advanced chronic obstructive pulmonary disease (COPD). Forty-four patients with COPD and spontaneous pneumothorax (SP) on the 7th day after intercostal tube drainage were randomly assigned to 4 groups, with 11 patients in each group. Groups A, B, and C were given increasing doses of autologous blood--ie, 0.5 mL/kg, 1 mL/kg, 2 mL/kg, respectively--whereas group D was given 1 mL/kg normal saline only. The procedure was repeated if the air leak persisted on postoperative days 9 and 11. Patients in group D crossed over and received autologous blood as in group B if the air leak was still present on the 13th postoperative day. No patient died in the study. The air leak was sealed by the 13th postoperative day only in patients with air leaks smaller than size 3. Air leaks were classified as 0 to 3 [12], ie, size 0=no air leak; size 1=air leak on vigorous coughing only; size 2=small continuous air leak on gentle respiration; and size 3=large continuous air leak on gentle respiration. The success rates by the 13th postoperative day in groups A, B, C, and D were 27%, 82%, 82%, and 9%, respectively. The success rate (82%) was significantly higher in groups B and C than in group A (p=0.003) and D (p>0.01). Using autologous blood to treat secondary spontaneous pneumothorax (SSP) in patients with advanced COPD is easy, safe, and effective. The dose of blood required for autologous blood patch pleurodesis should be dependent on the body weight, and 1 mL/kg blood may be efficient. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Autologous Mesenchymal Stem Cell and Islet Cotransplantation: Safety and Efficacy.

PubMed

Wang, Hongjun; Strange, Charlie; Nietert, Paul J; Wang, Jingjing; Turnbull, Taylor L; Cloud, Colleen; Owczarski, Stefanie; Shuford, Betsy; Duke, Tara; Gilkeson, Gary; Luttrell, Louis; Hermayer, Kathie; Fernandes, Jyotika; Adams, David B; Morgan, Katherine A

2018-01-01

Islet engraftment after transplantation is impaired by high rates of islet/β cell death caused by cellular stressors and poor graft vascularization. We studied whether cotransplantation of ex vivo expanded autologous bone marrow-derived mesenchymal stem cells (MSCs) with islets is safe and beneficial in chronic pancreatitis patients undergoing total pancreatectomy with islet autotransplantation. MSCs were harvested from the bone marrow of three islet autotransplantation patients and expanded at our current Good Manufacturing Practices (cGMP) facility. On the day of islet transplantation, an average dose of 20.0 ± 2.6 ×10 6 MSCs was infused with islets via the portal vein. Adverse events and glycemic control at baseline, 6, and 12 months after transplantation were compared with data from 101 historical control patients. No adverse events directly related to the MSC infusions were observed. MSC patients required lower amounts of insulin during the peritransplantation period (p = .02 vs. controls) and had lower 12-month fasting blood glucose levels (p = .02 vs. controls), smaller C-peptide declines over 6 months (p = .01 vs. controls), and better quality of life compared with controls. In conclusion, our pilot study demonstrates that autologous MSC and islet cotransplantation may be a safe and potential strategy to improve islet engraftment after transplantation. (Clinicaltrials.gov registration number: NCT02384018). Stem Cells Translational Medicine 2018;7:11-19. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Autologous islet transplantation: challenges and lessons.

PubMed

Dunn, Ty B; Wilhelm, Joshua J; Bellin, Melena D; Pruett, Timothy L

2017-08-01

Human islet isolation and autotransplantation [autologous islet transplant (AUTX)] is performed to prevent or ameliorate brittle diabetes after total pancreatectomy performed for benign disease. The success or failure of the transplant can be associated with a profound impact on the individual's quality of life and even survival. AUTX offers unique insights into the effects of pancreas quality, islet number, isolation technique and alternate site engraftment on transplant efficacy. Herein, we review islet isolation with a focus on potential pathways to further optimize the endocrine outcome of AUTX, and compare and contrast differences in islet processing for AUTX and allotransplantation (allogeneic islet transplant). New knowledge of human islet biology and issues surrounding the engraftment process offer opportunities for innovative approaches toward optimizing islet cell transplantation. Improving the rate and durability of insulin independence in the often-times marginal dose model of AUTX may provide new insight toward improving the efficiency and durability of single donor islet (allogeneic islet transplant).

Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model

PubMed Central

Ono, Mitsuaki; Oshima, Masamitsu; Ogawa, Miho; Sonoyama, Wataru; Hara, Emilio Satoshi; Oida, Yasutaka; Shinkawa, Shigehiko; Nakajima, Ryu; Mine, Atsushi; Hayano, Satoru; Fukumoto, Satoshi; Kasugai, Shohei; Yamaguchi, Akira; Tsuji, Takashi; Kuboki, Takuo

2017-01-01

Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model. Herein, we demonstrate functional tooth restoration through the autologous transplantation of bioengineered tooth germ in a postnatal canine model. The bioengineered tooth, which was reconstructed using permanent tooth germ cells, erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of a natural tooth. This study represents a substantial advancement in whole-organ replacement therapy through the transplantation of bioengineered organ germ as a practical model for future clinical regenerative medicine. PMID:28300208

Autologous bone graft versus demineralized bone matrix in internal fixation of ununited long bones.

PubMed

Pieske, Oliver; Wittmann, Alexandra; Zaspel, Johannes; Löffler, Thomas; Rubenbauer, Bianka; Trentzsch, Heiko; Piltz, Stefan

2009-12-15

Non-unions are severe complications in orthopaedic trauma care and occur in 10% of all fractures. The golden standard for the treatment of ununited fractures includes open reduction and internal fixation (ORIF) as well as augmentation with autologous-bone-grafting. However, there is morbidity associated with the bone-graft donor site and some patients offer limited quantity or quality of autologous-bone graft material. Since allogene bone-grafts are introduced on the market, this comparative study aims to evaluate healing characteristics of ununited bones treated with ORIF combined with either iliac-crest-autologous-bone-grafting (ICABG) or demineralized-bone-matrix (DBM). From 2000 to 2006 out of sixty-two consecutive patients with non-unions presenting at our Level I Trauma Center, twenty patients had ununited diaphyseal fractures of long bones and were treated by ORIF combined either by ICABG- (n = 10) or DBM-augmentation (n = 10). At the time of index-operation, patients of the DBM-group had a higher level of comorbidity (ASA-value: p = 0.014). Mean duration of follow-up was 56.6 months (ICABG-group) and 41.2 months (DBM-group). All patients were clinically and radiographically assessed and adverse effects related to bone grafting were documented. The results showed that two non-unions augmented with ICABG failed osseous healing (20%) whereas all non-unions grafted by DBM showed successful consolidation during the first year after the index operation (p = 0.146). No early complications were documented in both groups but two patients of the ICABG-group suffered long-term problems at the donor site (20%) (p = 0.146). Pain intensity were comparable in both groups (p = 0.326). However, patients treated with DBM were more satisfied with the surgical procedure (p = 0.031). With the use of DBM, the costs for augmentation of the non-union-site are more expensive compared to ICABG (calculated difference: 160 euro/case). Nevertheless, this study demonstrated that the

Autologous mesenchymal stem cells or meniscal cells: what is the best cell source for regenerative meniscus treatment in an early osteoarthritis situation?

PubMed

Zellner, Johannes; Pattappa, Girish; Koch, Matthias; Lang, Siegmund; Weber, Johannes; Pfeifer, Christian G; Mueller, Michael B; Kujat, Richard; Nerlich, Michael; Angele, Peter

2017-10-10

Treatment of meniscus tears within the avascular region represents a significant challenge, particularly in a situation of early osteoarthritis. Cell-based tissue engineering approaches have shown promising results. However, studies have not found a consensus on the appropriate autologous cell source in a clinical situation, specifically in a challenging degenerative environment. The present study sought to evaluate the appropriate cell source for autologous meniscal repair in a demanding setting of early osteoarthritis. A rabbit model was used to test autologous meniscal repair. Bone marrow and medial menisci were harvested 4 weeks prior to surgery. Bone marrow-derived mesenchymal stem cells (MSCs) and meniscal cells were isolated, expanded, and seeded onto collagen-hyaluronan scaffolds before implantation. A punch defect model was performed on the lateral meniscus and then a cell-seeded scaffold was press-fit into the defect. Following 6 or 12 weeks, gross joint morphology and OARSI grade were assessed, and menisci were harvested for macroscopic, histological, and immunohistochemical evaluation using a validated meniscus scoring system. In conjunction, human meniscal cells isolated from non-repairable bucket handle tears and human MSCs were expanded and, using the pellet culture model, assessed for their meniscus-like potential in a translational setting through collagen type I and II immunostaining, collagen type II enzyme-linked immunosorbent assay (ELISA), and gene expression analysis. After resections of the medial menisci, all knees showed early osteoarthritic changes (average OARSI grade 3.1). However, successful repair of meniscus punch defects was performed using either meniscal cells or MSCs. Gross joint assessment demonstrated donor site morbidity for meniscal cell treatment. Furthermore, human MSCs had significantly increased collagen type II gene expression and production compared to meniscal cells (p < 0.05). The regenerative potential of the

[Current Perceptions of Lipofilling on the Basis of the New Guideline on "Autologous Fat Grafting"].

PubMed

Prantl, L; Rennekampff, H O; Giunta, R E; Harder, Y; von Heimburg, D; Heine, N; Herold, C; Kneser, U; Lampert, F; Machens, H G; Mirastschijski, U; Müller, D; Pallua, N; Schantz, T; Schönborn, A; Ueberreiter, K; Witzel, C H; Bull, G; Rezek, D; Sattler, G; Vogt, P M; Horch, R E

2016-12-01

Introduction: Autologous fat transfer has recently become an increasingly popular surgical procedure and comprises harvesting, processing and transplantation of adipose tissue, as well as professional follow-up care. This method, as a surgical procedure, can be utilised for trauma-, disease- or age-related soft tissue volume deficits and soft tissue augmentation. As usage is increasing, but the variables of fat harvest, specific indications and fashion of fat transfer are poorly defined, there is a great demand for development of a guideline in the field of reconstructive and aesthetic surgery. Methods: All relevant points were discussed within the scope of a consensus conference including a nominal group process of all societies involved in the procedure and ratified with a strong consensus (>95%). Literature from the standard medical databases over the last 10 years was retrieved, studied and specific guidelines were concluded. Results: Consensus was achieved among all professionals involved on the following points: 1. definition 2. indication/contraindication, 3. preoperative measures 4. donor sites 5. techniques of processing 6. transplantation 7. follow-up care 8. storage 9. efficacy 10. documentation 11. evaluation of patient safety. Conclusion: Definite indications and professional expertise are paramount for autologous fat tissue transfer. Successful transfers are based on the use of correct methods as well as specific instruments and materials. Autologous adipose tissue transplantation is considered to be a safe procedure in reconstructive and aesthetic surgery, due to the low rate of postoperative complications and sequelae. © Georg Thieme Verlag KG Stuttgart · New York.

Comparison between Conventional Mechanical Fixation and Use of Autologous Platelet Rich Plasma (PRP) in Wound Beds Prior to Resurfacing with Split Thickness Skin Graft.

PubMed

P Waiker, Veena; Shivalingappa, Shanthakumar

2015-01-01

Platelet rich plasma is known for its hemostatic, adhesive and healing properties in view of the multiple growth factors released from the platelets to the site of wound. The primary objective of this study was to use autologous platelet rich plasma (PRP) in wound beds for anchorage of skin grafts instead of conventional methods like sutures, staplers or glue. In a single center based randomized controlled prospective study of nine months duration, 200 patients with wounds were divided into two equal groups. Autologous PRP was applied on wound beds in PRP group and conventional methods like staples/sutures used to anchor the skin grafts in a control group. Instant graft adherence to wound bed was statistically significant in the PRP group. Time of first post-graft inspection was delayed, and hematoma, graft edema, discharge from graft site, frequency of dressings and duration of stay in plastic surgery unit were significantly less in the PRP group. Autologous PRP ensured instant skin graft adherence to wound bed in comparison to conventional methods of anchorage. Hence, we recommend the use of autologous PRP routinely on wounds prior to resurfacing to ensure the benefits of early healing.

The Chondrogenic Induction Potential for Bone Marrow-Derived Stem Cells between Autologous Platelet-Rich Plasma and Common Chondrogenic Induction Agents: A Preliminary Comparative Study.

PubMed

Wang, Shan-Zheng; Chang, Qing; Kong, Xiang-Fei; Wang, Chen

2015-01-01

The interests in platelet-rich plasma (PRP) and their application in stem cell therapy have contributed to a better understanding of the basic biology of the prochondrogenesis effect on bone marrow-derived stem cells (BMSCs). We aimed at comparing the effect of autologous PRP with common chondrogenic induction agents (CCIAs) on the chondrogenic differentiation of BMSCs. Rabbit BMSCs were isolated and characterized by flow cytometry and differentiated towards adipocytes and osteoblasts. The chondrogenic response of BMSCs to autologous PRP and CCIAs which included transforming growth factor-β1 (TGF-β1), dexamethasone (DEX), and vitamin C (Vc) was examined by cell pellet culture. The isolated BMSCs after two passages highly expressed CD29 and CD44 but minimally expressed CD45. The osteogenic and adipogenic differentiation potentials of the isolated BMSCs were also confirmed. Compared with common CCIAs, autologous PRP significantly upregulated the chondrogenic related gene expression, including Col-2, AGC, and Sox-9. Osteogenic related gene expression, including Col-1 and OCN, was not of statistical significance between these two groups. Thus, our data shows that, compared with common chondrogenic induction agents, autologous PRP can be more effective in promoting the chondrogenesis of BMSCs.

Comparison of long-term voice outcomes after vocal fold augmentation using autologous fat injection by direct microlaryngoscopy versus office-based calcium hydroxylapatite injection.

PubMed

Zeleník, Karol; Walderová, Radana; Kučová, Hana; Jančatová, Debora; Komínek, Pavel

2017-08-01

The objective is to compare the long-term voice outcomes of vocal fold augmentation (VFA) using autologous fat injection via direct microlaryngoscopy versus office-based calcium hydroxylapatite (CaHA) injection. Patients with glottal insufficiency and a gap no greater than 3 mm caused by unilateral vocal fold paralysis or vocal fold atrophy were prospectively recruited to the study from September 2012 to September 2015. From September 2012 to May 2014, VFA was only performed using autologous fat via direct microlaryngoscopy under general anesthesia (N = 14). From May 2014 to September 2015, VFA was performed as an office-based procedure using a transoral approach to inject CaHA (N = 17). Videolaryngostroboscopic evaluation, subjective satisfaction with voice, voice handicap index (VHI), and maximal phonation time (MPT) were analyzed pre-injection and 12 months after VFA. A total of 31 patients were analyzed. One year after VFA, 67.8% of the patients were satisfied with their voice, with no significant difference between groups (P = 0.247). The mean improvement in VHI in the autologous fat group was 31.6 ± 16.82 versus 35 ± 27.24 in the CaHA group (P = 0.664). MPT improvement was also similar in the two groups: 5.5 ± 2.52 for the autologous fat group versus 6.0 ± 3.98 for the CaHA group (P = 0.823). Both autologous fat injection via direct microlaryngoscopy and office-based CaHA injection have good long-term results. There were no differences in the treatment results of the two procedures 1 year after injection.

Anterior debridement and fusion followed by posterior pedicle screw fixation in pyogenic spondylodiscitis: autologous iliac bone strut versus cage.

PubMed

Pee, Yong Hun; Park, Jong Dae; Choi, Young-Geun; Lee, Sang-Ho

2008-05-01

An anterior approach for debridement and fusion with autologous bone graft has been recommended as the gold standard for surgical treatment of pyogenic spondylodiscitis. The use of anterior foreign body implants at the site of active infection is still a challenging procedure for spine surgeons. Several authors have recently introduced anterior grafting with titanium mesh cages instead of autologous bone strut in the treatment of spondylodiscitis. The authors present their experience of anterior fusion with 3 types of cages followed by posterior pedicle screw fixation. They also compare their results with the use of autologous iliac bone strut. The authors retrospectively reviewed the cases of 60 patients with pyogenic spondylodiscitis treated by anterior debridement between January 2003 and April 2005. Fusion using either cages or iliac bone struts was performed during the same course of anesthesia followed by posterior fixation. Twenty-three patients underwent fusion with autologous iliac bone strut, and 37 patients underwent fusion with 1 of the 3 types of cages. The infections resolved in all patients, as noted by normalization of their erythrocyte sedimentation rates and C-reactive protein levels. Patients in both groups were evaluated in terms of their preoperative and postoperative clinical and imaging findings. Single-stage anterior debridement and cage fusion followed by posterior pedicle screw fixation can be effective in the treatment of pyogenic spondylodiscitis. There was no difference in clinical and imaging outcomes between the strut group and cage group except for the subsidence rate. The subsidence rate was higher in the strut group than in the cage group. The duration until subsidence was also shorter in the strut group than in the cage group.

