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Sample records for autologous bone marrow

  1. Pituitary abscess after autologous bone marrow transplantation.

    PubMed

    Leff, R S; Martino, R L; Pollock, W J; Knight, W A

    1989-05-01

    The first case of pituitary abscess arising in a patient during recovery from autologous bone marrow transplantation is reported. A 31-year-old man with a 9 month history of T-cell lymphoma died suddenly more than 60 days after successful treatment with high-dose cyclophosphamide, total body irradiation, and autologous bone marrow infusion. Autopsy revealed a pituitary abscess associated with clinically silent sphenoid sinusitis. Unique aspects of this case are presented and clinical and pathologic features of pituitary abscess are reviewed. Although rare, pituitary abscess may complicate recovery from bone marrow transplantation.

  2. Long-term cryopreservation of bone marrow for autologous transplantation.

    PubMed

    Attarian, H; Feng, Z; Buckner, C D; MacLeod, B; Rowley, S D

    1996-03-01

    Little is known about the effect of long-term cryopreservation on the viability of hematopoietic stem cells (HSC) or on the success of autologous bone marrow transplantation. Although progenitor cell assays such as culture of CFU-GM after thawing can be predictive of engraftment, the most rigorous assay for the cryosurvival of HSC is engraftment after reinfusion of stem cells. We retrospectively evaluated the engraftment data for 36 patients with hematologic malignancies or solid tumors treated at the Fred Hutchinson Cancer Research Center between 1981 and 1993 who received bone marrows stored for 2 years or more. The median duration of cryopreservation for this study group was 2.7 years (range 2.0-7.8). Ninety-seven percent of patients in the study group achieved a granulocyte count of > or = 0.5 x 1.0(9)/1 at a median of 19 days (range 10-115) vs 86% of control group (selected by diagnosis and date of storage) at a median of 20 days (P = 0.14). Seventy percent of patients in the study group achieved a platelet count > or = 20 x 10(9)/1 at a median of 27 days (range 9-69) vs 74% of control group at a median of 23 days (P = 0.47). Also, samples of 28 marrows cryopreserved for a median of 4.4 years (range 2.0-7.8) were cultured to determine if a loss of hematopoietic progenitors relative to duration of storage could be detected. The storage length was not predictive for the quantity of colonies formed (P = 0.57 for BFU-E-derived colonies; P = 0.65 for CFU-GM-derived colonies). We found no consistent detrimental effect of long-term cryopreservation on the success rate of autologous bone marrow transplantation. This report confirms previous reports that marrow cells cryopreserved for several years are capable of engrafting. Therefore, bone marrow cells may be stored at an early appropriate time before the side-effects of multiple cycles of chemotherapy and radiotherapy on hematopoietic tissues are incurred.

  3. Bone marrow transplant

    MedlinePlus

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; ...

  4. [Suitability of autologous blood donation before bone marrow donation].

    PubMed

    Gouëzec, H; Ferré, N; Hervé, F; Lapart, C; Leberre, C; Bernard, M; Dauriac, C; Nimubona, S

    2015-06-01

    We assessed the benefit of predeposite autologous blood donation (PAD) before bone marrow (BM) donation on transfusion requirements, haemoglobin concentrations (Hb) and the occurrence of adverse events (AE). We collected data retrospectively from 50 donors of BM with PAD from 2010 to 2014. An autologous transfusion (AT) was given to 50% of the donors (group 1). In the group 2, the products from PAD were not used. The total volume median of marrow harvested was 17.7 mL/k (range 12.3-21.4) in the group 1 and 13.3 mL/k (8.6-22.6) in the group 2. The female ratio was higher in the group 1 (60%) than in the group 2 (16%). Bone marrow harvest led to a decline in Hb (from PAD to first day after BM donation) by 2.9 g/dL (1.5-5.5) in the group 1 and by 3.5 g/dL (1.2-5) in the group 2. The post-harvest Hb (D+1) median was identical in the two groups: 10.9 g/dL (7.6-13.5) in the group 1 versus 11.5 g/dL (9.3-13.4) in the group 2. Six AE were reported in each group. In the group with AE, the median weight was lower: 58 k (50-71) versus 75 k (52-110); and the median total volume of marrow harvested was higher: 20.1 mL/k (9.9-21.4) versus 14.3 mL/k (8.6-22.6). All post-harvest Hb were ≥ 7.6g/dL. This study shows the high loss of Hb after BM donation but not enough to prove a blood transfusion in BM donors with median age of 36 years (16-62) and without comorbidity. The occurrence of AE (25% of BM donors) justifies a careful surveillance after the BM donation. The PAD should not be routinely offered to bone marrow donors.

  5. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid.

    PubMed

    Ambrus, C M; Ambrus, J L

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colonyforming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls.

  6. Autologous Pancreatic Islet Transplantation in Human Bone Marrow

    PubMed Central

    Maffi, Paola; Balzano, Gianpaolo; Ponzoni, Maurilio; Nano, Rita; Sordi, Valeria; Melzi, Raffaella; Mercalli, Alessia; Scavini, Marina; Esposito, Antonio; Peccatori, Jacopo; Cantarelli, Elisa; Messina, Carlo; Bernardi, Massimo; Del Maschio, Alessandro; Staudacher, Carlo; Doglioni, Claudio; Ciceri, Fabio; Secchi, Antonio; Piemonti, Lorenzo

    2013-01-01

    The liver is the current site of choice for pancreatic islet transplantation, even though it is far from being ideal. We recently have shown in mice that the bone marrow (BM) may be a valid alternative to the liver, and here we report a pilot study to test feasibility and safety of BM as a site for islet transplantation in humans. Four patients who developed diabetes after total pancreatectomy were candidates for the autologous transplantation of pancreatic islet. Because the patients had contraindications for intraportal infusion, islets were infused in the BM. In all recipients, islets engrafted successfully as shown by measurable posttransplantation C-peptide levels and histopathological evidence of insulin-producing cells or molecular markers of endocrine tissue in BM biopsy samples analyzed during follow-up. Thus far, we have recorded no adverse events related to the infusion procedure or the presence of islets in the BM. Islet function was sustained for the maximum follow-up of 944 days. The encouraging results of this pilot study provide new perspectives in identifying alternative sites for islet infusion in patients with type 1 diabetes. Moreover, this is the first unequivocal example of successful engraftment of endocrine tissue in the BM in humans. PMID:23733196

  7. The effect of autologous bone marrow stromal cells differentiated on scaffolds for canine tibial bone reconstruction.

    PubMed

    Özdal-Kurt, F; Tuğlu, I; Vatansever, H S; Tong, S; Deliloğlu-Gürhan, S I

    2015-01-01

    Bone marrow contains mesenchymal stem cells that form many tissues. Various scaffolds are available for bone reconstruction by tissue engineering. Osteoblastic differentiated bone marrow stromal cells (BMSC) promote osteogenesis on scaffolds and stimulate bone regeneration. We investigated the use of cultured autologous BMSC on different scaffolds for healing defects in tibias of adult male canines. BMSC were isolated from canine humerus bone marrow, differentiated into osteoblasts in culture and loaded onto porous ceramic scaffolds including hydroxyapatite 1, hydroxyapatite gel and calcium phosphate. Osteoblast differentiation was verified by osteonectine and osteocalcine immunocytochemistry. The scaffolds with stromal cells were implanted in the tibial defect. Scaffolds without stromal cells were used as controls. Sections from the defects were processed for histological, ultrastructural, immunohistochemical and histomorphometric analyses to analyze the healing of the defects. BMSC were spread, allowed to proliferate and differentiate to osteoblasts as shown by alizarin red histochemistry, and osteocalcine and osteonectine immunostaining. Scanning electron microscopy showed that BMSC on the scaffolds were more active and adhesive to the calcium phosphate scaffold compared to the others. Macroscopic bone formation was observed in all groups, but scaffolds with stromal cells produced significantly better results. Bone healing occurred earlier and faster with stromal cells on the calcium phosphate scaffold and produced more callus compared to other scaffolds. Tissue healing and osteoblastic marker expression also were better with stromal cells on the scaffolds. Increased trabecula formation, cell density and decreased fibrosis were observed in the calcium phosphate scaffold with stromal cells. Autologous cultured stromal cells on the scaffolds were useful for healing of canine tibial bone defects. The calcium phosphate scaffold was the best for both cell

  8. Evaluation of autologous bone marrow in wound healing in animal model: a possible application of autologous stem cells.

    PubMed

    Akela, Ashok; Nandi, Samit Kumar; Banerjee, Dibyajyoti; Das, Partha; Roy, Subhasis; Joardar, Siddhartha Narayan; Mandal, Mohan; Das, Pradip Kumar; Pradhan, Nisith Ranjan

    2012-10-01

    A study was conducted to evaluate the potential of autologous bone marrow-derived cells in comparison with buffy coat of autologous blood for rapid cutaneous wound healing in rabbit model. Three square full-thickness skin excisional wounds were created in 15 selected experimental animals (rabbit) divided randomly into three groups. The wound was treated with autologous bone marrow cells in plasma (group 1), buffy coat of blood in plasma (group 2) and autologous plasma as control (group 3). Wounds were observed for 30 days for granulation tissue formation, biochemical, histomorphological and histochemical evaluation. In this study, granulation tissue appeared significantly lesser in wounds of group 3 animals followed by group 2 and 1 animals. Neovascularisation, granulation tissue formation, denser, thicker and better arranged collagen fibres, reticulin fibres and elastin fibres formation was more in group 1 as compared with other groups. It was concluded that the application of bone marrow-derived nucleated cells into the wound margins resulted in early and significantly faster rate of complete healing as compared with buffy coat of autologous blood and autologous plasma (control). This approach may be beneficial in various surface wounds that heal at a slower rate and recommended for healing of various complicated wound in future.