Ten-year follow-up of pediatric patients with non-Hodgkin lymphoma treated with allogeneic or autologous stem cell transplantation.

PubMed

Giulino-Roth, Lisa; Ricafort, Rosanna; Kernan, Nancy A; Small, Trudy N; Trippett, Tanya M; Steinherz, Peter G; Prockop, Susan E; Scaradavou, Andromachi; Chiu, Michelle; O'Reilly, Richard J; Boulad, Farid

2013-12-01

Autologous or allogeneic hematopoietic stem cell transplant (SCT) is often considered in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) but there are limited data on the use of SCT for the treatment of NHL in the pediatric setting. To evaluate the role of SCT for children with NHL, we reviewed 36 consecutive pediatric patients with NHL who underwent an allogeneic (n = 21) or autologous (n = 15) SCT at our institution between 1982 and 2004. Pathologic classification included: lymphoblastic lymphoma (n = 12), Burkitt lymphoma (BL) (n = 5), diffuse large B-cell lymphoma (n = 4), anaplastic large cell lymphoma (ALCL) (n = 13), peripheral T cell lymphoma (n = 1), and undifferentiated NHL (n = 1). Donor source for allogeneic-SCT recipients was an HLA-matched related donor (n = 15), a matched unrelated donor (n = 4), or a mismatched donor (related n = 1; unrelated n = 1). Twenty-eight patients (78%) had chemotherapy responsive disease at the time of transplant (either CR or PR). Overall survival (OS) and disease-free survival (DFS) were 55% and 53% with a median follow-up of 9.75 years. Outcomes were similar in patients receiving autologous and allogeneic-SCT (DFS 53% in both groups). Patients with ALCL had a DFS of 76.9%. In contrast, of five patients transplanted for BL, none survived. DFS among patients with chemotherapy sensitive disease was 61%, compared with 25% among patients with relapsed/refractory disease (P = 0.019). Allogeneic and autologous SCT offer the prospect of durable, disease-free survival for a significant proportion of pediatric patients with relapsed or refractory NHL. Survival is superior among patients with chemotherapy sensitive disease. © 2013 Wiley Periodicals, Inc.

Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo.

PubMed

Wei, Xiaowei; Zhao, Dewei; Wang, Benjie; Wang, Wei; Kang, Kai; Xie, Hui; Liu, Baoyi; Zhang, Xiuzhi; Zhang, Jinsong; Yang, Zhenming

2016-03-01

Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum-host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing. © 2016 by the Society for Experimental Biology and Medicine.

Validated Outcomes in the Grafting of Autologous Fat to the Breast: The VOGUE Study. Development of a Core Outcome Set for Research and Audit.

PubMed

Agha, Riaz A; Pidgeon, Thomas E; Borrelli, Mimi R; Dowlut, Naeem; Orkar, Ter-Er K; Ahmed, Maziyah; Pujji, Ojas; Orgill, Dennis P

2018-05-01

Autologous fat grafting is an important part of the reconstructive surgeon's toolbox when treating women affected by breast cancer and subsequent tumor extirpation. The debate over safety and efficacy of autologous fat grafting continues within the literature. However, work performed by the authors' group has shown significant heterogeneity in outcome reporting. Core outcome sets have been shown to reduce heterogeneity in outcome reporting. The authors' goal was to develop a core outcome set for autologous fat grafting in breast reconstruction. The authors published their protocol a priori. A Delphi consensus exercise among key stakeholders was conducted using a list of outcomes generated from their previous work. These outcomes were divided into six domains: oncologic, clinical, aesthetic and functional, patient-reported, process, and radiologic. In the first round, 55 of 78 participants (71 percent) completed the Delphi consensus exercise. Consensus was reached on nine of the 13 outcomes. The clarity of the results and lack of additional suggested outcomes deemed further rounds to be unnecessary. The VOGUE Study has led to the development of a much-needed core outcome set in the active research front and clinical area of autologous fat grafting. The authors hope that clinicians will use this core outcome set to audit their practice, and that researchers will implement these outcomes in their study design and reporting of autologous fat grafting outcomes. The authors encourage journals and surgical societies to endorse and encourage use of this core outcome set to help refine the scientific quality of the debate, the discourse, and the literature. Therapeutic, V.

Combination of BMP-2-releasing gelatin/β-TCP sponges with autologous bone marrow for bone regeneration of X-ray-irradiated rabbit ulnar defects.

PubMed

Yamamoto, Masaya; Hokugo, Akishige; Takahashi, Yoshitake; Nakano, Takayoshi; Hiraoka, Masahiro; Tabata, Yasuhiko

2015-07-01

The objective of this study is to evaluate the feasibility of gelatin sponges incorporating β-tricalcium phosphate (β-TCP) granules (gelatin/β-TCP sponges) to enhance bone regeneration at a segmental ulnar defect of rabbits with X-ray irradiation. After X-ray irradiation of the ulnar bone, segmental critical-sized defects of 20-mm length were created, and bone morphogenetic protein-2 (BMP-2)-releasing gelatin/β-TCP sponges with or without autologous bone marrow were applied to the defects to evaluate bone regeneration. Both gelatin/β-TCP sponges containing autologous bone marrow and BMP-2-releasing sponges enhanced bone regeneration at the ulna defect to a significantly greater extent than the empty sponges (control). However, in the X-ray-irradiated bone, the bone regeneration either by autologous bone marrow or BMP-2 was inhibited. When combined with autologous bone marrow, the BMP-2 exhibited significantly high osteoinductivity, irrespective of the X-ray irradiation. The bone mineral content at the ulna defect was similar to that of the intact bone. It is concluded that the combination of bone marrow with the BMP-2-releasing gelatin/β-TCP sponge is a promising technique to induce bone regeneration at segmental bone defects after X-ray irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Protocol for obtaining platelet-rich plasma (PRP), platelet-poor plasma (PPP), and thrombin for autologous use.

PubMed

Franco, Diogo; Franco, Talita; Schettino, Angélica Maria; Filho, João Medeiros Tavares; Vendramin, Fabiel Spani

2012-10-01

Plasma has been widely studied and used in many different situations to speed up healing with better tissue adherence and hemostasis. Research projects are now attempting to isolate platelet-rich plasma (PRP) and platelet-poor plasma (PPP), making better use of their properties, particularly during operations and for wounds that are slow to heal. In view of the wide diversity of industrial machines and extraction protocols, together with the variety of industrially produced biologic glues, this article suggests an option for obtaining PRP, PPP, and human thrombin for autologous use. A way of obtaining PRP, PPP, and thrombin is reproduced through a protocol defined and established by the authors. Autologous thrombin and plasma were obtained through the collection and successive centrifugation of ten whole blood samples, until the desired hemocomponents were isolated, followed by quantitative and qualitative analyses of the elements obtained. The mean platelet concentration obtained was 6.03 × 10(8) platelets/ml, with a mean thrombin concentration of 33.54 nM, both values compatible with reports in the literature when different protocols are applied. The protocol described is a good option for the preparation and application of PRP, PPP, and autologous thrombin, particularly as they can be obtained simultaneously, eliminating the possibilities of viral contamination and allergic reactions. Moreover, the cost of this procedure is low, it is easy to perform, and replicable. This journal requires that authors assign a level of evidence to each article.

G-spot augmentation with autologous fat transplantation.

PubMed

Herold, Christian; Motamedi, Melodi; Hartmann, Uwe; Allert, Sixtus

2015-01-01

Lipofilling for G-spot augmentation is appealing because long-term persistence of the fat is expected to be very good. We report the case of a 29-year-old patient who requested G-spot augmentation to enhance sexual sensation. Autologous fat (8 cc) that was harvested from the trochanteric area was injected. Although there are few published data acknowledging the presence of the G-spot, the patient was satisfied with the procedure and no side effects occurred. Nevertheless, evaluation with standard questionnaires, such as Fragebogen zur Lebenszufriedenheit (FLZ) and Kurzfragebogen für sexuelle Probleme (KFSP-F), did not indicate the positive effects on subjective well-being and sexual parameters of a surgical G-spot augmentation. Studies comprising a larger series of patients are required before substantiated recommendations regarding the benefits and risks of this procedure will be possible.

Clinical observation of the application of autologous peripheral blood stem cell transplantation for the treatment of diabetic foot gangrene

PubMed Central

XU, SHI-MIN; LIANG, TING

2016-01-01

The aim of the present study was to investigate the optimal mobilization plan in autologous peripheral blood stem cell transplantation for the treatment of diabetic foot and to observe its clinical curative effect. A total of 127 patients with diabetic foot were treated with different doses of granulocyte colony stimulating factor (G-CSF) to mobilize their hematopoietic stem cells. Subsequently, the extracted stem cell suspension was injected into the ischemic lower extremities along the blood vessels in the areas presenting with pathological changes. Following the treatment, the intermittent claudication distance, skin temperature, ankle brachial index and pain scores of the patients were evaluated. In addition, the associations among the mobilization time, doses and peripheral blood CD34+ level were analyzed. The collection efficiency of the stem cells was associated with the dose of G-CSF and the mobilization time. Following the injection of the autologous peripheral blood stem cell suspension, the ischemic area of the patients was improved significantly. In conclusion, autologous peripheral blood stem cell transplantation can promote the establishment of collateral circulation in patients with diabetic foot, and the optimal time for gathering stem cells is closely correlated with the peripheral blood CD34+ level. PMID:26889255

Blood management and transfusion strategies in 600 patients undergoing total joint arthroplasty: an analysis of pre-operative autologous blood donation.

PubMed

Perazzo, Paolo; Viganò, Marco; De Girolamo, Laura; Verde, Francesco; Vinci, Anna; Banfi, Giuseppe; Romagnoli, Sergio

2013-07-01

Blood loss during total joint arthroplasty strongly influences the time to recover after surgery and the quality of the recovery. Blood conservation strategies such as pre-operative autologous blood donation and post-operative cell salvage are intended to avoid allogeneic blood transfusions and their associated risks. Although widely investigated, the real effectiveness of these alternative transfusion practices remains controversial. The surgery reports of 600 patients undergoing total joint arthroplasty (312 hip and 288 knee replacements) were retrospectively reviewed to assess transfusion needs and related blood management at our institute. Evaluation parameters included post-operative blood loss, haemoglobin concentration measured at different time points, ASA score, and blood transfusion strategies. Autologous blood donation increased the odds of receiving a red blood cell transfusion. Reinfusion by a cell salvage system of post-operative shed blood was found to limit adverse effects in cases of severe post-operative blood loss. The peri-operative net decrease in haemoglobin concentration was higher in patients who had predeposited autologous blood than in those who had not. The strengths of this study are the high number of cases and the standardised procedures, all operations having been performed by a single orthopaedic surgeon and a single anaesthesiologist. Our data suggest that a pre-operative autologous donation programme may often be useless, if not harmful. Conversely, the use of a cell salvage system may be effective in reducing the impact of blood transfusion on a patient's physiological status. Basal haemoglobin concentration emerged as a useful indicator of transfusion probability in total joint replacement procedures.

Retrospective analysis of the efficacy of perioperative use of the cell salvage and autologous blood recovery system during laparoscopic myomectomy.

PubMed

Kumakiri, Jun; Kikuchi, Iwaho; Kitade, Mari; Matsuoka, Shozo; Kono, Ayako; Takeda, Satoru

2012-04-01

To evaluate the benefit of the intraoperative use of a cell salvage and autologous blood recovery system during laparoscopic myomectomy (LM). We retrospectively reviewed the medical records of 538 patients who underwent LM between January 2008 and December 2009 at our hospital. Patients undergoing LM were divided into two groups depending on whether the cell salvage and autologous blood recovery system was used; the use of the system was at the discretion of the surgeon. The system for intraoperative hemorrhage was employed based on the surgeon's decision. Of the 583 patients, 23 patients (4.3%) underwent LM using the system. No patient required an allogeneic blood transfusion during or after the surgery. The median surgical time (183 vs. 100 m), total blood loss (520 vs. 100 mL), total weight of enucleated myomas (390 vs. 175 g), and postoperative calculated δ-Hemoglobin (δ-Hb) (2 vs. 1.6 g/dL) were significantly increased in the 23 patients in whom the system was used. The median autologous blood volume recovered by intraoperative use of the system and transferred to the 23 patients was 250 mL (range 125-800 mL). For patients in whom the system was not used, the total blood loss significantly correlated to δ-Hb (r = 0.29; P < 0.01). However, there was no such correlation in patients in whom the system was not used (r = 0.04; P = 0.86). The adoption of a cell salvage and autologous blood recovery system during LM was useful for patients with severe hemorrhage.

Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

PubMed Central

Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Martínez Villegas, Octavio; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

2015-01-01

Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy. PMID:25821830

Fabricated autologous epidermal cell sheets for the prevention of esophageal stricture after circumferential ESD in a porcine model.

PubMed

Kanai, Nobuo; Yamato, Masayuki; Ohki, Takeshi; Yamamoto, Masakazu; Okano, Teruo

2012-10-01

Endoscopic submucosal dissection (ESD) is an accepted treatment for early esophageal carcinoma. However, resection of a large mucosal area, as with circumferential ESD, induces severe stricture formation. To evaluate the efficacy of cultured autologous epidermal cell sheets to prevent severe esophageal constriction after circumferential ESD. Animal study. University institute. Eight pigs underwent circumferential esophageal ESD while under general anesthesia. In 4 pigs, fabricated autologous epidermal cell sheets were endoscopically transplanted to the central ESD sites immediately after the ESD. The other 4 pigs underwent circumferential ESD only. Necropsy and histological assessment were performed at 1 and 2 weeks post-ESD. Weight gain, degree of mucosal constriction, and histological assessments. All pigs in the control group showed severe esophageal constriction after 2 weeks. The control and transplanted groups had weight gains of -10.3% and 0.3% (P = .03), respectively, and the mean degrees of constriction were 88% and 56% (P < .01), respectively. Early re-epithelialization and mild fibrosis in the muscularis were observed in the transplanted group. Animal study, small sample size. Fabricated autologous skin epidermal cell sheets would be useful in preventing severe esophageal constriction after circumferential ESD. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

VAGINOPLASTY WITH AUTOLOGOUS BUCCAL MUCOSA FENESTRATED GRAFT IN TWO PATIENTS WITH VAGINAL AGENESIS: A MULTIDISCIPLINARY APPROACH AND LITERATURE REVIEW

PubMed Central

Chan, Jessica L; Levin, Pamela J; Ford, Brian P; Stanton, David C; Pfeifer, Samantha M

2017-01-01

The objective of this case series is to describe the procedure and outcomes of a multidisciplinary approach to vaginoplasty using autologous buccal mucosa fenestrated grafts in two patients with vaginal agenesis. This procedure resulted in anatomic success with a functional neovagina with good vaginal length and caliber and satisfactory sexual function capacity and well healed buccal mucosa. There were no complications and patients were satisfied with surgical results. We conclude that the use of a single fenestrated graft of autologous buccal mucosa is a simple, effective procedure for the treatment of vaginal agenesis that results in an optimally functioning neovagina with respect to vaginal length, caliber, and sexual capacity. PMID:28212868

How we manage autologous stem cell transplantation for patients with multiple myeloma

PubMed Central

Dingli, David

2014-01-01

An estimated 22 350 patients had multiple myeloma diagnosed in 2013, representing 1.3% of all new cancers; 10 710 deaths are projected, representing 1.8% of cancer deaths. Approximately 0.7% of US men and women will have a myeloma diagnosis in their lifetime, and with advances in therapy, 77 600 US patients are living with myeloma. The 5-year survival rate was 25.6% in 1989 and was 44.9% in 2005. The median age at diagnosis is 69 years, with 62.4% of patients aged 65 or older at diagnosis. Median age at death is 75 years. The rate of new myeloma cases has been rising 0.7% per year during the past decade. The most common indication for autologous stem cell transplantation in the United States is multiple myeloma, and this article is designed to provide the specifics of organizing a transplant program for multiple myeloma. We review the data justifying use of stem cell transplantation as initial management in myeloma patients. We provide selection criteria that minimize the risks of transplantation. Specific guidelines on mobilization and supportive care through the transplant course, as done at Mayo Clinic, are given. A review of the data on tandem vs sequential autologous transplants is provided. PMID:24973360

Untested, unproven, and unethical: the promotion and provision of autologous stem cell therapies in Australia.

PubMed

McLean, Alison K; Stewart, Cameron; Kerridge, Ian

2015-02-09

An increasing number of private clinics in Australia are marketing and providing autologous stem cell therapies to patients. Although advocates point to the importance of medical innovation and the primacy of patient choice, these arguments are unconvincing. First, it is a stark truth that these clinics are flourishing while the efficacy and safety of autologous stem cell therapies, outside of established indications for hematopioetic stem cell transplantation, are yet to be shown. Second, few of these therapies are offered within clinical trials. Third, patients with chronic and debilitating illnesses, who are often the ones who take up these therapies, incur significant financial burdens in the expectation of benefiting from these treatments. Finally, the provision of these stem cell therapies does not follow the established pathways for legitimate medical advancement. We argue that greater regulatory oversight and professional action are necessary to protect vulnerable patients and that at this time the provision of unproven stem cell therapies outside of clinical trials is unethical.