  9. Transcoronary sinus delivery of autologous bone marrow and angiogenesis in pig models with myocardial injury

    SciTech Connect

    Vicario, J.; Piva, J.; Pierini, A.; Ortega, H.H.; Canal, A.; Gerardo, L.; Pfeiffer, H.; Campos, C.; Fendrich, I.; Novero, R.; Monti, 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 the 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.

  10. Haemophilus influenzae type b (HIB)-conjugate immunization before bone marrow harvest in autologous bone marrow transplantation.

    PubMed

    Molrine, D C; Guinan, E C; Antin, J H; Wheeler, C; Parsons, S K; Weinstein, H J; McGarigle, C; Blanding, P; Phillips, N R; Ciamarra, A; George, S; Ambrosino, D M

    1996-06-01

    Immune reconstitution following autologous bone marrow transplantation (ABMT) is characterized by defects in B cell and T cell function and loss of specific antibody. In the late post-transplant period, patients are at risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We examined whether immunizing ABMT patients before bone marrow (BM) harvest enhanced the early recovery of specific antibody. Twelve patients were immunized before BM harvest with Haemophilus influenzae type b (HIB)-conjugate, tetanus toxoid and polysaccharide pneumococcal vaccines. Forty-one comparable ABMT patients not immunized prior to BM harvest were also studied. Following ABMT, both groups of patients were immunized with HIB-conjugate and tetanus toxoid vaccines at 3, 6, 12 and 24 months and with pneumococcal vaccine at 12 and 24 months. Patients immunized before BM harvest had higher HIB antibody concentrations during the first 2 years post-transplant, the differences reaching significance at 3 months (P = 0.0001) and following the 24-month dose (P = 0.048). Tetanus toxoid antibody concentrations were also significantly higher at 3 months (P = 0.001) and 6 months (P = 0.032) in patients immunized before BM harvest. There were no differences in pneumococcal antibody concentrations between the two groups. Immunization of patients before bone marrow harvest resulted in higher anti-HIB antibody concentrations following ABMT and may be an effective strategy to prevent infectious complications.

  11. Intra-arterial Autologous Bone Marrow Cell Transplantation in a Patient with Upper-extremity Critical Limb Ischemia

    SciTech Connect

    Madaric, Juraj; Klepanec, Andrej; Mistrik, Martin; Altaner, Cestmir; Vulev, Ivan

    2013-04-15

    Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

  12. Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis.

    PubMed

    Saito, Takafumi; Okumoto, Kazuo; Haga, Hiroaki; Nishise, Yuko; Ishii, Rika; Sato, Chikako; Watanabe, Hisayoshi; Okada, Akio; Ikeda, Motoki; Togashi, Hitoshi; Ishikawa, Tsuyoshi; Terai, Shuji; Sakaida, Isao; Kawata, Sumio

    2011-09-01

    The present study was conducted to evaluate the application and efficacy of autologous bone marrow infusion (ABMi) for improvement of liver function in patients with alcoholic liver cirrhosis (ALC). Five subjects and 5 control patients with ALC who had abstained from alcohol intake for 24 weeks before the study were enrolled. Autologous bone marrow cells were washed and injected intravenously, and the changes in serum liver function parameters, and the level of the type IV collagen 7S domain as a marker of fibrosis, were monitored for 24 weeks. The distribution of activated bone marrow was assessed by indium-111-chloride bone marrow scintigraphy. The number of cells infused was 8.0±7.3×10(9) (mean±standard error). The serum levels of albumin and total protein and the prothrombin time were significantly higher during the follow-up period after ABMi than during the observation period in treated patients, whereas no such changes were observed in the controls. In the patients who received ABMi, the Child-Pugh score decreased in all 3 who were classified as class B; the serum levels of type IV collagen 7S domain improved in 4 of the 5 patients; and bone marrow scintigraphy demonstrated an increase of indium-111-chloride uptake in 3 of the 4 patients tested. ABMi for patients with ALC helps improve liver function parameters in comparison with observation during abstinence and ameliorates the degree of fibrosis in terms of serum markers and bone marrow activation in most cases.

  13. In vitro growth and osteoblastic differentiation of human bone marrow stromal cells supported by autologous plasma.

    PubMed

    Schecroun, N; Delloye, Ch

    2004-08-01

    Autologous bone marrow stromal cells have been proposed as an adjuvant in the treatment of bone nonunion. This cell therapy requires the establishment of culture conditions that permit the rapid expansion of these cells ex vivo while retaining their potential for further differentiation. Several culture models have been proposed, all of them using fetal calf serum (FCS) as a source of growth factors. This is problematic for subsequent autologous implantation because of possible disease transmission. Here we report the establishment and characterization of a cell culture system in which standard FCS has been replaced by autologous plasma recovered from bone marrow (APM). Short-term cultures of human bone marrow stromal (HBMS) cells grown in mineralizing conditions with APM exhibited a significantly higher number of ALP-positive colonies than those grown with FCS, indicating an enhanced ability of APM to recruit osteoprogenitor cells for culture. Analyses of long-term cultures showed that the use of APM did not affect cell proliferation as cell number at confluence and proliferation rate were similar whether primary cultures had been maintained with APM or FCS. In first-passage cultures, an osteoblastic differentiation was observed in both cases as the cells expressed ALP and formed mineralized bone-like nodules. We noted that the age of donor had a negative effect on the number of osteoprogenitor cells recruited for culture. This effect had an impact on proliferation rate in primary cultures performed with APM, although the cell number obtained after expansion remained independent of age. Our study shows that proliferative capacity and osteoblastic differentiation potential of HBMS cells are maintained when cultured with APM. Thus, this cell culture system could provide a new and safer tool to elaborate an autologous cell therapy designed to enhance osteogenesis.

  14. 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

  15. Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow.

    PubMed

    den Boer, Frank C; Wippermann, Burkhard W; Blokhuis, Taco J; Patka, Peter; Bakker, Fred C; Haarman, Henk J Th M

    2003-05-01

    Hydroxyapatite is a synthetic bone graft, which is used for the treatment of bone defects and nonunions. However, it is a rather inert material with no or little intrinsic osteoinductive activity. Recombinant human osteogenic protein-1 (rhOP-1) is a very potent biological agent, that enhances osteogenesis during bone repair. Bone marrow contains mesenchymal stem cells, which are capable of new bone formation. Biosynthetic bone grafts were created by the addition of rhOP-1 or bone marrow to granular porous hydroxyapatite. The performance of these grafts was tested in a sheep model and compared to the results of autograft, which is clinically the standard treatment of bone defects and nonunions. A 3 cm segmental bone defect was made in the tibia and fixed with an interlocking intramedullary nail. There were five treatment groups: no implant (n=6), autograft (n=8), hydroxyapatite alone (n=8), hydroxyapatite loaded with rhOP-1 (n=8), and hydroxyapatite loaded with autologous bone marrow (n=8). At 12 weeks, healing of the defect was evaluated with radiographs, a torsional test to failure, and histological examination of longitudinal sections through the defect. Torsional strength and stiffness of the healing tibiae were about two to three times higher for autograft and hydroxyapatite plus rhOP-1 or bone marrow compared to hydroxyapatite alone and empty defects. The mean values of both combination groups were comparable to those of autograft. There were more unions in defects with hydroxyapatite plus rhOP-1 than in defects with hydroxyapatite alone. Although the differences were not significant, histological examination revealed that there was more often bony bridging of the defect in both combination groups and the autograft group than in the group with hydroxyapatite alone. Healing of bone defects, treated with porous hydroxyapatite, can be enhanced by the addition of rhOP-1 or autologous bone marrow. The results of these composite biosynthetic grafts are equivalent to

  16. Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Westphal, Ricardo João; Bueno, Ronaldo Rocha Loures; Galvão, Paulo Bezerra de Araújo; Zanis Neto, José; Souza, Juliano Mendes; Guérios, Ênio Eduardo; Senegaglia, Alexandra Cristina; Brofman, Paulo Roberto; Pasquini, Ricardo; da Cunha, Claudio Leinig Pereira

    2014-01-01

    Background Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation. PMID:25590932

  17. 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.

  18. Autologous Bone Marrow Derived Stem Cells for the Treatment of Multiple Sclerosis

    PubMed Central

    Chahine, Nassim Abi; Wehbe, Tarek; Rashed, Johny; Hilal, Ramzi; Elias, Nada

    2016-01-01

    Stem cell therapy, an evolving, progressive field of therapeutics has shown several successes in areas where classic treatments failed to prevent or stop disability. Starting in 2009, twenty two sequential patients with progressive Multiple Sclerosis (MS) courses were treated with Autologous Bone Marrow Mononuclear stem cells (BM-MNSCs). The cells were given both intravenously and intrathecally. Using the Expanded Disability Status Scale (EDSS) score for evaluation, our data indicates that the majority of the patients benefited on the average one point on the scale. This paper adds to the body of evidence suggesting the safety and efficacy of autologous BM-MNSCs in the treatment of MS and awaits validation through larger, randomized studies. PMID:27788571

  19. Allogeneic and Autologous Bone Marrow Transplantation in CHAMPUS 1989-1993 A Total Patient Treatment Episode Analysis.

    DTIC Science & Technology

    1993-10-22

    AUTOLOGOUS BONE MARROW TRANSPLANTATION IN CHAMPUS 1989-1993 A TOTAL PATIENT TREATMENT EPISODE ANALYSIS DR. SCOTT A. OPTENBERG, GM-15 Chief, Health Care...Analysis Division Directorate of Health Care Studies and Analyses DR. JAMES M. THOMPSON, LTC, USAF, MC (RET) Former Director, Bone Marrow...Department of the Air Force position unless so designated by other authorized documents. Authors’ current addresses: Directorate of Health Care

  20. Autologous bone marrow-derived cells for healing excisional dermal wounds of rabbits.

    PubMed

    Borena, B M; Pawde, A M; Amarpal; Aithal, H P; Kinjavdekar, P; Singh, R; Kumar, D