Durable donor engraftment after radioimmunotherapy using α-emitter astatine-211–labeled anti-CD45 antibody for conditioning in allogeneic hematopoietic cell transplantation

PubMed Central

Chen, Yun; Kornblit, Brian; Hamlin, Donald K.; Sale, George E.; Santos, Erlinda B.; Wilbur, D. Scott; Storer, Barry E.; Storb, Rainer

2012-01-01

To reduce toxicity associated with external γ-beam radiation, we investigated radioimmunotherapy with an anti-CD45 mAb labeled with the α-emitter, astatine-211 (211At), as a conditioning regimen in dog leukocyte antigen-identical hematopoietic cell transplantation (HCT). Dose-finding studies in 6 dogs treated with 100 to 618 μCi/kg 211At-labeled anti-CD45 mAb (0.5 mg/kg) without HCT rescue demonstrated dose-dependent myelosuppression with subsequent autologous recovery, and transient liver toxicity in dogs treated with 211At doses less than or equal to 405 μCi/kg. Higher doses of 211At induced clinical liver failure. Subsequently, 8 dogs were conditioned with 155 to 625 μCi/kg 211At-labeled anti-CD45 mAb (0.5 mg/kg) before HCT with dog leukocyte antigen-identical bone marrow followed by a short course of cyclosporine and mycophenolate mofetil immunosuppression. Neutropenia (1-146 cells/μL), lymphopenia (0-270 cells/μL), and thrombocytopenia (1500-6560 platelets/μL) with prompt recovery was observed. Seven dogs had long-term donor mononuclear cell chimerism (19%-58%), whereas 1 dog treated with the lowest 211At dose (155 μCi/kg) had low donor mononuclear cell chimerism (5%). At the end of follow-up (18-53 weeks), only transient liver toxicity and no renal toxicity had been observed. In conclusion, conditioning with 211At-labeled anti-CD45 mAb is safe and efficacious and provides a platform for future clinical trials of nonmyeloablative transplantation with radioimmunotherapy-based conditioning. PMID:22134165

Nitric oxide production by nurse shark (Ginglymostoma cirratum) and clearnose skate (Raja eglanteria) peripheral blood leucocytes.

PubMed

Walsh, Cathy J; Toranto, Jason D; Gilliland, C Taylor; Noyes, David R; Bodine, Ashby B; Luer, Carl A

2006-01-01

Reactive nitrogen intermediates, such as nitric oxide (NO), are important immunomodulators in vertebrate immune systems, but have yet to be identified as mediators of host defence in any member of class Chondrichthyes, the cartilaginous fishes. In the present study, production of NO by nurse shark (Ginglymostoma cirratum) peripheral blood leucocytes (PBL) stimulated with bacterial cell wall lipopolysaccharide (LPS) was investigated. PBL were cultured for 24 to 96 h following stimulation with LPS at concentrations ranging from 0 to 25 microg ml(-1), in both serum-supplemented and serum-free culture conditions. Production of NO was measured indirectly using the Griess reaction, with maximal NO production occurring after 72 h using 10% FBS and 10 microg LPS ml(-1). Application of these culture conditions to PBL from another cartilaginous fish (clearnose skate, Raja eglanteria) resulted in a similar NO response. Addition of a specific inhibitor of inducible nitric oxide synthase (iNOS), L-N(6)-(1-iminoethyl)lysine (L-NIL), resulted in a significant decrease in the production of NO by PBL from both species.

Men's preferences for women's body odours are not associated with human leucocyte antigen.

PubMed

Probst, Fabian; Fischbacher, Urs; Lobmaier, Janek S; Wirthmüller, Urs; Knoch, Daria

2017-10-11

Body odours reportedly portray information about an individual's genotype at the major histocompatibility complex (MHC, called human leucocyte antigen, HLA, in humans). While there is strong experimental support for MHC-associated mating behaviour in animals, the situation in humans is more complex. A lot of effort has been spent on testing HLA-associated odour preferences of women. To date, only very few studies have looked at HLA-linked olfactory preferences in men and these studies have revealed inconsistent results. Here, we investigate men's HLA-associated preferences for women's body odours. Importantly, and in contrast to previous studies, these odours were gathered at peak fertility (i.e. just before ovulation) when any HLA-associated odour preferences should be strongest. We scrutinized whether men's preference for women's body odours is influenced by (i) the number of shared HLA alleles between men and women, (ii) HLA heterozygosity, and (iii) the frequency of rare HLA alleles. We found that men could readily differentiate between odours they found attractive and odours they found less attractive, but that these preferences were not associated with HLA. Specifically, men did not prefer odours from women who are HLA dissimilar, HLA heterozygous, or who have rare HLA alleles. Together, these findings suggest that HLA has no effect on men's odour preferences. © 2017 The Author(s).

Food Labels

MedlinePlus

... Staying Safe Videos for Educators Search English Español Food Labels KidsHealth / For Teens / Food Labels What's in ... to have at least 95% organic ingredients. Making Food Labels Work for You The first step in ...

Label Review Training: Module 1: Label Basics, Page 25

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review: clarity, accuracy, consistency with EPA policy, and enforceability.

Label Review Training: Module 1: Label Basics, Page 29

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This page is a quiz on Module 1.

Foreskin-isolated keratinocytes provide successful extemporaneous autologous paediatric skin grafts.

PubMed

Mcheik, Jiad N; Barrault, Christine; Pedretti, Nathalie; Garnier, Julien; Juchaux, Franck; Levard, Guillaume; Morel, Franck; Lecron, Jean-Claude; Bernard, François-Xavier

2016-03-01

Severe burns in children are conventionally treated with split-thickness skin autografts or epidermal sheets. However, neither early complete healing nor quality of epithelialization is satisfactory. An alternative approach is to graft isolated keratinocytes. We evaluated paediatric foreskin and auricular skin as donor sources, autologous keratinocyte transplantation, and compared the graft efficiency to the in vitro capacities of isolated keratinocytes to divide and reconstitute epidermal tissue. Keratinocytes were isolated from surgical samples by enzymatic digestion. Living cell recovery, in vitro proliferation and epidermal reconstruction capacities were evaluated. Differentiation status was analysed, using qRT-PCR and immunolabelling. Eleven children were grafted with foreskin-derived (boys) or auricular (girls) keratinocyte suspensions dripped onto deep severe burns. The aesthetic and functional quality of epithelialization was monitored in a standardized way. Foreskin keratinocyte graft in male children provides for the re-epithelialization of partial deep severe burns and accelerates wound healing, thus allowing successful wound closure, and improves the quality of scars. In accordance, in vitro studies have revealed a high yield of living keratinocyte recovery from foreskin and their potential in terms of regeneration and differentiation. We report a successful method for grafting paediatric males presenting large severe burns through direct spreading of autologous foreskin keratinocytes. This alternative method is easy to implement, improves the quality of skin and minimizes associated donor site morbidity. In vitro studies have highlighted the potential of foreskin tissue for graft applications and could help in tissue selection with the prospect of grafting burns for girls. Copyright © 2013 John Wiley & Sons, Ltd.

Autologous bone marrow stem cell transplantation for the treatment of postoperative hand infection with a skin defect in diabetes mellitus: A case report.

PubMed

Liu, Yihong; Liu, Yuchen; Wang, Pujie; Tian, Haoming; Ai, Jianzhong; Liu, Yangbo; Zhou, Yi; Liu, Zhongwen; Guo, Wenjun; Yang, Shenke

2014-06-01

Among stem cells, autologous mesenchymal stem cells (MSCs) are ideal for transplantation by virtue of limited rejection reactions and marked proliferative ability. This study presents a novel method by which MSCs were harvested from the bone marrow of a patient who presented with severe post-traumatic infection and a non-healing skin defect in the hand, secondary to uncontrolled diabetes mellitus (DM). An autologous MSC suspension was injected into the persistent skin defect after stabilizing the blood glucose level and appropriate infection control. During the course of a regular 18-month postoperative follow-up, the patient exhibited immediate recovery with no transplant-associated complications, as well as no evidence of tumorigenicity. Thus, transplantation of autologous MSCs may play a role in the clinical application of stem cells, particularly for treatment of skin defects following surgery in cases of DM and for those caused by various other traumas.

Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

PubMed Central

Boos, Anja M; Weigand, Annika; Deschler, Gloria; Gerber, Thomas; Arkudas, Andreas; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

2014-01-01

New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 μg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in

Trachea stabilisation with autologous costal cartilage in acquired tracheomalacia: report of two cases.

PubMed

Frimpong-Boateng, K; Aniteye, E

2001-06-01

Post-operative tracheomalacia is a life threatening condition whose management is challenging. Surgical procedures which have been suggested in the literature to manage the condition include tracheostomy, staged thyroid reductions and the use of artificial stents either within the lumen of the tracheobronchial tree or as external support. We report the successful management of two patients using autologous costal cartilage to support the tracheal wall.

Transcoronary sinus delivery of autologous bone marrow and angiogenesis in pig models with myocardial injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vicario, J.; Piva, J.; Pierini, A.

2002-06-01

Purpose: The aim of the investigation is to study myocardial injury on pig model with two objectives: (1) feasibility of stimulating angiogenesis with fresh autologous bone marrow; (2) administration of the same fresh autologous bone marrow via coronary sinus with transitory occlusion. Methods: A controlled study was done in animal model with three phases, in a study group of 12 pigs (bone marrow administration) as well as in control group of 4 pigs (saline administration). Phase 1--production of coronary stenosis and myocardial injury; Phase 2--two weeks later, administration of bone marrow through coronary sinus with 10 min occlusion in themore » study group and saline solution in the control group. Phase 3--two weeks later, histological staining with hematoxylin-eosin and inmunohistochemical staining with monoclonal antibody for smooth muscle {alpha}-actin were conducted on both study and control groups. Results: The percentage of angionenesis observed in the study group was 91% and 0% in control group. Counting of positive actin in affected and control areas showed statistically significant differences in relation to both groups: study group (1.37 vs. 0.79) and control group (0.47 vs. 0.51). The percentage of mononuclear immature cells observed in the myocardium in the study group was 25% and in the control group was 0%. There was no increment in the coronary collateral circulation when comparing coronary angiography. Conclusions: Autologous bone marrow in animal model with experimental myocardial injury enhances angiogenesis, as well as vessels with smooth muscles. The transitory occlusion of the coronary sinus might be an effective way to administer cells as those from the bone marrow.« less

Comparison of mechanical compressive properties of commercial and autologous fibrin glues for tissue engineering applications.

PubMed

Cravens, Matthew G; Behn, Anthony W; Dragoo, Jason L

2017-11-01

Fibrin glues are widely used in orthopedic surgery as adhesives and hemostatic agents. We evaluated the compressive properties of selected fibrin glues in order to identify which are appropriate for tissue regeneration applications subject to compression. Uniaxial unconfined compression tests were performed on fibrin gels prepared from commercial and autologous products: (1) Evicel (Ethicon), (2) Tisseel (Baxter), (3) Angel (Arthrex), and (4) ProPlaz (Biorich). Cyclic loads were applied from 0 to 30% strain for 100cycles at 0.5Hz. Following cyclic testing, specimens were subjected to ramp displacement of 1% strain per second to 80% strain. Throughout cyclic loading, Evicel and Tisseel deformed (shortened) less than Angel at all but one time point, and deformed less than ProPlaz at cycles 10 and 20. The dynamic moduli, peak stress, and strain energy were significantly greater in Tisseel than all other groups. Evicel displayed significantly greater dynamic moduli, peak stress, and strain energy than Angel and ProPlaz. Following cyclic testing, Tisseel and Evicel were significantly less deformed than Angel. No specimens exhibited gross failure during ramp loading to 80% strain. Ramp loading trends mirrored those of cyclic loading. The tested commercial glues were significantly more resistant to compression than the autologous products. The compressive properties of Tisseel were approximately twice those of Evicel. All preparations displayed moduli multiple orders of magnitude less than that of native articular cartilage. We conclude that in knee surgeries requiring fibrin glue to undergo compression of daily activity, commercial products are preferable to autologous preparations from platelet-poor plasma, though both will deform significantly. Copyright © 2017 Elsevier Ltd. All rights reserved.

Potent Autologous and Heterologous Neutralizing Antibody Responses Occur in HIV-2 Infection across a Broad Range of Infection Outcomes

PubMed Central

Aasa-Chapman, Marlén; Cotten, Matthew; Hué, Stéphane; Robinson, James; Bibollet-Ruche, Frederic; Sarge-Njie, Ramu; Berry, Neil; Jaye, Assan; Aaby, Peter; Whittle, Hilton; Rowland-Jones, Sarah; Weiss, Robin

2012-01-01

Few studies have explored the role of neutralizing antibody (NAb) responses in controlling HIV-2 viremia and disease progression. Using a TZM-bl neutralization assay, we assessed heterologous and autologous NAb responses from a community cohort of HIV-2-infected individuals with a broad range of disease outcomes in rural Guinea-Bissau. All subjects (n = 40) displayed exceptionally high heterologous NAb titers (50% inhibitory plasma dilution or 50% inhibitory concentration [IC50], 1:7,000 to 1:1,000,000) against 5 novel primary HIV-2 envelopes and HIV-2 7312A, whereas ROD A and 3 primary envelopes were relatively resistant to neutralization. Most individuals also showed high autologous NAb against contemporaneous envelopes (78% of plasma-envelope combinations in 69 envelopes from 21 subjects), with IC50s above 1:10,000. No association between heterologous or autologous NAb titer and greater control of HIV-2 was found. A subset of envelopes was found to be more resistant to neutralization (by plasma and HIV-2 monoclonal antibodies). These envelopes were isolated from individuals with greater intrapatient sequence diversity and were associated with changes in potential N-linked glycosylation sites but not CD4 independence or CXCR4 use. Plasma collected from up to 15 years previously was able to potently neutralize recent autologous envelopes, suggesting a lack of escape from NAb and the persistence of neutralization-sensitive variants over time, despite significant NAb pressure. We conclude that despite the presence of broad and potent NAb responses in HIV-2-infected individuals, these are not the primary forces behind the dichotomous outcomes observed but reveal a limited capacity for adaptive selection and escape from host immunity in HIV-2 infection. PMID:22072758

Pre-operative autologous donation for minimising perioperative allogeneic blood transfusion

PubMed Central

Henry, David A; Carless, Paul A; Moxey, Annette J; O’Connell, Dianne; Ker, Katharine; Fergusson, Dean A

2014-01-01

Background Public concerns regarding the safety of transfused blood have prompted reconsideration of the indications for the transfusion of allogeneic red cells (blood from an unrelated donor), and a range of techniques designed to minimise transfusion requirements. Objectives To examine the evidence for the efficacy of pre-operative autologous blood donation (PAD) in reducing the need for perioperative allogeneic red blood cell (RBC) transfusion. Search methods Articles were identified by searches of the electronic databases; MEDLINE (January 1950 to July 2009), EMBASE (January 1980 to Week 31, 2009), ISI Web of Science (inception to August 2009), The Cochrane Library 2009, Issue 3, and The Cochrane Injuries Group Specialised Register (searched August 7 2009). Reference lists in relevant publications were checked and authors were contacted to identify additional studies. The searches were updated in August 2009. Selection criteria Randomised controlled trials with a concurrent control group in which adult patients, scheduled for non-urgent surgery, were randomised to PAD, or to a control group who did not receive the intervention. Data collection and analysis Data were independently extracted and the risk of bias was assessed. Relative risks (RR) and mean differences (MD) with 95% confidence intervals (CIs) were calculated. Data were pooled using a random-effects model. The principal outcomes were the proportion of patients exposed to allogeneic red blood cells (RBCs) and the amount of blood transfused. Other clinical outcomes are detailed in the review. Main results Fourteen trials were included. Overall PAD reduced the risk of receiving an allogeneic blood transfusion by a relative 68% (RR 0.32; 95% CI 0.22 to 0.47). The absolute reduction in risk of allogeneic transfusion was 44% (risk difference (RD) −0.44; 95% CI −0.68 to −0.21). In contrast, the results show that the risk of receiving any blood transfusion (allogeneic and/or autologous) is increased by

The fate of autologous endometrial mesenchymal stromal cells after application in the healthy equine uterus.