    2009-11-07

    The wound-healing potential of autologous bone marrow-derived nucleated cells was evaluated in full-thickness skin wounds in the thoracolumbar region of 20 clinically healthy rabbits. Three wounds of 2 x 2 cm, one on the left side and two right of the midline, were created on the dorsal lumbar region of each rabbit under xylazine-ketamine anaesthesia. The wounds of each animal were randomly assigned to one of three treatments: injection of autologous bone marrow-derived cells into wound margins (BI), topical application of bone marrow-derived cells over the wound surface (BT) or 5 per cent povidone iodine solution (PI) (control). Wounds were observed for 28 days for granulation tissue formation, wound contraction, histomorphological and histochemical evaluation, and time to complete healing. The mean (se) time to appearance of granulation tissue was significantly less in BI-treated wounds (3.22 [0.22] days) than the BT-treated (3.89 [0.40] days) and PI-treated (4.89 [0.47] days) groups. On days 14 and 21 after surgery, wound contraction was significantly (P<0.05) higher in BI-treated wounds (73.00 and 97.35 per cent) than in those treated with BT (58.75 and 84.87 per cent) and PI (54.84 and 84.60 per cent). Histomorphological findings showed an earlier disappearance of inflammatory reaction, better epithelialisation, significantly more neovascularisation, more fibroplasia and collagenation, and earlier histological maturation in BI- and BT-treated wounds than in control wounds.

  1. Safety and feasibility of transendocardial autologous bone marrow cell transplantation in patients with advanced heart disease.

    PubMed

    Fuchs, Shmuel; Kornowski, Ran; Weisz, Giora; Satler, Lowell F; Smits, Peter C; Okubagzi, Petros; Baffour, Richard; Aggarwal, Anita; Weissman, Neil J; Cerqueira, Manuel; Waksman, Ron; Serrruys, Parrick; Battler, Alexander; Moses, Jeffrey W; Leon, Martin B; Epstein, Stephen E

    2006-03-15

    The present report contains the final results of a Phase I study that evaluated the feasibility, safety, and potential efficacy of intramyocardial injection of autologous bone marrow (BM) in "no-option" patients with refractory angina and myocardial ischemia. Twenty-seven patients underwent electromechanic mapping-guided transendomyocardial injections (n = 12, 0.2 ml each) of unfractionated autologous BM cells directed to ischemic, noninfarcted myocardial territory. Patients were injected with 28 +/- 27 x 10(6)/ml nucleated cells containing 2.2 +/- 1.4% CD34+ cells. The autologous BM injection procedure was successful in all patients and was associated with no adverse events. At 3 months, the Canadian Cardiovascular Society angina score (3.2 +/- 0.5 vs 2.0 +/- 0.91, p = 0.001) and treadmill exercise duration (418 +/- 136 vs 489 +/- 142 seconds, p = 0.017) had improved significantly. The stress-induced ischemia score within the injected territories (118 segments) had also improved (2.2 +/- 0.8 vs 1.7 +/- 1.1, p < 0.001). At 1 year, the clinical improvement was sustained, although 5 patients had undergone revascularization procedures. The number of total injected nucleated cells (CD45+), progenitor cells (CD34+), and the magnitude of secreted vascular endothelial growth factor and macrophage chemoattractant protein-1 by cultured BM cells failed to predict the clinical response. In conclusion, the 3- and 12-month study results have indicated the safety of catheter-based transendocardial delivery of autologous BM cells in patients with advanced symptomatic ischemic heart disease and may suggest sustained potential efficacy. The cellular and humeral characteristics of autologous BM cells did not predict the clinical response, underscoring the advisability of additional mechanistic exploration.

  2. Disappearance of CD4 lymphocyte circadian cycles after autologous bone marrow transplantation.

    PubMed

    Martini, E; Gorin, N C; Gastal, C; Doinel, C; Roquin, H; Najman, A; Salmon, C

    1988-01-01

    Circadian variations are observed in CD4 lymphocyte count in healthy people. Samples taken of the basal value occurring around 08.00 hr and peak value at midnight made it possible to define the range of cyclic variations. Movement of lymphocytes seems important in accounting for the observed circadian variations. CD4 circadian cycle amplitudes were investigated in 12 patients with autologous bone marrow transplantation. Cycle abnormalities were observed in 7 patients. Two of them had a normal CD4 lymphocyte count. It was therefore possible for functional abnormalities in CD4 lymphocytes to be detected in patients with a normal CD4 count. Because of these results, we are of the opinion that the evaluation of CD4 lymphocyte cycle might be a more sensitive test than the absolute CD4 count itself.

  3. 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

  4. Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury.

    PubMed

    Kakabadze, Zurab; Kipshidze, Nickolas; Mardaleishvili, Konstantine; Chutkerashvili, Gocha; Chelishvili, Irakli; Harders, Albrecht; Loladze, George; Shatirishvili, Gocha; Kipshidze, Nodar; Chakhunashvili, David; Chutkerashvili, Konstantine

    2016-01-01

    Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50%) cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA) scale, 7 (78%) out of the 9 patients observed an improvement by one grade, while two cases (22%) saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury.