PubMed

Rink, Elisabeth; Beyer, Teresa; French, Hilari; Watson, Elaine; Aurich, Christine; Donadeu, Xavier

2018-05-23

Because of their distinct differentiation, immunomodulatory and migratory capacities, endometrial mesenchymal stromal cells (MSCs) may provide an optimum source of therapeutic cells not only in relation to the uterus but also for regeneration of other tissues. This study reports the fate of endometrial MSCs following intrauterine application in mares. Stromal cell fractions were isolated from endometrial biopsies taken from seven reproductively healthy mares, expanded and fluorescence-labeled in culture. MSCs (15 x 106) or PBS were autologously infused into each uterine horn during early diestrus and subsequently tracked by fluorescence microscopy and flow cytometry of endometrial biopsies and blood samples taken periodically after infusion. The inflammatory response to cell infusion was monitored in endometrial cytology samples. MSCs were detected in endometrial sections at 6, 12 and 24 hours but not later (7 or 14 days) after cell infusion. Cells were in all cases located in the uterine lumen, never within endometrial tissue. No fluorescence signal was detected in blood samples at any time point after infusion. Cytology analyses showed an increase in %PMN between 1 and 3 hours after uterine infusion with either MSCs or PBS, and a further increase by 6 hours only in mares infused with PBS. In summary, endometrial MSCs were detected in the uterine lumen for up to 24 h after infusion but did not migrate into healthy endometrium. Moreover, MSCs effectively attenuated the inflammatory response to uterine infusion. We conclude that endometrial MSCs obtained from routine uterine biopsies could provide a safe and effective cell source for treatment of inflammatory conditions of the uterus and potentially other tissues.

Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis

PubMed Central

Bell, G M; Anderson, A E; Diboll, J; Reece, R; Eltherington, O; Harry, R A; Fouweather, T; MacDonald, C; Chadwick, T; McColl, E; Dunn, J; Dickinson, A M; Hilkens, C M U; Isaacs, John D

2017-01-01

Objectives To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities. Methods An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×106, 3×106 or 10×106 tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood. Results There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×106 tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high. Conclusion IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×106 tolDC but no systemic clinical or immunomodulatory effects were detectable. Trial registration number NCT01352858. PMID:27117700

A label distance maximum-based classifier for multi-label learning.

PubMed

Liu, Xiaoli; Bao, Hang; Zhao, Dazhe; Cao, Peng

2015-01-01

Multi-label classification is useful in many bioinformatics tasks such as gene function prediction and protein site localization. This paper presents an improved neural network algorithm, Max Label Distance Back Propagation Algorithm for Multi-Label Classification. The method was formulated by modifying the total error function of the standard BP by adding a penalty term, which was realized by maximizing the distance between the positive and negative labels. Extensive experiments were conducted to compare this method against state-of-the-art multi-label methods on three popular bioinformatic benchmark datasets. The results illustrated that this proposed method is more effective for bioinformatic multi-label classification compared to commonly used techniques.

Failure of transplantation tolerance induction by autologous regulatory T cells in the pig-to-non-human primate islet xenotransplantation model.

PubMed

Shin, Jun-Seop; Min, Byoung-Hoon; Kim, Jong-Min; Kim, Jung-Sik; Yoon, Il Hee; Kim, Hyun Je; Kim, Yong-Hee; Jang, Jae Yool; Kang, Hee Jung; Lim, Dong-Gyun; Ha, Jongwon; Kim, Sang-Joon; Park, Chung-Gyu

2016-07-01

Islet allotransplantation is a promising way to treat some type 1 diabetic (T1D) patients with frequent hypoglycemic unawareness, and islet xenotransplantation is emerging to overcome the problem of donor organ shortage. Our recent study showing reproducible long-term survival of porcine islets in non-human primates (NHPs) allows us to examine whether autologous regulatory T-cell (Treg) infusion at peri-transplantation period would induce transplantation tolerance in xenotransplantation setting. Two diabetic rhesus monkeys were transplanted with porcine islets from wild-type adult Seoul National University (SNU) miniature pigs with immunosuppression by anti-thymoglobulin (ATG), cobra venom factor, anti-CD154 monoclonal antibody (mAb), and sirolimus. CD4(+) CD25(high) CD127(low) autologous regulatory T cells from the recipients were isolated, ex vivo expanded, and infused at the peri-transplantation period. Blood glucose and porcine C-peptide from the recipients were measured up to 1000 days. Maintenance immunosuppressants including a CD40-CD154 blockade were deliberately discontinued to confirm whether transplantation tolerance was induced by adoptively transferred Tregs. After pig islet transplantation via portal vein, blood glucose levels of diabetic recipients became normalized and maintained over 6 months while in immunosuppressive maintenance with a CD40-CD154 blockade and sirolimus. However, the engrafted pig islets in the long-term period were fully rejected by activated immune cells, particularly T cells, when immunosuppressants were stopped, showing a failure of transplantation tolerance induction by autologous Tregs. Taken together, autologous Tregs infused at the peri-transplantation period failed to induce transplantation tolerance in pig-to-NHP islet xenotransplantation setting. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Blood management and transfusion strategies in 600 patients undergoing total joint arthroplasty: an analysis of pre-operative autologous blood donation

PubMed Central

Perazzo, Paolo; Viganò, Marco; de Girolamo, Laura; Verde, Francesco; Vinci, Anna; Banfi, Giuseppe; Romagnoli, Sergio

2013-01-01

Background Blood loss during total joint arthroplasty strongly influences the time to recover after surgery and the quality of the recovery. Blood conservation strategies such as pre-operative autologous blood donation and post-operative cell salvage are intended to avoid allogeneic blood transfusions and their associated risks. Although widely investigated, the real effectiveness of these alternative transfusion practices remains controversial. Materials and methods The surgery reports of 600 patients undergoing total joint arthroplasty (312 hip and 288 knee replacements) were retrospectively reviewed to assess transfusion needs and related blood management at our institute. Evaluation parameters included post-operative blood loss, haemoglobin concentration measured at different time points, ASA score, and blood transfusion strategies. Results Autologous blood donation increased the odds of receiving a red blood cell transfusion. Reinfusion by a cell salvage system of post-operative shed blood was found to limit adverse effects in cases of severe post-operative blood loss. The peri-operative net decrease in haemoglobin concentration was higher in patients who had predeposited autologous blood than in those who had not. Discussion The strengths of this study are the high number of cases and the standardised procedures, all operations having been performed by a single orthopaedic surgeon and a single anaesthesiologist. Our data suggest that a pre-operative autologous donation programme may often be useless, if not harmful. Conversely, the use of a cell salvage system may be effective in reducing the impact of blood transfusion on a patient’s physiological status. Basal haemoglobin concentration emerged as a useful indicator of transfusion probability in total joint replacement procedures. PMID:23736922

Thumb carpometacarpal joint resurfacing with autologous ear cartilage.

PubMed

Nickell, William B

2014-05-01

A study was designed to ascertain the long-term effectiveness of using autologous full-thickness ear cartilage to resurface the arthritic face of the trapezium, leaving the body of the trapezium intact. The value of injection of the involved carpometacarpal (CMC) joint with local anesthetic in predicting improvement from the surgery was also studied. An operation was used to enter the CMC joint of the thumb between the thenar muscles and the abductor tendon. The articular surface of the trapezium was resected and resurfaced with full-thickness ear cartilage from the patient's ear. Patients were selected based on constant, unremitting pain. All patients also had x-ray evidence of severe arthritis at the CMC joint of the thumb. Both thumbs were evaluated for pain, range of motion, key and palmar pinch, and grip strength before the surgery and followed up for a minimum of 30 months to be included in the study. Fifty-nine patients had ear cartilage arthroplasty from 1997 to 2007 by the same surgeon with a total of 67 operations (8 patients, all women, had both thumbs operated). Forty-nine of these patients, 4 men and 45 women (53 hands), were available for follow-up and constitute the study group. Eight procedures were done on the left hand, and 45, on the right. There were no ear complications and no cartilage extrusions. All patients had improved range of motion and greatly decreased pain. Strength was equaled or exceeded the unoperated thumb. Preoperative joint injection was a good predictor of postoperative pain relief. All patients were pleased with the result and said that they would have the surgery again. Thumb CMC joint arthroplasty with autologous ear cartilage and preservation of the body of the trapezium is an effective alternative to existing procedures.There is no morbidity to the ear, and predictable long-term improvement in thumb pain and strength can be obtained. Injection of the CMC joint before surgery with local anesthetic is a reliable predictor of

Less label, more free: approaches in label-free quantitative mass spectrometry.

PubMed

Neilson, Karlie A; Ali, Naveid A; Muralidharan, Sridevi; Mirzaei, Mehdi; Mariani, Michael; Assadourian, Gariné; Lee, Albert; van Sluyter, Steven C; Haynes, Paul A

2011-02-01

In this review we examine techniques, software, and statistical analyses used in label-free quantitative proteomics studies for area under the curve and spectral counting approaches. Recent advances in the field are discussed in an order that reflects a logical workflow design. Examples of studies that follow this design are presented to highlight the requirement for statistical assessment and further experiments to validate results from label-free quantitation. Limitations of label-free approaches are considered, label-free approaches are compared with labelling techniques, and forward-looking applications for label-free quantitative data are presented. We conclude that label-free quantitative proteomics is a reliable, versatile, and cost-effective alternative to labelled quantitation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Controversies in autologous and allogeneic hematopoietic cell transplantation in peripheral T/NK-cell lymphomas.

PubMed

Shustov, Andrei

2013-03-01

Peripheral T-cell and NK-cell lymphomas (PT/NKCL) are a heterogeneous group of lymphoid neoplasms with poor outcomes. There is no consensus on the best front line therapy or management of relapsed/refractory disease. The use of autologous and allogeneic hematopoietic cell transplantation (HCT) has been studied in both settings to improve outcomes. Multiple retrospective and several prospective trials were reported. While at first sight the outcomes in the relapsed/refractory setting appear similar in B-cell and T-cell lymphomas when treated with high dose therapy (HDT) and autologous HCT, it is becoming obvious that only specific subtypes of PTCL benefit from this approach (i.e. anaplastic large cell lymphoma [ALCL] and angioimmunoblastic lymphoma [AITL] in second CR). In less favorable histologies, HDT seems to provide limited benefit, with the majority of patients experiencing post-transplant relapse. The use of autologous HCT to consolidate first remission has been evaluated in several prospective trials. Again, the best results were observed in ALCL, but the superiority of this approach over chemotherapy alone needs confirmation in randomized trials. In less favorable histologies, high-dose consolidation resulted in low survival rates comparable to those obtained with chemotherapy alone, and without randomized trials it is hard to recommend this strategy to all patients with newly diagnosed PT/NKCL. Allogeneic HCT might provide potent and potentially curative graft-vs-lymphoma effect and overcome chemotherapy resistance. Only a few studies have been reported to date on allogeneic HCT in PT/NKCL. Based on available data, eligible patients benefit significantly from this approach, with 50% or more patients achieving long-term disease control or cure, although at the expense of significant treatment related mortality (TRM). Reduced-intensity conditioning regimens appear to have lower TRM and might extend this approach to older patients. With the recent approval of

Open wedge high tibial osteotomies: Calcium-phosphate ceramic spacer versus autologous bonegraft.

PubMed

Gouin, F; Yaouanc, F; Waast, D; Melchior, B; Delecrin, J; Passuti, N

2010-10-01

Valgus tibial osteotomy (VTO) is a well-known procedure for the treatment of medial compartment femoro-tibial osteoarthritis. Good and very good results have been reported with calcium phosphate wedges, which avoid the inconveniences of autologous grafts use. The hypothesis of this study is that with equivalent results in the treatment of osteoarthritis of the knee, the use of calcium phosphate wedges (BMCaPh) to fill the bone defect created by osteotomy would result in fewer specific complications and less pain associated with autologous grafts (AUTO) harvesting. This prospective, controlled, randomised study included one arm that received a macroporous, biphasic calcium phosphate wedge (BMCaPh group) and one arm that received an autologous tricortical graft (AUTO group) for filling. The same plate with locked screws was used for fixation in all cases. All patients underwent at least two years of clinical and radiographic post-operative follow-up. Forty patients were included. Loss of correction occurred in six of the twenty-two patients in the BMCaPh group (27%), resulting in three early surgical revisions, compared to one loss of correction in the AUTO group. Lateral cortical hinge tears were a risk factor for loss of correction for the entire cohort and in the BMCaPh group. (relative risk 13.3 [1.9-92]. Moreover, union took significantly longer and pain lasted significantly longer in the BMCaPh group, although results were comparable at 6 months. A significant number of undesirable events (loss of correction) occurred in this study, limiting the number of included patients. Nevertheless, the results show that although there was no difference in the two groups for overall complications, number of revisions all causes combined, or clinical results, filling with BMCaPh was less tolerated and increased the risk of loss of correction when local mechanical conditions of the knee were unfavourable (lateral cortical hinge tears). Moreover, although it is not possible

Chronic Traumatic Giant Macular Hole Repair with Autologous Platelets.

PubMed

Coca, Mircea; Makkouk, Fuad; Picciani, Renata; Godley, Bernard; Elkeeb, Ahmed

2017-01-05

We report on the closure of a chronic posttraumatic giant macular hole. The patient presented with decreased vision in the left eye following blunt trauma 20 years prior. His dilated fundus examination revealed a 3000 um base-diameter full thickness macular hole. Surgical repair was performed with pars plana vitrectomy (PPV), internal limiting membrane peeling and autologous platelet concentrate (APC) injected over the macular hole. At one month follow-up, the macular hole had closed on exam and optical coherence tomography (OCT), and the patient reported subjective visual improvement. To our knowledge, this report presents the first case of a chronic giant macular hole successfully closed after undergoing surgery with adjuvant platelets therapy.

Achieving ideal donor site aesthetics with autologous breast reconstruction

PubMed Central

2015-01-01

The appearance of the donor site following breast reconstruction with abdominal flaps has become an important topic for study. Given the variety of flaps that are derived from the abdomen, decisions are often based on how much muscle and fascia will be harvested. Comparisons between muscle sparing and non-muscle sparing techniques have been performed with outcomes related to function and contour. Closure techniques will vary and include primary fascial closure, mesh reinforcement and additional fascial plication all of which can produce natural and sometimes improved abdominal contours. Proper patient selection however is important. This manuscript will describe various techniques in order to achieve ideal abdominal contour following autologous reconstruction. PMID:26005646

Chronic Traumatic Giant Macular Hole Repair with Autologous Platelets

PubMed Central

Makkouk, Fuad; Picciani, Renata; Godley, Bernard; Elkeeb, Ahmed

2017-01-01

We report on the closure of a chronic posttraumatic giant macular hole. The patient presented with decreased vision in the left eye following blunt trauma 20 years prior. His dilated fundus examination revealed a 3000 um base-diameter full thickness macular hole. Surgical repair was performed with pars plana vitrectomy (PPV), internal limiting membrane peeling and autologous platelet concentrate (APC) injected over the macular hole. At one month follow-up, the macular hole had closed on exam and optical coherence tomography (OCT), and the patient reported subjective visual improvement. To our knowledge, this report presents the first case of a chronic giant macular hole successfully closed after undergoing surgery with adjuvant platelets therapy. PMID:28168133

Autologous cell therapies: challenges in US FDA regulation.

PubMed

McAllister, Todd N; Audley, David; L'Heureux, Nicolas

2012-11-01

Cell-based therapies (CBTs) have been hailed for the last two decades as the next pillar of healthcare, yet the clinical and commercial potential of regenerative medicine has yet to live up to the hype. While recent analysis has suggested that regenerative medicine is maturing into a multibillion dollar industry, examples of clinical and commercial success are still relatively rare. With 30 years of laboratory and clinical efforts fueled by countless billions in public and private funding, one must contemplate why CBTs have not made a greater impact. The current regulatory environment, with its zero-risk stance, stymies clinical innovation while fueling a potentially risky medical tourism industry. Here, we highlight the challenges the US FDA faces and present talking points for an improved regulatory framework for autologous CBTs.

Adoptive cell transfer using autologous tumor infiltrating lymphocytes in gynecologic malignancies.

PubMed

Mayor, Paul; Starbuck, Kristen; Zsiros, Emese

2018-05-23

During the last decade, the field of cancer immunotherapy has been entirely transformed by the development of new and more effective treatment modalities with impressive response rates and the prospect of long survival. One of the major breakthroughs is adoptive cell transfer (ACT) based on autologous T cells derived from tumor-infiltrating lymphocytes (TILs). TIL-based ACT is a highly personalized cancer treatment. T cells are harvested from autologous fresh tumor tissues, and after ex vivo activation and extensive expansion, are reinfused to patients. TIL-based therapies have only been offered in small phase I/II studies in a few centers given the highly specialized care required, the complexity of TIL production and the very intensive nature of the three-step treatment protocol. The treatment includes high-dose lymphodepleting chemotherapy, the infusion of the expanded and activated T cells and interleukin-2 (IL-2) injections to increase survival of the T cells. Despite the limited data on ACT, the small published studies consistently confirm an impressive clinical response rate of up to 50% in metastatic melanoma patients, including a significant proportion of patients with durable complete response. These remarkable results justify the need for larger clinical trials in other solid tumors, including gynecologic malignancies. In this review we provide an overview of the current clinical results, future applications of TIL-based ACT in gynecologic malignancies, and on risks and challenges associated with modern T cell therapy. Copyright © 2018. Published by Elsevier Inc.

Soft Tissue Repair with Easy-Accessible Autologous Newborn Placenta or Umbilical Cord Blood in Severe Malformations: A Primary Evaluation

PubMed Central

2017-01-01

Disrupted organogenesis leads to permanent malformations that may require surgical correction. Autologous tissue grafts may be needed in severe lack of orthotopic tissue but include donor site morbidity. The placenta is commonly discarded after birth and has a therapeutic potential. The aim of this study was to determine if the amnion from placenta or plasma rich of growth factors (PRGF) with mononuclear cells (MNC) from umbilical cord blood (UCB), collected noninvasively, could be used as bio-constructs for autologous transplantation as an easy-accessible no cell culture-required method. Human amnion and PRGF gel were isolated and kept in culture for up to 21 days with or without small intestine submucosa (SIS). The cells in the constructs showed a robust phenotype without induced increased proliferation (Ki67) or apoptosis (caspase 3), but the constructs showed decreased integrity of the amnion-epithelial layer at the end of culture. Amnion-residing cells in the SIS constructs expressed CD73 or pan-cytokeratin, and cells in the PRGF-SIS constructs expressed CD45 and CD34. This study shows that amnion and UCB are potential sources for production of autologous grafts in the correction of congenital soft tissue defects. The constructs can be made promptly after birth with minimal handling or cell expansion needed. PMID:29403534

PRGF exerts more potent proliferative and anti-inflammatory effects than autologous serum on a cell culture inflammatory model.

PubMed

Anitua, E; Muruzabal, F; de la Fuente, M; Riestra, A; Merayo-Lloves, J; Orive, G

2016-10-01

Ocular graft versus host disease (oGVHD) is part of a systemic inflammatory disease that usually affects ocular surface tissues manifesting as a dry eye syndrome. Current treatments provide unsatisfactory results. Blood-derived products, like plasma rich in growth factors (PRGF) emerge as a potential therapy for this disease. The purpose of this study was to evaluate the tissue regeneration and anti-inflammatory capability of PRGF, an autologous platelet enriched plasma eye-drop, compared to autologous serum (AS) obtained from oGVHD patients on ocular surface cells cultured in a pro-inflammatory environment. PRGF and AS were obtained from four GVHD patients. Cell proliferation and inflammation markers, intercellular adhesion molecule-1 (ICAM-1) and cyclooxygenase-2 (COX-2), were measured in corneal and conjunctival fibroblastic cells cultured under pro-inflammatory conditions and after treatment with PRGF or AS eye drops. Moreover, cell proliferation increased after treatment with PRGF and AS, though this enhancement in the case of keratocytes was significantly higher with PRGF. PRGF eye drops showed a significant reduction of both inflammatory markers with respect to the initial inflammatory situation and to the AS treatment. Our results concluded that PRGF exerts more potent regenerative and anti-inflammatory effects than autologous serum on ocular surface fibroblasts treated with pro-inflammatory IL-1β and TNFα. Copyright © 2016 Elsevier Ltd. All rights reserved.

Systematic Comparison of Label-Free, Metabolic Labeling, and Isobaric Chemical Labeling for Quantitative Proteomics on LTQ Orbitrap Velos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhou; Adams, Rachel M; Chourey, Karuna

2012-01-01

A variety of quantitative proteomics methods have been developed, including label-free, metabolic labeling, and isobaric chemical labeling using iTRAQ or TMT. Here, these methods were compared in terms of the depth of proteome coverage, quantification accuracy, precision, and reproducibility using a high-performance hybrid mass spectrometer, LTQ Orbitrap Velos. Our results show that (1) the spectral counting method provides the deepest proteome coverage for identification, but its quantification performance is worse than labeling-based approaches, especially the quantification reproducibility; (2) metabolic labeling and isobaric chemical labeling are capable of accurate, precise, and reproducible quantification and provide deep proteome coverage for quantification. Isobaricmore » chemical labeling surpasses metabolic labeling in terms of quantification precision and reproducibility; (3) iTRAQ and TMT perform similarly in all aspects compared in the current study using a CID-HCD dual scan configuration. Based on the unique advantages of each method, we provide guidance for selection of the appropriate method for a quantitative proteomics study.« less

Rational Autologous Cell Sources For Therapy of Heart Failure - Vehicles and Targets For Gene and RNA Therapies.

PubMed

Lampinen, Milla; Vento, Antti; Laurikka, Jari; Nystedt, Johanna; Mervaala, Eero; Harjula, Ari; Kankuri, Esko

2016-01-01

This review focuses on the possibilities for intraoperative processing and isolation of autologous cells, particularly atrial appendage-derived cells (AADCs) and cellular micrografts, and their straightforward use in cell transplantation for heart failure therapy. We review the potential of autologous tissues to serve as sources for cell therapy and consider especially those tissues that are used in surgery but from which the excess is currently discarded as surgical waste. We compare the inculture expanded cells to the freshly isolated ones in terms of evidence-based cost-efficacy and their usability as gene- and RNA therapy vehicles. We also review how financial and authority-based decisions and restrictions sculpt the landscape for patients to participate in academic-based trials. Finally, we provide an insight example into AADCs isolation and processing for epicardial therapy during coronary artery bypass surgery.

Enhancement of the repair of dog alveolar cleft by an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture.

PubMed

Yuanzheng, Chen; Yan, Gao; Ting, Li; Yanjie, Fu; Peng, Wu; Nan, Bai

2015-05-01

Autologous bone graft has been regarded as the criterion standard for the repair of alveolar cleft. However, the most prominent issue in alveolar cleft treatment is the high absorption rate of the bone graft. The authors' objective was to investigate the effects of an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture on the repair of dog alveolar cleft. Twenty beagle dogs with unilateral alveolar clefts created by surgery were divided randomly into four groups: group A underwent repair with an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture; group B underwent repair with autologous iliac bone and bone marrow-derived mesenchymal stem cells; group C underwent repair with autologous iliac bone and platelet-rich fibrin; and group D underwent repair with autologous iliac bone as the control. One day and 6 months after transplantation, the transplant volumes and bone mineral density were assessed by quantitative computed tomography. All of the transplants were harvested for hematoxylin and eosin staining 6 months later. Bone marrow-derived mesenchymal stem cells and platelet-rich fibrin transplants formed the greatest amounts of new bone among the four groups. The new bone formed an extensive union with the underlying maxilla in groups A, B, and C. Transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture retained the majority of their initial volume, whereas the transplants in the control group showed the highest absorption rate. Bone mineral density of transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture 6 months later was significantly higher than in the control group (p < 0.05), and was the highest in bone marrow-derived mesenchymal stem cells and platelet-rich fibrin mixed transplants. Hematoxylin and eosin staining showed that the structure of new bones formed the best

An Autologous Muscle Tissue Expansion Approach for the Treatment of Volumetric Muscle Loss

DTIC Science & Technology

2015-07-01

potential therapy for some VML indications, autologous minced muscle grafts (1mm3 pieces of muscle ) are effective in promoting remarkable de novo fiber ...may be misaligned.9–12 More recently, minced muscle grafts were effective in promoting de novomus- cle fiber regeneration and functional recovery in...to enable torque stabilization. The contribution of the tenotomized EDL muscle was negligible in this testing system.13 Peak TA muscle isometric torque

101 Labeled Brain Images and a Consistent Human Cortical Labeling Protocol

PubMed Central

Klein, Arno; Tourville, Jason

2012-01-01

We introduce the Mindboggle-101 dataset, the largest and most complete set of free, publicly accessible, manually labeled human brain images. To manually label the macroscopic anatomy in magnetic resonance images of 101 healthy participants, we created a new cortical labeling protocol that relies on robust anatomical landmarks and minimal manual edits after initialization with automated labels. The “Desikan–Killiany–Tourville” (DKT) protocol is intended to improve the ease, consistency, and accuracy of labeling human cortical areas. Given how difficult it is to label brains, the Mindboggle-101 dataset is intended to serve as brain atlases for use in labeling other brains, as a normative dataset to establish morphometric variation in a healthy population for comparison against clinical populations, and contribute to the development, training, testing, and evaluation of automated registration and labeling algorithms. To this end, we also introduce benchmarks for the evaluation of such algorithms by comparing our manual labels with labels automatically generated by probabilistic and multi-atlas registration-based approaches. All data and related software and updated information are available on the http://mindboggle.info/data website. PMID:23227001

Use of biosimilar filgrastim compared with lenograstim in autologous haematopoietic stem-cell transplant and in sibling allogeneic transplant

PubMed Central

Uddin, Shab; Russell, Pippa; Farrell, Maresa; Davy, Barbara; Taylor, Joe

2015-01-01

Objectives: Biosimilar filgrastim was compared with lenograstim for autologous haematopoietic stem-cell transplant (HSCT) in patients with haematological malignancies. Data from a separate group of sibling donors who underwent allogeneic HSCT are also reported. Methods: Patients with lymphoma or multiple myeloma (MM) who underwent autologous HSCT with biosimilar filgrastim were compared with a historical control group of patients who received lenograstim. Peripheral blood (PB) cells counts were monitored after 7–8 consecutive days of granulocyte-colony stimulating factor (G-CSF) injection and apheresis was performed on day 8 if PB CD34+ cell count was ⩾10 cells/µl. The target PB CD34+ cell doses were ⩾2.0 × 106/kg (lymphoma), ⩾4.0 × 106/kg (MM ⩾60 years old) or ⩾8.0 × 106/kg (MM <60 years old). Results: A total of 259 patients were included in the autologous HSCT comparison (biosimilar filgrastim, n = 104; lenograstim, n = 155). In patients with lymphoma and older MM patients (⩾60 years old), no significant differences were observed between groups with regard to stem-cell mobilization parameters. However, in MM patients <60 years old, all parameters were significantly superior in the biosimilar filgrastim group, including the need for 1 rather than 2 apheresis procedures. No significant differences were observed between groups in median number of days to absolute neutrophil count (ANC) or platelet recovery. In the allogeneic setting, 47 sibling donors received biosimilar filgrastim. Mean CD34+ count at the first apheresis was 6.1 × 106/kg. A total of 13 donors needed a second apheresis and 4 required a third. Among recipients, median days to ANC recovery was 16 (10–28) and to platelet recovery was 13 (9–54). Conclusions: Biosimilar filgrastim is as effective as lenograstim for autologous HSCT in patients with lymphoma or MM patients ⩾60 years old. However, mobilization with biosimilar filgrastim appeared to be

Scaffold-Based Delivery of Autologous Mesenchymal Stem Cells for Mandibular Distraction Osteogenesis: Preliminary Studies in a Porcine Model

PubMed Central

Sun, Zongyang; Tee, Boon Ching; Kennedy, Kelly S.; Kennedy, Patrick M.; Kim, Do-Gyoon; Mallery, Susan R.; Fields, Henry W.

2013-01-01

Purpose Bone regeneration through distraction osteogenesis (DO) is promising but remarkably slow. To accelerate it, autologous mesenchymal stem cells have been directly injected to the distraction site in a few recent studies. Compared to direct injection, a scaffold-based method can provide earlier cell delivery with potentially better controlled cell distribution and retention. This pilot project investigated a scaffold-based cell-delivery approach in a porcine mandibular DO model. Materials and Methods Eleven adolescent domestic pigs were used for two major sets of studies. The in-vitro set established methodologies to: aspirate bone marrow from the tibia; isolate, characterize and expand bone marrow-derived mesenchymal stem cells (BM-MSCs); enhance BM-MSC osteogenic differentiation using FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in-vivo set transplanted autologous stem cells into the mandibular distraction sites using Gelfoam scaffolds; completed a standard DO-course and assessed bone regeneration by macroscopic, radiographic and histological methods. Repeated-measure ANOVAs and t-tests were used for statistical analyses. Results From aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained viability and proliferative ability. After integration with Gelfoam scaffolds, 2.4–5.8×107 autologous BM-MSCs (undifferentiated or differentiated) were transplanted to each experimental DO site. Among 8 evaluable DO sites included in the final analyses, the experimental DO sites demonstrated less interfragmentary mobility, more advanced gap obliteration, higher mineral content and faster mineral apposition than the control sites, and all transplanted scaffolds were completely

In Silico Labeling: Predicting Fluorescent Labels in Unlabeled Images.

PubMed

Christiansen, Eric M; Yang, Samuel J; Ando, D Michael; Javaherian, Ashkan; Skibinski, Gaia; Lipnick, Scott; Mount, Elliot; O'Neil, Alison; Shah, Kevan; Lee, Alicia K; Goyal, Piyush; Fedus, William; Poplin, Ryan; Esteva, Andre; Berndl, Marc; Rubin, Lee L; Nelson, Philip; Finkbeiner, Steven

2018-04-19

Microscopy is a central method in life sciences. Many popular methods, such as antibody labeling, are used to add physical fluorescent labels to specific cellular constituents. However, these approaches have significant drawbacks, including inconsistency; limitations in the number of simultaneous labels because of spectral overlap; and necessary perturbations of the experiment, such as fixing the cells, to generate the measurement. Here, we show that a computational machine-learning approach, which we call "in silico labeling" (ISL), reliably predicts some fluorescent labels from transmitted-light images of unlabeled fixed or live biological samples. ISL predicts a range of labels, such as those for nuclei, cell type (e.g., neural), and cell state (e.g., cell death). Because prediction happens in silico, the method is consistent, is not limited by spectral overlap, and does not disturb the experiment. ISL generates biological measurements that would otherwise be problematic or impossible to acquire. Copyright © 2018 Elsevier Inc. All rights reserved.

Autologous aldrithiol-2-inactivated HIV-1 combined with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose as a vaccine platform for therapeutic dendritic cell immunotherapy.

PubMed

Miller, Elizabeth; Spadaccia, Meredith; Sabado, Rachel; Chertova, Elena; Bess, Julian; Trubey, Charles Mac; Holman, Rose Marie; Salazar, Andres; Lifson, Jeffrey; Bhardwaj, Nina

2015-01-03

Therapeutic interventions for HIV-1 that successfully augment adaptive immunity to promote killing of infected cells may be a requisite component of strategies to reduce latent cellular reservoirs. Adoptive immunotherapies utilizing autologous monocyte-derived dendritic cells (DCs) that have been activated and antigen loaded ex vivo may serve to circumvent defects in DC function that are present during HIV infection in order to enhance adaptive immune responses. Here we detail the clinical preparation of DCs loaded with autologous aldrithiol-2 (AT-2)-inactivated HIV that have been potently activated with the viral mimic, Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (Poly-ICLC). HIV is first propagated from CD4+ T cells from HIV-infected donors and then rendered non-replicative by chemical inactivation with aldrithiol-2 (AT-2), purified, and quantified. Viral inactivation is confirmed through measurement of Tat-regulated β-galactosidase reporter gene expression following infection of TZM-bl cells. In-process testing for sterility, mycoplasma, LPS, adventitious agents, and removal of AT-2 is performed on viral preparations. Autologous DCs are generated and pulsed with autologous AT-2-inactivated virus and simultaneously stimulated with Poly-ICLC to constitute the final DC vaccine product. Phenotypic identity, maturation, and induction of HIV-specific adaptive immune responses are confirmed via flow cytometric analysis of DCs and cocultured autologous CD4+ and CD8+ T cells. Lot release criteria for the DC vaccine have been defined in accordance with Good Manufacturing Practice (GMP) guidelines. The demonstrated feasibility of this approach has resulted in approval by the FDA for investigational use in antiretroviral (ART) suppressed individuals. We discuss how this optimized DC formulation may enhance the quality of anti-HIV adaptive responses beyond what has been previously observed during DC immunotherapy trials for HIV infection. Copyright

Autologous platelet-rich plasma: a potential therapeutic tool for promoting hair growth.

PubMed

Li, Zheng Jun; Choi, Hye-In; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Im, Myung; Seo, Young-Joon; Lee, Young-Ho; Lee, Jeung-Hoon; Lee, Young

2012-07-01

Recently, autologous platelet-rich plasma (PRP) has attracted attention in various medical fields, including plastic and orthopedic surgery and dermatology, for its ability to promote wound healing. PRP has been tested during facelift and hair transplantation to reduce swelling and pain and to increase hair density. To investigate the effects of PRP on hair growth using in vivo and in vitro models. PRP was prepared using the double-spin method and applied to dermal papilla (DP) cells. The proliferative effect of activated PRP on DP cells was measured. To understand the mechanisms of activated PRP on hair growth, we evaluated signaling pathways. In an in vivo study, mice received subcutaneous injections of activated PRP, and their results were compared with control mice. Activated PRP increased the proliferation of DP cells and stimulated extracellular signal-regulated kinase (ERK) and Akt signaling. Fibroblast growth factor 7 (FGF-7) and beta-catenin, which are potent stimuli for hair growth, were upregulated in DP cells. The injection of mice with activated PRP induced faster telogen-to-anagen transition than was seen on control mice. Although few studies tested the effects of activated PRP on hair growth, this research provides support for possible clinical application of autologous PRP and its secretory factors for promotion of hair growth. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Autologous hematopoietic stem cell transplantation in peripheral T-cell lymphoma using a uniform high-dose regimen.