  5. Repair of orbital bone defects in canines using grafts of enriched autologous bone marrow stromal cells

    PubMed Central

    2014-01-01

    Backgroud Bone tissue engineering is a new approach for the repair of orbital defects. The aim of the present study was to explore the feasibility of tissue-engineered bone constructed using bone marrow stromal cells (BMSCs) that were rapidly isolated and concentrated from bone marrow (BM) by the red cell lysis method, then combined with β-tricalcium phosphate (β-TCP) to create grafts used to restore orbital bone defects in canines. Methods In the experimental group, grafts were constructed using BMSCs obtained by red cell lysis from 20 ml bone marrow, combined with β-TCP and BM via the custom-made stem cell-scaffold device, then used to repair 10 mm diameter medial orbital wall bony defects in canines. Results were compared with those in groups grafted with BM/β-TCP or β-TCP alone, or with defects left untreated as controls. The enrichment of BMSCs and nucleated cells (NCs) in the graft was calculated from the number in untreated bone marrow and in suspensions after red cell lysis. Spiral computed tomography (CT) scans were performed 1, 4, 12 and 24 weeks after implantation in all groups. Gross examination, micro-CT and histological measurements were performed 24 weeks after surgery. The results were analyzed to evaluate the efficacy of bone repair. Results The number of NCs and of colony-forming units within the scaffolds were increased 54.8 times and 53.4 times, respectively, compared with untreated bone marrow. In the BMSC-BM/β-TCP group, CT examination revealed that the scaffolds were gradually absorbed and the bony defects were restored. Micro-CT and histological examination confirmed that the implantations led to good repair of the defects, with 6 out 8 orbital defects completely restored in the experimental group, while by contrast, the grafts in the control groups did not fully repair the bony defects, a difference which was statistically significant (p < 0.05). Conclusions Tissue-engineered bone, constructed using BMSCs isolated by red cell

  6. Periodontal regeneration by autologous bone marrow mononuclear cells embedded in a novel thermo reversible gelation polymer.

    PubMed

    Sankaranarayanan, Seshadri; Jetty, Nadeem; Gadagi, Jayaprakash S; Preethy, Senthilkumar; Abraham, Samuel J K

    2013-01-01

    Regeneration of bony defects caused by periodontal disease continues to be a challenge for clinicians. Application of stem cells from different tissue sources and scaffolds for regeneration have been reported in animal models but clinical studies with long term follow-ups are limited. Herein we report the three years follow-up of the application of autologous bone marrow mononuclear cells (BMMNCs) embedded in a thermo-reversible gelation polymer (TGP) for periodontal regeneration. A 23-year female patient with advanced periodontitis (class IV gingival recession, probing pocket depth (PPD) of 5 mm and 6 mm in relation to mandibular lateral and central incisors respectively, and clinical attachment level (CAL) of 13 mm) correlated with radiographic evidence of severe horizontal bone loss extending up to the apex of mandibular incisors was selected for the treatment. After debridement, the defect was implanted with BMMNCs impregnated in TGP. Then the clinical parameters and radiographic evaluation were made at periodic intervals of 6, 12, 24 and 36 months. At six months, significant improvement with the clinical parameters (PPD had reduced to 2 mm, clinical attachment level had improved by 6 mm) was observed. At 36 months, the radiograph revealed bone regeneration with improvement in vertical and horizontal bone height. Transplantation of BMMNCs in a novel TGP is safe and results in a relatively significant and stable clinical outcome in horizontal alveolar bony defects.

  7. Application of Autologous Bone Marrow Derived Mesenchymal Stem Cells to an Ovine Model of Growth Plate Cartilage Injury

    PubMed Central

    McCarty, Rosa C; Xian, Cory J; Gronthos, Stan; Zannettino, Andrew C.W; Foster, Bruce K

    2010-01-01

    Injury to growth plate cartilage in children can lead to bone bridge formation and result in bone growth deformities, a significant clinical problem currently lacking biological treatment. Mesenchymal stem/stromal cells (MSC) offer a promising therapeutic option for regeneration of damaged cartilage, due to their self renewing and multi-lineage differentiation attributes. Although some small animal model studies highlight the therapeutic potential of MSC for growth plate repair, translational research in large animal models, which more closely resemble the human condition, are lacking. Our laboratory has recently characterised MSCs derived from ovine bone marrow, and demonstrated these cells form cartilage-like tissue when transplanted within the gelatin sponge, Gelfoam, in vivo. In the current study, autologous bone marrow MSC were seeded into Gelfoam scaffold containing TGF-β1, and transplanted into a surgically created defect of the proximal ovine tibial growth plate. Examination of implants at 5 week post-operatively revealed transplanted autologous MSC failed to form new cartilage structure at the defect site, but contributed to an increase in formation of a dense fibrous tissue. Importantly, the extent of osteogenesis was diminished, and bone bridge formation was not accelerated due to transplantation of MSCs or the gelatin scaffold. The current study represents the first work that has utilised this ovine large animal model to investigate whether autologous bone marrow derived MSC can be used to initiate regeneration at the injured growth plate. PMID:20721323

  8. Autologous Bone Marrow Mononuclear Cells Reduce Therapeutic Intensity for Severe Traumatic Brain Injury in Children

    PubMed Central

    Liao, George P.; Harting, Matthew T.; Hetz, Robert A.; Walker, Peter A.; DO, Shinil K. Shah; Corkins, Christopher J.; Hughes, Travis G.; Jimenez, Fernando; Kosmach, Steven C.; Day, Mary-Clare; Tsao, KuoJen; Lee, Dean A.; Worth, Laura L.; Baumgartner, James E.; Cox, Charles S.