PubMed

Smith, S D; Bolwell, B J; Rybicki, L A; Brown, S; Dean, R; Kalaycio, M; Sobecks, R; Andresen, S; Hsi, E D; Pohlman, B; Sweetenham, J W

2007-08-01

The role of high-dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell non-Hodgkin's lymphoma (NHL) have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Some retrospective studies have found comparable survival rates for patients with T- and B-cell NHL. In this study, we report our single-center experience of ASCT over one decade using a uniform chemotherapy-only high-dose regimen. Thirty-two patients with PTCL-unspecified (PTCL-u; 11 patients) and anaplastic large-cell lymphoma (21 patients) underwent autologous stem cell transplant, mostly for relapsed or refractory disease. The preparative regimen consisted of busulfan, etoposide and cyclophosphamide. Kaplan-Meier 5-year overall survival (OS) and relapse-free survival (RFS) are 34 and 18%, respectively. These results suggest a poor outcome for patients with PTCL after ASCT, and new therapies for T-cell lymphoma are needed.

Do nutrition labels influence healthier food choices? Analysis of label viewing behaviour and subsequent food purchases in a labelling intervention trial.

PubMed

Ni Mhurchu, Cliona; Eyles, Helen; Jiang, Yannan; Blakely, Tony

2018-02-01

There are few objective data on how nutrition labels are used in real-world shopping situations, or how they affect dietary choices and patterns. The Starlight study was a four-week randomised, controlled trial of the effects of three different types of nutrition labels on consumer food purchases: Traffic Light Labels, Health Star Rating labels, or Nutrition Information Panels (control). Smartphone technology allowed participants to scan barcodes of packaged foods and receive randomly allocated labels on their phone screen, and to record their food purchases. The study app therefore provided objectively recorded data on label viewing behaviour and food purchases over a four-week period. A post-hoc analysis of trial data was undertaken to assess frequency of label use, label use by food group, and association between label use and the healthiness of packaged food products purchased. Over the four-week intervention, study participants (n = 1255) viewed nutrition labels for and/or purchased 66,915 barcoded packaged products. Labels were viewed for 23% of all purchased products, with decreasing frequency over time. Shoppers were most likely to view labels for convenience foods, cereals, snack foods, bread and bakery products, and oils. They were least likely to view labels for sugar and honey products, eggs, fish, fruit and vegetables, and meat. Products for which participants viewed the label and subsequently purchased the product during the same shopping episode were significantly healthier than products where labels were viewed but the product was not subsequently purchased: mean difference in nutrient profile score -0.90 (95% CI -1.54 to -0.26). In a secondary analysis of a nutrition labelling intervention trial, there was a significant association between label use and the healthiness of products purchased. Nutrition label use may therefore lead to healthier food purchases. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

TOOTH (The Open study Of dental pulp stem cell Therapy in Humans): Study protocol for evaluating safety and feasibility of autologous human adult dental pulp stem cell therapy in patients with chronic disability after stroke.

PubMed

Nagpal, Anjali; Kremer, Karlea L; Hamilton-Bruce, Monica A; Kaidonis, Xenia; Milton, Austin G; Levi, Christopher; Shi, Songtao; Carey, Leeanne; Hillier, Susan; Rose, Miranda; Zacest, Andrew; Takhar, Parabjit; Koblar, Simon A

2016-07-01

Stroke represents a significant global disease burden. As of 2015, there is no chemical or biological therapy proven to actively enhance neurological recovery during the chronic phase post-stroke. Globally, cell-based therapy in stroke is at the stage of clinical translation and may improve neurological function through various mechanisms such as neural replacement, neuroprotection, angiogenesis, immuno-modulation, and neuroplasticity. Preclinical evidence in a rodent model of middle cerebral artery ischemic stroke as reported in four independent studies indicates improvement in neurobehavioral function with adult human dental pulp stem cell therapy. Human adult dental pulp stem cells present an exciting potential therapeutic option for improving post-stroke disability. TOOTH (The Open study Of dental pulp stem cell Therapy in Humans) will investigate the use of autologous stem cell therapy for stroke survivors with chronic disability, with the following objectives: (a) determine the maximum tolerable dose of autologous dental pulp stem cell therapy; (b) define that dental pulp stem cell therapy at the maximum tolerable dose is safe and feasible in chronic stroke; and (c) estimate the parameters of efficacy required to design a future Phase 2/3 clinical trial. TOOTH is a Phase 1, open-label, single-blinded clinical trial with a pragmatic design that comprises three stages: Stage 1 will involve the selection of 27 participants with middle cerebral artery ischemic stroke and the commencement of autologous dental pulp stem cell isolation, growth, and testing in sequential cohorts (n = 3). Stage 2 will involve the transplantation of dental pulp stem cell in each cohort of participants with an ascending dose and subsequent observation for a 6-month period for any dental pulp stem cell-related adverse events. Stage 3 will investigate the neurosurgical intervention of the maximum tolerable dose of autologous dental pulp stem cell followed by 9 weeks of intensive task

Distribution of leucocyte subsets in the canine respiratory tract.

PubMed

Peeters, D; Day, M J; Farnir, F; Moore, P; Clercx, C

2005-05-01

Histochemistry and immunohistochemistry were used to characterize leucocyte subsets in the respiratory tract of 15 outbred dogs (five aged <6 months and 10 aged >1 year) that had no evidence of respiratory disease. No organized nose- or bronchus-associated lymphoid tissue was observed in any of the sections examined. IgA(+) plasma cells predominated in nasal mucosa and in all parts of the bronchial tree, with fewer IgG(+) and IgM(+) plasma cells. The numbers of IgA(+) and IgM(+) cells were significantly greater in the nasal mucosa than in any other part of the respiratory mucosa. There were significantly fewer IgA(+), IgG(+) and IgM(+) cells in all parts of the respiratory tract in the puppies than in the adults. The number and distribution of mast cells and cells expressing MHC class II, L1 or CD1c were recorded. Mast cells were mainly found in the subepithelial lamina propria of nasal and bronchial mucosa and in the alveolar interstitium, and cells expressing IgE had a similar distribution. Mast cells were also present within muscle layers of the bronchial tree. The numbers of mast cells and MHC class II(+) cells were significantly greater in the nasal mucosa than in any other part of the respiratory mucosa. In the nose, carina and primary and secondary bronchus, there were significantly more mast cells and MHC class II(+) cells in puppies than in adult dogs, whereas the numbers of L1(+) cells and CD1c(+) cells in most sites were significantly greater in older dogs. There were significantly more CD3(+) and CD8(+) cells in the nasal mucosa than in any part of the bronchial mucosa. In most parts of the respiratory mucosa, CD4(+), CD8(+) and TCR alphabeta(+) cells were present in significantly greater numbers in adults than in puppies. All parts of the respiratory tract had similar numbers of mucosal CD4(+) and CD8(+) T lymphocytes. TCR gammadelta(+) cells were absent or sparse in all samples. These data, obtained from dogs without respiratory disease, will enable

Intraarticular injection autologous platelet-rich plasma and bone marrow concentrate in a goat osteoarthritis model.

PubMed

Wang, Zhen; Zhai, Chenjun; Fei, Hao; Hu, Junzheng; Cui, Weiding; Wang, Zhen; Li, Zeng; Fan, Weimin

2018-02-21

To evaluate the effects of intraarticular injections of autologous platelet-rich plasma (PRP) or bone marrow concentrate (BMC) on osteoarthritis (OA), 24 adult goats were equally divided into control (Ctrl), saline (NS), PRP, and BMC groups, and OA was induced by surgery in NS, PRP, and BMC groups. Autologous PRP and BMC were obtained from whole blood and bone marrow aspirates, respectively. The data revealed, platelets were increased in BMC by 1.8-fold, monocytes by 5.6-fold, TGF-β1 by 7.7-fold, and IGF-1 by 3.6-fold (p < 0.05), and platelets were increased in PRP by 2.9-fold, and TGF-β1 by 3.3-fold (p < 0.05). From the sixth week post-operation, saline, PRP, and BMC were administered by intraarticular injection once every 4 weeks, three consecutive times. After the animals were sacrificed, inflammatory cytokines in the synovial fluid was measured, and bone and cartilage degeneration progression was observed by macroscopy, histology, and immunohistochemistry. Compared with the NS group, the level of inflammatory cytokines was reduced in the PRP and BMC groups (p < 0.05). Histologically, delayed cartilage degeneration and higher levels of extracellular matrix (ECM) were observed in both PRP and BMC treated groups (p < 0.05). Furthermore, the BMC group showed greater cartilage protection and less ECM loss than the PRP group (p < 0.05). In summary, this study showed that intraarticular injection of autologous PRP and BMC has therapeutic efficacy in a goat osteoarthritis model, with the greater benefit in terms of cartilage protection being observed in the BMC-treated group than PRP. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Bone formation in sinus augmentation procedures using autologous bone, porcine bone, and a 50 : 50 mixture: a human clinical and histological evaluation at 2 months.

PubMed

Cassetta, Michele; Perrotti, Vittoria; Calasso, Sabrina; Piattelli, Adriano; Sinjari, Bruna; Iezzi, Giovanna

2015-10-01

The aim of this study was to perform a 2 months clinical and histological comparison of autologous bone, porcine bone, and a 50 : 50 mixture in maxillary sinus augmentation procedures. A total of 10 consecutive patients, undergoing two-stage sinus augmentation procedures using 100% autologous bone (Group A), 100% porcine bone (Group B), and a 50 : 50 mixture of autologous and porcine bone (Group C) were included in this study. After a 2-month healing period, at the time of implant insertion, clinical evaluation was performed and bone core biopsies were harvested and processed for histological analysis. The postoperative healing was uneventful regardless of the materials used for the sinus augmentation procedures. The histomorphometrical analysis revealed comparable percentages of newly formed bone, marrow spaces, and residual grafted material in the three groups. The clinical and histological results of this study indicated that porcine bone alone or in combination with autologous bone are biocompatible and osteoconductive materials and can be successfully used in sinus augmentation procedures. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immediate Wheal Reactivity to Autologous Sweat in Atopic Dermatitis Is Associated with Clinical Severity, Serum Total and Specific IgE and Sweat Tryptase Activity.

PubMed

Ilves, Tiina; Virolainen, Anu; Harvima, Ilkka Tapani

2016-01-01

Sweating can worsen atopic dermatitis (AD). The purpose of this work was to study the associations between reactivity to autologous sweat and the clinical severity of AD as well as investigate the possible wheal-inducing factors of sweat. Intracutaneous skin tests with autologous sweat were performed on 50 AD patients and 24 control subjects. In skin biopsies, tryptase and PAR-2 were enzyme and immunohistochemically stained. The associations between skin test reactivity and sweat histamine concentration, tryptase or chymase activity levels, tryptase or PAR-2 expression and AD clinical severity or IgE levels were investigated. The wheal reactions in the intracutaneous tests with autologous sweat were positive, weakly positive and negative in 38, 34 and 28% of the AD patients, respectively, and in 4, 46 and 50% of the healthy controls, respectively (p = 0.008). In AD, the wheal reaction was associated significantly with clinical severity, serum total and specific IgE levels and sweat tryptase activity, but not with sweat histamine and chymase. In nonlesional AD skin, the percentage of PAR-2+ mast cells (MCs) or the number of tryptase+ MCs did not differ significantly between the intracutaneous test reactivity groups. Reactivity to autologous sweat correlates with the clinical severity of AD, and tryptase may be one of the factors involved in the sweat-induced wheal. © 2016 S. Karger AG, Basel.

Effect of activated autologous platelet-rich plasma on proliferation and osteogenic differentiation of human adipose-derived stem cells in vitro

PubMed Central

Xu, Fang-Tian; Li, Hong-Mian; Yin, Qing-Shui; Liang, Zhi-Jie; Huang, Min-Hong; Chi, Guang-Yi; Huang, Lu; Liu, Da-Lie; Nan, Hua

2015-01-01

To investigate whether activated autologous platelet-rich plasma (PRP) can promote proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs) in vitro. hASCs were isolated from lipo-aspirates, and characterized by specific cell markers and multilineage differentiation capacity after culturing to the 3rd passage. PRP was collected and activated from human peripheral blood of the same patient. Cultured hASCs were treated with normal osteogenic inductive media alone (group A, control) or osteogenic inductive media plus 5%, 10%, 20%, 40%PRP (group B, C, D, E, respectively). Cell proliferation was assessed by CCK-8 assay. mRNA expression of osteogenic marker genes including alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN) and core binding factor alpha 1 (Cbfa1) were determined by Real-Time Quantitative PCR Analysis (qPCR). Data revealed that different concentrations of activated autologous PRP significantly promoted hASCs growth in the proliferation phase compared to the without PRP group and resulted in a dose-response relationship. At 7-d and 14-d time point of the osteogenic induced stage, ALP activity in PRP groups gradually increased with the increasing of concentrations of PRP and showed that dose-response relationship. At 21-d time point of the osteogenic induced stage, PRP groups make much more mineralization and mRNA relative expression of ALP, OPN, OCN and Cbfa1 than that without PRP groups and show that dose-response relationship. This study indicated that different concentrations of activated autologous PRP can promote cell proliferation at earlier stage and promote osteogenic differentiation at later stage of hASCs in vitro. Moreover, it displayed a dose-dependent effect of activated autologous PRP on cell proliferation and osteogenic differentiation of hASCs in vitro. PMID:25901195

Use of autologous platelet rich plasma (PRP) in stopping massive hemoptysis at the Lung Center of the Philippines: a pilot study.

PubMed

Sarmiento, Armand Gregorio C; Danguilan, Jose Luis J; Mariano, Zenaida M; Barzaga, Maria Teresa A

2017-01-01

The purpose of this study is to determine the effect of using autologous platelet rich plasma (PRP) in patients having massive hemoptysis within a period of one week. This is a prospective cohort study involving 20 consecutive patients admitted who met the criteria for massive hemoptysis from July to October 2011. After stabilizing the patient, fiberoptic bronchoscopy (FOB) was performed for localization of bleeding within 6 hours from diagnosis. A 50mL of blood was extracted from the patient whom was to be used for autologous PRP concentrate. After identifying the anatomic site of bleeding, autologous PRP concentrate was instilled on the affected bronchus and was allowed to stay for 5 minutes after instillation. Patients were then monitored from the time the bleeding stopped in the first 24 hours, 2 days and 7 days respectively. Mean age of the study population with massive hemoptysis was 47 years old (SD 17.3). Majority of cases were male 18 out of 20 (90%) and smokers 14 (70%) with a normal BMI (75%). Identification of bleeding site was more commonly seen on the right upper lobe 9 out of 20 (45%). Overall, 14 out of 20 patients (70%) were reported to have stopped bleeding immediately. Subsequent hospital days showed that 8 out of 20 patients (40%) had no hemoptysis. However, one [1] post-tuberculosis (TB) bronchiectatic patient had recurrence of massive hemoptysis, approximately 250 mL per expectorate, expired within the 7 days observation and one patient had lobectomy on the 2nd day. The rest had non-massive hemoptysis wherein their expectorations were only streaks of blood. Moreover, there was one [1] patient who had recurrence of massive hemoptysis 1 week after autologous PRP infusion and was eventually intubated. Majority of the subjects, eleven [11] were diagnosed to have post-TB bronchiectasis. The rest of the patients were worked-up prior to operation. Overall, it was observed that the use of autologous PRP was able to stop bleeding in 40% of the study

Use of autologous platelet rich plasma (PRP) in stopping massive hemoptysis at the Lung Center of the Philippines: a pilot study

PubMed Central

Danguilan, Jose Luis J.; Mariano, Zenaida M.; Barzaga, Maria Teresa A.

2017-01-01

Background The purpose of this study is to determine the effect of using autologous platelet rich plasma (PRP) in patients having massive hemoptysis within a period of one week. Methods This is a prospective cohort study involving 20 consecutive patients admitted who met the criteria for massive hemoptysis from July to October 2011. After stabilizing the patient, fiberoptic bronchoscopy (FOB) was performed for localization of bleeding within 6 hours from diagnosis. A 50mL of blood was extracted from the patient whom was to be used for autologous PRP concentrate. After identifying the anatomic site of bleeding, autologous PRP concentrate was instilled on the affected bronchus and was allowed to stay for 5 minutes after instillation. Patients were then monitored from the time the bleeding stopped in the first 24 hours, 2 days and 7 days respectively. Results Mean age of the study population with massive hemoptysis was 47 years old (SD 17.3). Majority of cases were male 18 out of 20 (90%) and smokers 14 (70%) with a normal BMI (75%). Identification of bleeding site was more commonly seen on the right upper lobe 9 out of 20 (45%). Overall, 14 out of 20 patients (70%) were reported to have stopped bleeding immediately. Subsequent hospital days showed that 8 out of 20 patients (40%) had no hemoptysis. However, one [1] post-tuberculosis (TB) bronchiectatic patient had recurrence of massive hemoptysis, approximately 250 mL per expectorate, expired within the 7 days observation and one patient had lobectomy on the 2nd day. The rest had non-massive hemoptysis wherein their expectorations were only streaks of blood. Moreover, there was one [1] patient who had recurrence of massive hemoptysis 1 week after autologous PRP infusion and was eventually intubated. Majority of the subjects, eleven [11] were diagnosed to have post-TB bronchiectasis. The rest of the patients were worked-up prior to operation. Conclusions Overall, it was observed that the use of autologous PRP was able

Accelerated removal of antibody-coated red blood cells from the circulation is accurately tracked by a biotin label

PubMed Central

Mock, Donald M.; Lankford, Gary L.; Matthews, Nell I.; Burmeister, Leon F.; Kahn, Daniel; Widness, John A.; Strauss, Ronald G.

2013-01-01

BACKGROUND Safe, accurate methods to reliably measure circulating red blood cell (RBC) kinetics are critical tools to investigate pathophysiology and therapy of anemia, including hemolytic anemias. This study documents the ability of a method using biotin-labeled RBCs (BioRBCs) to measure RBC survival (RCS) shortened by coating with a highly purified monomeric immunoglobulin G antibody to D antigen. STUDY DESIGN AND METHODS Autologous RBCs from 10 healthy D+ subjects were labeled with either biotin or 51Cr (reference method), coated (opsonized) either lightly (n = 4) or heavily (n = 6) with anti-D, and transfused. RCS was determined for BioRBCs and for 51Cr independently as assessed by three variables: 1) posttransfusion recovery at 24 hours (PTR24) for short-term RCS; 2) time to 50% decrease of the label (T50), and 3) mean potential life span (MPL) for long-term RCS. RESULTS BioRBCs tracked both normal and shortened RCS accurately relative to 51Cr. For lightly coated RBCs, mean PTR24, T50, and MPL results were not different between BioRBCs and 51Cr. For heavily coated RBCs, both short-term and long-term RCS were shortened by approximately 17 and 50%, respectively. Mean PTR24 by BioRBCs (84 ± 18%) was not different from 51Cr (81 ± 10%); mean T50 by BioRBCs (23 ± 17 days) was not different from 51Cr (22 ± 18 days). CONCLUSION RCS shortened by coating with anti-D can be accurately measured by BioRBCs. We speculate that BioRBCs will be useful for studying RCS in conditions involving accelerated removal of RBCs including allo- and autoimmune hemolytic anemias. PMID:22023312

A comparison of free autologous breast reconstruction with and without the use of laser-assisted indocyanine green angiography: a cost-effectiveness analysis.

PubMed

Chatterjee, Abhishek; Krishnan, Naveen M; Van Vliet, Michael M; Powell, Stephen G; Rosen, Joseph M; Ridgway, Emily B

2013-05-01

Laser-assisted indocyanine green angiography is a U.S. Food and Drug Administration-approved technology used to assess tissue viability and perfusion. Its use in plastic and reconstructive surgery to assess flap perfusion in autologous breast reconstruction is relatively new. There have been no previous studies evaluating the cost-effectiveness of this new technology compared with the current practice of clinical judgment in evaluating tissue perfusion and viability in free autologous breast reconstruction in patients who have undergone mastectomy. A comprehensive literature review was performed to identify the complication rate of the most common complications with and without laser-assisted indocyanine green angiography in free autologous breast reconstruction after mastectomy. These probabilities were combined with Medicare Current Procedural Terminology provider reimbursement codes (cost) and utility estimates for common complications from a survey of 10 plastic surgeons to fit into a decision model to evaluate the cost-effectiveness of laser-assisted indocyanine green angiography. The decision model revealed a baseline cost difference of $773.66 and a 0.22 difference in the quality-adjusted life-years, yielding an incremental cost-utility ratio of $3516.64 per quality-adjusted life year favoring laser-assisted indocyanine green angiography. Sensitivity analysis showed that using laser-assisted indocyanine green angiography was more cost-effective when the complication rate without using laser-assisted indocyanine green angiography (clinical judgment alone) was 4 percent or higher. The authors' study demonstrates that laser-assisted indocyanine green angiography is a cost-effective technology under the most stringent acceptable thresholds when used in immediate free autologous breast reconstruction.

Treatment of pressure ulcers with autologous bone marrow nuclear cells in patients with spinal cord injury

PubMed Central

Sarasúa, J González; López, S Pérez; Viejo, M Álvarez; Basterrechea, M Pérez; Rodríguez, A Fernández; Gutiérrez, A Ferrero; Gala, J García; Menéndez, Y Menéndez; Augusto, D Escudero; Arias, A Pérez; Hernández, J Otero

2011-01-01

Context Pressure ulcers are especially difficult to treat in patients with spinal cord injury (SCI) and recurrence rates are high. Prompted by encouraging results obtained using bone marrow stem cells to treat several diseases including chronic wounds, this study examines the use of autologous stem cells from bone marrow to promote the healing of pressure ulcers in patients with SCI. Objective To obtain preliminary data on the use of bone marrow mononuclear cells (BM-MNCs) to treat pressure ulcers in terms of clinical outcome, procedure safety, and treatment time. Participants Twenty-two patients with SCI (19 men, 3 women; mean age 56.41 years) with single type IV pressure ulcers of more than 4 months duration. Interventions By minimally invasive surgery, the ulcers were debrided and treated with BM-MNCs obtained by Ficoll density gradient separation of autologous bone marrow aspirates drawn from the iliac crest. Results In 19 patients (86.36%), the pressure ulcers treated with BM-MNCs had fully healed after a mean time of 21 days. The number of MNCs isolated was patient dependent, although similar clinical outcomes were observed in each case. Compared to conventional surgical treatment, mean intra-hospital stay was reduced from 85.16 to 43.06 days. Following treatment, 5 minutes of daily wound care was required per patient compared to 20 minutes for conventional surgery. During a mean follow-up of 19 months, none of the resolved ulcers recurred. Conclusions Our data indicate that cell therapy using autologous BM-MNCs could be an option to treat type IV pressure ulcers in patients with SCI, avoiding major surgical intervention. PMID:21756569

Pure Red Cell Aplasia due to B19 Parvovirus Infection after Autologous Stem Cell Transplantation

PubMed Central

Tsirigotis, Panagiotis; Girkas, Konstantinos; Economopoulou, Christina; Bouchla, Anthoula; Papanicolaou, Nikolaos; Economopoulou, Panagiota; Papageorgiou, Sotirios; Pappa, Vassiliki; Dervenoulas, John

2011-01-01

Parvovirus B19 is recognized as a rare cause of pure red cell aplasia (PRCA) in allogeneic stem cell (SCT) and solid organ transplant patients. We report a patient with Hodgkin's disease who developed PRCA due to parvovirus B19 after autologous SCT and who had an excellent response after treatment with gamma-globulin. PMID:23198254

Autologous blood injection for treatment of chronic recurrent TMJ dislocation: is it successful? Is it safe enough? A systematic review.

PubMed

Varedi, Payam; Bohluli, Behnam

2015-09-01

The purpose of this article is to review the English literature about the efficacy and safety of autologous blood injection in treating patients suffering from chronic recurrent temporomandibular joint dislocation. In this article, we highlight the key trials and recent directions about this modality and discuss about the mechanism, advantages, and disadvantages of this approach. A literature search was performed using PubMed, Medline, and Ovid Medline databases to identify articles reporting on the injection of autologous blood for treatment of chronic recurrent dislocation of temporomandibular joint. Other references cited in the retrieved reports, as well as the "related articles" tool in PubMed Medline, were also checked to improve the search and, if relevant, were included in the study. The search was restricted to articles published in the English language. Seven studies meeting the inclusion criteria were reviewed. The selected articles included four prospective clinical trials and three case report articles. There are a few articles about the clinical use of autologous blood for treating patients with chronic recurrent temporomandibular joint dislocation. Reviewing of the literature shows that there are successful results about this modality, but there are still some concerns about it in terms of the effect of the injected blood on the articular cartilage and formation of fibrous or bony ankylosis.

A phase I/II trial of oxidized autologous tumor vaccines during the "watch and wait" phase of chronic lymphocytic leukemia.

PubMed

Spaner, David E; Hammond, Caitlin; Mena, Jenny; Foden, Cindy; Deabreu, Andrea

2005-07-01

Based on their activity in patients with advanced stage chronic lymphocytic leukemia (CLL), a phase I/II study was designed to evaluate the feasibility, safety, and efficacy of autologous vaccines made from oxidized tumor cells in patients with earlier stage CLL, and to determine an optimal schedule of injections. Eighteen patients (at risk for disease progression and with white blood cell counts between 15 and 100 x 10(6) cells/ml) were injected intramuscularly with 10 ml of oxidized autologous blood (composed mainly of CLL cells) either 12 times over 6 weeks (group 1), 12 times over 16 days (group 2), or 4 times over 6 weeks (group 3). Fourteen out of eighteen patients had Rai stage 0-II disease, while 4/18 had stage III-IV disease but did not require conventional treatment. Partial clinical responses, associated with enhanced anti-tumor T cell activity in vitro, were observed in 5/18 patients of whom three were in group 2. Stable disease was observed in six patients while disease progression appeared not to be affected in the remaining patients. Toxicity was minimal. Vaccination with oxidized autologous tumor cells appears worthy of further investigation and may be a potential alternative to a "watch and wait" strategy for selected CLL patients.

GEO Label: User and Producer Perspectives on a Label for Geospatial Data

NASA Astrophysics Data System (ADS)

Lush, V.; Lumsden, J.; Masó, J.; Díaz, P.; McCallum, I.

2012-04-01

One of the aims of the Science and Technology Committee (STC) of the Group on Earth Observations (GEO) was to establish a GEO Label- a label to certify geospatial datasets and their quality. As proposed, the GEO Label will be used as a value indicator for geospatial data and datasets accessible through the Global Earth Observation System of Systems (GEOSS). It is suggested that the development of such a label will significantly improve user recognition of the quality of geospatial datasets and that its use will help promote trust in datasets that carry the established GEO Label. Furthermore, the GEO Label is seen as an incentive to data providers. At the moment GEOSS contains a large amount of data and is constantly growing. Taking this into account, a GEO Label could assist in searching by providing users with visual cues of dataset quality and possibly relevance; a GEO Label could effectively stand as a decision support mechanism for dataset selection. Currently our project - GeoViQua, - together with EGIDA and ID-03 is undertaking research to define and evaluate the concept of a GEO Label. The development and evaluation process will be carried out in three phases. In phase I we have conducted an online survey (GEO Label Questionnaire) to identify the initial user and producer views on a GEO Label or its potential role. In phase II we will conduct a further study presenting some GEO Label examples that will be based on Phase I. We will elicit feedback on these examples under controlled conditions. In phase III we will create physical prototypes which will be used in a human subject study. The most successful prototypes will then be put forward as potential GEO Label options. At the moment we are in phase I, where we developed an online questionnaire to collect the initial GEO Label requirements and to identify the role that a GEO Label should serve from the user and producer standpoint. The GEO Label Questionnaire consists of generic questions to identify whether

Immediate autologous breast reconstruction after neoadjuvant chemoradiotherapy for breast cancer: initial results of the first 29 patients.

PubMed

Grinsell, Damien; Pitcher, Meron; Wong, Shirley; Guerrieri, Mario; Nielsen, Hans H M

2018-03-01

Breast reconstruction after mastectomy in the treatment of locally advanced breast cancer is often done in stages and before radiotherapy. We have previously published an algorithm for immediate free autologous reconstruction after neoadjuvant chemotherapy and preoperative radiotherapy. This protocol was designed to provide a shorter and simpler reconstructive path whilst improving cosmesis and maintaining oncological efficiency. A total of 29 patients were included and underwent surgery for 30 cancers by the first author between 2010 and September 2015. Data were prospectively entered into a database and analysed for tumour size, chemotherapeutic response, lymph node involvement, surgical complications and tumour recurrence. The mean age was 55 ± 7 years. Eighty percent of patients had either a partial or complete chemotherapeutic response defined as >25% decrease in tumour size. Twenty-eight patients had free abdominal tissue transfer. One patient was excluded due to advanced disease. There were no take-backs due to microsurgical issues. One patient was reoperated on for a haematoma. Four patients had recurrent cancer during follow-up, three of whom are deceased. Many, but not all, breast reconstructive surgeons consider autologous reconstruction as the 'gold' standard in the presence of radiotherapy. Rearranging the order of radiotherapy and surgery means operating in a recently irradiated field. We believe the surgical challenges are outweighed by a shorter and simpler reconstructive journey that additionally results in a better cosmesis. It is possible to perform immediate free autologous reconstruction after neoadjuvant chemotherapy and preoperative radiotherapy with excellent results and at least equivalent oncological efficacy. © 2017 Royal Australasian College of Surgeons.

Beneficial Effects of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Naturally Occurring Tendinopathy

PubMed Central

Smith, Roger Kenneth Whealands; Werling, Natalie Jayne; Dakin, Stephanie Georgina; Alam, Rafiqul; Goodship, Allen E.; Dudhia, Jayesh

2013-01-01

Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities to human tendinopathy making it an ideal large animal model for human disease. Regenerative approaches are increasingly used to improve outcome involving mesenchymal stem cells (MSCs), supported by clinical data where injection of autologous bone marrow derived MSCs (BM-MSCs) suspended in marrow supernatant into injured tendons has halved the re-injury rate in racehorses. We hypothesized that stem cell therapy induces a matrix more closely resembling normal tendon than the fibrous scar tissue formed by natural repair. Twelve horses with career-ending naturally-occurring superficial digital flexor tendon injury were allocated randomly to treatment and control groups. 1X107 autologous BM-MSCs suspended in 2 ml of marrow supernatant were implanted into the damaged tendon of the treated group. The control group received the same volume of saline. Following a 6 month exercise programme horses were euthanized and tendons assessed for structural stiffness by non-destructive mechanical testing and for morphological and molecular composition. BM-MSC treated tendons exhibited statistically significant improvements in key parameters compared to saline-injected control tendons towards that of normal tendons and those in the contralateral limbs. Specifically, treated tendons had lower structural stiffness (p<0.05) although no significant difference in calculated modulus of elasticity, lower (improved) histological scoring of organisation (p<0.003) and crimp pattern (p<0.05), lower cellularity (p<0.007), DNA content (p<0.05), vascularity (p<0.03), water content (p<0.05), GAG content (p<0.05), and MMP-13 activity (p<0.02). Treatment with autologous MSCs in marrow supernatant therefore provides significant benefits compared to untreated tendon repair in

Penile enhancement using autologous tissue engineering with biodegradable scaffold: a clinical and histomorphometric study.

PubMed

Perovic, Sava V; Sansalone, Salvatore; Djinovic, Rados; Ferlosio, Amedeo; Vespasiani, Giuseppe; Orlandi, Augusto

2010-09-01

Autologous tissue engineering with biodegradable scaffolds is a new treatment option for real penile girth enhancement. The aim of this article is to evaluate tissue remodeling after penile girth enhancement using this technique. Between June 2005 and May 2007, a group of 12 patients underwent repeated penile widening using biodegradable scaffolds enriched with expanded autologous scrotal dartos cells. Clinical monitoring was parallel to histological investigation of tissue remodeling. During second surgical procedure, biopsies were obtained 10-14 months after first surgery (mean 12 months, N=6) and compared with those obtained after 22-24 months (mean 23 months, N=6), and control biopsies from patients who underwent circumcision (N=5). Blind evaluation of histomorphometrical and immunohistochemical finding was performed in paraffin sections. Penile girth gain in a flaccid state ranged between 1.5 and 3.8 cm (mean 2.1 ± 0.28 cm) and in full erection between 1.2 and 4 cm (mean 1.9 ± 0.28 cm). Patients' satisfaction, defined by a questionnaire, was good (25%) and very good (75%). In biopsies obtained 10-14 months after first surgery, highly vascularized loose tissue with collagen deposition associated with small foci of mild chronic and granulomatous inflammation surrounding residual amorphous material was observed. Fibroblast-like hyperplasia and small vessel neoangiogenesis occurred intimately associated with the progressive growth of vascular-like structures from accumulation of CD34 and alpha-smooth muscle actin-positive cells surrounding residual scaffold-like amorphous material. Capillary neoangiogenesis occurred inside residual amorphous material. In biopsies obtained after 22-24 months, inflammation almost disappeared and tissue closely resembled that of the dartos fascia of control group. Autologous tissue engineering using expanded scrotal dartos cells with biodegradable scaffolds is a new and promising method for penile widening that generates

Allelic distribution of human leucocyte antigen in historical and recently diagnosed tuberculosis patients in Southern Italy.