    2014-01-01

    Objective The devastating effect of traumatic brain injury (TBI) is exacerbated by an acute secondary neuroinflammatory response, clinically manifest as elevated intracranial pressure (ICP) due to cerebral edema. The treatment effect of cell based therapies in the acute post-TBI period has not been clinically studied although preclinical data demonstrate that bone marrow derived mononuclear cell (BMMNC) infusion downregulates the inflammatory response. Our study evaluates whether pediatric TBI patients receiving intravenous, autologous BMMNCs within 48 hours of injury experienced a reduction in therapeutic intensity directed towards managing elevated ICP relative to matched controls. Design The study was a retrospective cohort design comparing pediatric patients in a Phase I clinical trial treated with intravenous autologous BMMNCs (n=10) to a control group of age and severity matched children (n=19). Setting The study setting was at Children's Memorial Hermann Hospital, an American College of Surgeons Level 1 Pediatric Trauma Center and teaching hospital for the University of Texas Health Science Center at Houston from 2000-2008. Patients Study patients were 5-14 years with post resuscitation Glasgow Coma Scale scores of 5-8. Interventions The treatment group received 6 million autologous BMMNC/kg body weight intravenously within 48 hours of injury. The control group was treated in an identical fashion, per standard of care, guided by our TBI management protocol, derived from American Association of Neurological Surgeons guidelines. Measurements The primary measure was the Pediatric Intensity Level of Therapy (PILOT) scale, used to quantify treatment of elevated ICP. Secondary measures included the Pediatric Logistic Organ Dysfunction (PELOD) score and days of ICP monitoring as a surrogate for length of neurointensive care. Main Results A repeated measure mixed model with marginal linear predictions identified a significant reduction in the PILOT score beginning

  9. Use of autologous bone marrow mononuclear cells and cultured bone marrow stromal cells in dogs with orthopaedic lesions.

    PubMed

    Crovace, A; Favia, A; Lacitignola, L; Di Comite, M S; Staffieri, F; Francioso, E

    2008-09-01

    The aim of the study is to evaluate the clinical application in veterinary orthopedics of bone marrow mononuclear cells (BMMNCs) and cultured bone marrow stromal cells (cBMSCs) for the treatment of some orthopaedic lesions in the dog. The authors carried out a clinical study on 14 dogs of different breed, age and size with the following lesions: 1 bone cyst of the glenoid rime; 2 nonunion of the tibia; 3 nonunion of the femur; 2 lengthening of the radius; 1 large bone defect of the distal radius;1 nonunion with carpus valgus; 4 Legg-Calvé-Perthés disease. In 9 cases the BMMCNs were used in combination with a three dimensional resorbable osteogenic scaffold the chemical composition and size of which facilitates the ingrowth of bone. In these cases the BMMNCs were suspended in an adequate amount of fibrin glue and then distribuited uniformly on a Tricalcium-Phosphate (TCP) scaffold onto which were also added some drops of thrombin. In 1 case of nonunion of the tibia and in 3 cases of Legg-Calvè-Perthés (LCP) disease the cultured BMSCs were used instead because of the small size of the dogs and of the little amount of aspirated bone marrow. X-ray examinations were performed immediately after the surgery. Clinical, ultrasounds and X-ray examinations were performed after 20 days and then every month. Until now the treated dogs have shown very good clinical and X-ray results. One of the objectives of the study was to use the BMMNCs in clinical application in orthopaedic lesions in the dog. The advantages of using the cells immediately after the bone marrow is collected, are that the surgery can be performed the same day, the cells do not need to be expanded in vitro, they preserve their osteogenic potential to form bone and promote the proper integration of the implant with the bone and lastly, the technique is easier and the costs are lower.

  10. Therapeutic Time Window and Dose Response of Autologous Bone Marrow Mononuclear Cells for Ischemic Stroke

    PubMed Central

    Yang, Bing; Strong, Roger; Sharma, Sushil; Brenneman, Miranda; Mallikarjunarao, Kasam; Xi, XiaoPei; Grotta, James C.; Aronowski, Jaroslaw; Savitz, Sean I.