PubMed

Ruggiero, Giuseppina; Cosentini, Elena; Zanzi, Delia; Sanna, Veronica; Terrazzano, Giuseppe; Matarese, Giuseppe; Sanduzzi, Alessandro; Perna, Francesco; Zappacosta, Serafino

2004-03-01

This study addresses the analysis of the human leucocyte antigen (HLA) allele distribution in 54 historical and in 68 recently diagnosed tuberculosis (TB) patients. The historical cohort was characterized by the presence of large fibrocavernous lesions effectively treated with therapeutic pneumothorax during the period 1950-55. Patients and healthy controls enrolled in the study were from the Campania region of southern Italy. No significant association between HLA alleles and TB in the population of recently diagnosed TB patients was observed. On the contrary, among the historical TB patients there was a strong association with an increased frequency of the HLA-DR4 allele alone and/or in the presence of the HLA-B14 allele (P = 0.000004; Pc = 0.0008), as well as with a decreased frequency of the HLA-A2+,-B14-,DR4- allele association (P = 0.00005; Pc = 0.01). In order to exclude any interference from age-related factors, these results were confirmed by comparing the historical cohort of TB patients with an age-matched healthy control population of the same ethnic origin (P = 0.00004; Pc = 0.008; and P = 0.0001; and Pc = 0.02, respectively).

Dynamic map labeling.

PubMed

Been, Ken; Daiches, Eli; Yap, Chee

2006-01-01

We address the problem of filtering, selecting and placing labels on a dynamic map, which is characterized by continuous zooming and panning capabilities. This consists of two interrelated issues. The first is to avoid label popping and other artifacts that cause confusion and interrupt navigation, and the second is to label at interactive speed. In most formulations the static map labeling problem is NP-hard, and a fast approximation might have O(nlogn) complexity. Even this is too slow during interaction, when the number of labels shown can be several orders of magnitude less than the number in the map. In this paper we introduce a set of desiderata for "consistent" dynamic map labeling, which has qualities desirable for navigation. We develop a new framework for dynamic labeling that achieves the desiderata and allows for fast interactive display by moving all of the selection and placement decisions into the preprocessing phase. This framework is general enough to accommodate a variety of selection and placement algorithms. It does not appear possible to achieve our desiderata using previous frameworks. Prior to this paper, there were no formal models of dynamic maps or of dynamic labels; our paper introduces both. We formulate a general optimization problem for dynamic map labeling and give a solution to a simple version of the problem. The simple version is based on label priorities and a versatile and intuitive class of dynamic label placements we call "invariant point placements". Despite these restrictions, our approach gives a useful and practical solution. Our implementation is incorporated into the G-Vis system which is a full-detail dynamic map of the continental USA. This demo is available through any browser.

Comparison of the Fenwal Amicus and Fresenius Com.Tec cell separators for autologous peripheral blood progenitor cell collection.

PubMed

Altuntas, Fevzi; Kocyigit, Ismail; Ozturk, Ahmet; Kaynar, Leylagul; Sari, Ismail; Oztekin, Mehmet; Solmaz, Musa; Eser, Bulent; Cetin, Mustafa; Unal, Ali

2007-04-01

Peripheral blood progenitor cells (PBPC) are commonly used as a stem cell source for autologous transplantation. This study was undertaken to evaluate blood cell separators with respect to separation results and content of the harvest. Forty autologous PBPC collections in patients with hematological malignancies were performed with either the Amicus or the COM.TEC cell separators. The median product volume was lower with the Amicus compared to the COM.TEC (125 mL vs. 300 mL; p < 0.001). There was no statistically significant difference in the median number of CD34+ cell/kg in product between the Amicus and the COM.TEC (3.0 x 10(6) vs. 4.1 x 10(6); p = 0.129). There was a statistically higher mean volume of ACD used in collections on the Amicus compared to the COM.TEC (1040 +/- 241 mL vs. 868 +/- 176 mL; p = 0.019). There was a statistical difference in platelet (PLT) contamination of the products between the Amicus and the COM.TEC (0.3 x 10(11) vs. 1.1 x 10(11); p < 0.001). The median % decrease in PB PLT count was statistically higher in the COM.TEC compared to the Amicus instruments (18.5% vs. 9.5%; p = 0.028). In conclusion, both instruments collected PBPCs efficiently. However, Amicus has the advantage of lower PLT contamination in the product, and less decrease in PB platelet count with lower product volume in autologous setting.

Autologous microtia reconstruction combined with ancillary procedures: a comprehensive reconstructive approach.

PubMed

Cugno, S; Farhadieh, R D; Bulstrode, N W

2013-11-01

Autologous microtia reconstruction is generally performed in two stages. The second stage presents a unique opportunity to carry out other complementary procedures. The present study describes our approach to microtia reconstruction, wherein the second stage of reconstruction is combined with final refinements to the ear construct and/or additional procedures to enhance facial contour and symmetry. Retrospective analysis of patients who underwent two-stage microtia reconstruction by a single surgeon (NWB) was conducted in order to ascertain those that had ancillary procedures at the time of the second stage. Patient and operative details were collected. Thirty-four patients (male, 15, median age and age range at second stage, 11 and 10-18 years, respectively) who had complementary procedures executed during the second stage of auricular reconstruction were identified. Collectively, these included centralizing genioplasty (n = 1), fat transfer (n = 22), ear piercing (n = 7), and contralateral prominauris correction (n = 7). Six patients had correction for unilateral isolated microtia and in the remaining 28 patients, auricular reconstruction for microtia associated with a named syndrome. All patients reported a high rate of satisfaction with the result achieved and the majority (85%) reported no perceived need for additional surgical refinements to the ear or procedure(s) to achieve further facial symmetry. No peri- or post-operative complications were noted. Combining the final stage of autologous microtia reconstruction with other ancillary procedures affords a superior aesthetic outcome and decreased patient morbidity. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. All rights reserved.

Do autologous peripheral blood cell transplants provide more than hematopoietic recovery?

PubMed

Kessinger, A

1995-07-01

Bone marrow damage caused by myeloablative radiation therapy and/or chemotherapy can be repaired by intravenously infusing viable stem/progenitor cells collected from either blood or bone marrow. The hematopoietic graft product contains both stem/progenitor cells and populations of hematopoietic and nonhematopoietic (accessory) cells. The frequency of accessory cell types varies with the source of the graft product; marrow or blood. Reinfusion of these accessory cells causes effects other than the hematopoietic restoration provided by the stem/progenitor cells such as graft versus host disease and graft versus leukemia effect after allogeneic transplants. Effects of infused accessory cells in the autologous setting are less well studied and could provide ancillary advantages and/or disadvantages to the patient. Do these additional effects actually occur, and, if they do, are they more likely to appear following peripheral blood cell transplants (PBCT) or after autologous bone marrow transplants (AMBT)? Preliminary data are beginning to accumulate which suggest that reinfusion of occult tumor cells is less likely with PBCT, that immune reconstitution is different depending on the source of the autograft and that, for certain diseases, patient event-free survival following PBCT rather than ABMT may be better. However, infusion of occult tumor cells may result in re-establishment of the malignancy. If the accessory cells (including potential occult tumor cells) are eliminated from the product before transplant, will the patient have a better clinical outcome, or would benefits provided by infused accessory cells outweigh the risks of infused occult tumor cells? These controversial issues are in the very early stages of investigation.

Use of autologous platelet-rich plasma in complete cleft palate repair.

PubMed

El-Anwar, Mohammad Waheed; Nofal, Ahmed Abdel Fattah; Khalifa, Mohamed; Quriba, Amal Saeed

2016-07-01

Evaluate the effect of topical application of autologous platelet-rich plasma (PRP) in primary repair of complete cleft palate and then compare the result with another group of patients using the same surgical technique, without application of PRP with regard to the incidence of oronasal fistula, velopharyngeal closure, and grade of nasality. Case control study. This study was carried on 44 children with complete cleft palate with age range from 12 to 23 months. The children were divided into two age- and gender-matched groups: All children were subjected to the same technique of V-Y pushback repair of the complete cleft palate. In group A (22 children), the PRP prepared from the patient was topically applied between the nasal and oral mucosa layer during palatoplasty, whereas in group B (22 children) the PRP was not applied. All cases were recovered smoothly without problems. In group A, no oronasal fistula was reported, whereas in group B three patients (13.6%) had postoperative fistulae and two patients (9.1%) needed revision palatoplasty. At 6 months postoperative assessment, group A (with PRP application) showed significantly better grade of nasality (P = 0.024) and better endoscopic velopharyngeal closure (P = 0.016) than group B. Usage of autologous PRP in complete cleft palate repair is simple; effective; can decrease the incidence of oronasal fistula; and also significantly improves the grade of nasality and velopharyngeal closure, which decreases the need of further surgical intervention in cleft palate patients. 3b. Laryngoscope, 126:1524-1528, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

A New Technique for the Treatment of Lumbar Facet Joint Syndrome Using Intra-articular Injection with Autologous Platelet Rich Plasma.

PubMed

Wu, Jiuping; Du, Zhenwu; Lv, Yang; Zhang, Jun; Xiong, Wei; Wang, Ruiqiang; Liu, Rui; Zhang, Guizhen; Liu, Qinyi

2016-01-01

Lumbar facet joint syndrome is currently suggested to be a main source of axial low back pain, and a large portion of axial low back pain is caused by disorders in lumbar facet joints. Intra-articular injection is one of the most common treatment methods in the early clinical application. Therefore, we attempt to seek a new injectable material, autologous platelet rich plasma (PRP), to treat lumbar facet syndrome, as well as to assess its therapeutic effectiveness and safety. A prospective clinic evaluation. The outpatient clinic of a single academic medical center. Total 19 patients with lumbar facet joint syndrome (8 men, 11 women; mean ages: 52.53 ± 6.79 years, range: 38 - 62 years) were enrolled to receive lumbar facet joint injection with autologous PRP under x-ray fluoroscopic control. Patients were followed up immediately, at one week, one month, 2 months, and 3 months following treatment, and the elements of this analysis included low back pain visual analogue scale (VAS) at rest and during flexion, Roland-Morris Disability Questionnaire (RMQ), Oswestry Disability Index (ODI), and modified MacNab criteria for the pain relief. All the 19 patients completed the intra-articular injections with autologous PRP successfully. At one week after treatment, low back pain reduced significantly compared with prior to treatment both at rest and during flexion. The outcomes were assessed as "good" or "excellent" for 9 patients (47.37%) immediately after treatment, 14 patients (73.68%) at one week, 15 patients (78.95%) at one month, 15 patients (78.95%) at 2 months, and 15 patients (78.95%) at 3 months. Statistically significant differences were observed based on RMQ and a more than 10% improvement in lumbar functional capacity was observed based on ODI between pre-treatment and post-treatment. In addition, there were no severe relevant complications during the whole process of injection and follow-up period. A control group and the curative effect observations with

Future Economics of Liver Transplantation: A 20-Year Cost Modeling Forecast and the Prospect of Bioengineering Autologous Liver Grafts

PubMed Central

Habka, Dany; Mann, David; Landes, Ronald; Soto-Gutierrez, Alejandro

2015-01-01

During the past 20 years liver transplantation has become the definitive treatment for most severe types of liver failure and hepatocellular carcinoma, in both children and adults. In the U.S., roughly 16,000 individuals are on the liver transplant waiting list. Only 38% of them will receive a transplant due to the organ shortage. This paper explores another option: bioengineering an autologous liver graft. We developed a 20-year model projecting future demand for liver transplants, along with costs based on current technology. We compared these cost projections against projected costs to bioengineer autologous liver grafts. The model was divided into: 1) the epidemiology model forecasting the number of wait-listed patients, operated patients and postoperative patients; and 2) the treatment model forecasting costs (pre-transplant-related costs; transplant (admission)-related costs; and 10-year post-transplant-related costs) during the simulation period. The patient population was categorized using the Model for End-Stage Liver Disease score. The number of patients on the waiting list was projected to increase 23% over 20 years while the weighted average treatment costs in the pre-liver transplantation phase were forecast to increase 83% in Year 20. Projected demand for livers will increase 10% in 10 years and 23% in 20 years. Total costs of liver transplantation are forecast to increase 33% in 10 years and 81% in 20 years. By comparison, the projected cost to bioengineer autologous liver grafts is $9.7M based on current catalog prices for iPS-derived liver cells. The model projects a persistent increase in need and cost of donor livers over the next 20 years that’s constrained by a limited supply of donor livers. The number of patients who die while on the waiting list will reflect this ever-growing disparity. Currently, bioengineering autologous liver grafts is cost prohibitive. However, costs will decline rapidly with the introduction of new manufacturing

Future Economics of Liver Transplantation: A 20-Year Cost Modeling Forecast and the Prospect of Bioengineering Autologous Liver Grafts.

PubMed

Habka, Dany; Mann, David; Landes, Ronald; Soto-Gutierrez, Alejandro

2015-01-01

During the past 20 years liver transplantation has become the definitive treatment for most severe types of liver failure and hepatocellular carcinoma, in both children and adults. In the U.S., roughly 16,000 individuals are on the liver transplant waiting list. Only 38% of them will receive a transplant due to the organ shortage. This paper explores another option: bioengineering an autologous liver graft. We developed a 20-year model projecting future demand for liver transplants, along with costs based on current technology. We compared these cost projections against projected costs to bioengineer autologous liver grafts. The model was divided into: 1) the epidemiology model forecasting the number of wait-listed patients, operated patients and postoperative patients; and 2) the treatment model forecasting costs (pre-transplant-related costs; transplant (admission)-related costs; and 10-year post-transplant-related costs) during the simulation period. The patient population was categorized using the Model for End-Stage Liver Disease score. The number of patients on the waiting list was projected to increase 23% over 20 years while the weighted average treatment costs in the pre-liver transplantation phase were forecast to increase 83% in Year 20. Projected demand for livers will increase 10% in 10 years and 23% in 20 years. Total costs of liver transplantation are forecast to increase 33% in 10 years and 81% in 20 years. By comparison, the projected cost to bioengineer autologous liver grafts is $9.7M based on current catalog prices for iPS-derived liver cells. The model projects a persistent increase in need and cost of donor livers over the next 20 years that's constrained by a limited supply of donor livers. The number of patients who die while on the waiting list will reflect this ever-growing disparity. Currently, bioengineering autologous liver grafts is cost prohibitive. However, costs will decline rapidly with the introduction of new manufacturing

Understanding Food Labels

MedlinePlus

... Healthy eating for girls Understanding food labels Understanding food labels There is lots of info on food ... need to avoid because of food allergies. Other food label terms top In addition to the Nutrition ...

78 FR 66826 - Prior Label Approval System: Generic Label Approval

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-07

... container of a misleading form or size.\\1\\ FSIS has interpreted these provisions as requiring that the...-evaluating-labeling . Labels submitted as an extraordinary circumstance are given the highest priority for... submissions to FSIS headquarters, thus increasing the availability of FSIS labeling staff. Upon publication of...

Autologous neurosensory retinal free patch transplantation for persistent full-thickness macular hole.

PubMed

De Giacinto, Chiara; D'Aloisio, Rossella; Cirigliano, Gabriella; Pastore, Marco Rocco; Tognetto, Daniele

2018-03-27

To evaluate anatomical and functional outcomes after autologous neurosensory retinal free patch (ANRFP) transplantation for persistent idiopathic full-thickness macular hole (iFTMH). A 65-year-old woman with persistent macular hole in her right eye after previous 27-gauge pars plana vitrectomy with internal limiting membrane peeling and long-acting gas tamponade underwent ANRFP transplantation. Before surgery, best corrected visual acuity in her right eye was 20/800. Optical coherence tomography (OCT) showed a 715-micron-diameter FTMH. To treat the persistent FTMH, a small autologous neurosensory retinal patch was transplanted and placed inside the macular hole under perfluorocarbon liquids (PFCL). PFCL-air exchange was performed, and long-acting gas tamponade was carried out. Clinical features of the macular area, visual acuity (VA), fundus autofluorescence, microperimetry and OCT were recorded during the 10-month follow-up. The macular hole appeared successfully closed with retinal patch stable and well plugged into the hole during the whole follow-up. VA improved to 20/100 and microperimetry revealed an increase in mean retinal sensitivity from 14.7 dB at 1 month to 15.6 dB at 10 months postoperatively. OCT showed a well-distinguishable retinal patch into the hole 1 month after surgery and a completely integrated retinal patch between the retinal layers 10 months postoperatively. No intra- and postoperative complications were noticed. ANRFP transplantation may represent an innovative technique for persistent iFTMH treatment.