    2012-01-01

    Although mononuclear cells (MNCs) from bone marrow are being investigated in phase I clinical trials in stroke patients, dose response, therapeutic time window and biodistribiton have not been well-characterized in animal stroke models. Long Evans rats underwent common carotid artery/middle cerebral artery occlusion (CCA/MCAo) and 24 hrs later were randomized to receive saline IV or a bone marrow aspiration followed by an IV infusion of autologous separated MNCs (1 million, 10 million or 30 million cells/kg). In another experiment, rats underwent CCAo/MCAo and were randomized at 24 hrs, 72 hrs or 7 days after stroke to receive a saline injection or 10 million/kg MNCs. All animals were evaluated on the cylinder and corner tests up to 28 days. MNCs were tracked using Q-dot nanocrystals to monitor biodistribution. Animals treated with MNCs at 10 million and 30 million cells/kg at 24 hrs after stroke had significant reductions in neurological deficits and lesion size compared to saline controls or animals treated with 1 million cells/kg. There was no difference in neurological deficits in the 10 and 30 million cell/kg groups at 28 days. Animals treated with MNCs at 72 hrs but not at 7 days showed a significant reduction in neurological deficits by 28 days. Labeled MNCs were found in the brain, spleen, lung, liver, and kidney at 1 hr and exponentially decreased over the ensuing week. In conclusion, we found a maximum reduction in neurological deficits at 10 and 30 million cells/kg and a therapeutic time window up to 72 hrs after stroke. PMID:21412816

  11. Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury.

    PubMed

    Syková, Eva; Homola, Ales; Mazanec, Radim; Lachmann, Hynek; Konrádová, Simona Langkramer; Kobylka, Petr; Pádr, Radek; Neuwirth, Jirí; Komrska, Vladimír; Vávra, Vladimir; Stulík, Jan; Bojar, Martin

    2006-01-01

    Stem cell transplants into spinal cord lesions may help to improve regeneration and spinal cord function. Clinical studies are necessary for transferring preclinical findings from animal experiments to humans. We investigated the transplantation of unmanipulated autologous bone marrow in patients with transversal spinal cord injury (SCI) with respect to safety, therapeutic time window, implantation strategy, method of administration, and functional improvement. We report data from 20 patients with complete SCI who received transplants 10 to 467 days postinjury. The follow-up examinations were done at 3, 6, and 12 months after implantation by two independent neurologists using standard neurological classification of SCI, including the ASIA protocol, the Frankel score, the recording of motor and somatosensory evoked potentials, and MRI evaluation of lesion size. We compared intra-arterial (via catheterization of a. vertebralis) versus intravenous administration of all mononuclear cells in groups of acute (10-30 days post-SCI, n=7) and chronic patients (2-17 months postinjury, n=13). Improvement in motor and/or sensory functions was observed within 3 months in 5 of 6 patients with intra-arterial application, in 5 of 7 acute, and in 1 of 13 chronic patients. Our case study shows that the implantation of autologous bone marrow cells appears to be safe, as there have been no complications following implantation to date (11 patients followed up for more than 2 years), but longer follow-ups are required to determine that implantation is definitively safe. Also, we cannot yet confirm that the observed beneficial effects were due to the cell therapy. However, the outcomes following transplantation in acute patients, and in one chronic patient who was in stable condition for several months prior to cell implantation, are promising. It is evident that transplantation within a therapeutic window of 3-4 weeks following injury will play an important role in any type of stem cell

  12. Repeated high-dose chemotherapy followed by purged autologous bone marrow transplantation as consolidation therapy in metastatic neuroblastoma.

    PubMed

    Hartmann, O; Benhamou, E; Beaujean, F; Kalifa, C; Lejars, O; Patte, C; Behard, C; Flamant, F; Thyss, A; Deville, A

    1987-08-01

    Among 62 children over 1 year of age at diagnosis, who were treated for stage IV neuroblastoma, 33 entered complete remission (CR) or good partial remission (GPR) after conventional therapy and received high-dose chemotherapy (HDC) with in vitro purged autologous bone marrow transplantation (ABMT) as consolidation therapy. The HDC was a combination of carmustine (BCNU), teniposide (VM-26), and melphalan. Thirty-three patients received one course of this regimen, and 18 received two courses. At present, 16 of the 33 grafted patients are alive in continuous CR, with a median follow-up of 28 months. Toxicity of this regimen was tolerable, principally marked by bone marrow depression and gastrointestinal (GI) tract complications. Four complication-related deaths were observed. Relapse post-ABMT occurred most often in the bone marrow. Under this treatment, actuarial disease-free survival is improved compared with that observed under conventional therapy.

  13. Bone Marrow Very Small Embryonic-Like Stem Cells: New Generation of Autologous Cell Therapy Soon Ready for Prime Time?

    PubMed

    Smadja, David M

    2017-01-18

    Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells described in human and mouse. In this issue of Stem Cell Reviews and Reports, Shaikh and colleagues show in a valuable work that mouse bone marrow collected after 5FU treatment contains VSELs able to undergo in vitro multi-lineage differentiation into cells from all three germ layers and also in germ and hematopoietic cells. These findings are robust since no confounding factor such as feeder cell fusion with VSELs can occur here. This paper allows one to better appreciate bone marrow-VSELs differentiation potential and opens new perspectives for autologous cell therapy. Furthermore, it might help explaining lots of contradictive data from the past 20 years, in particular related to ability of bone marrow cells to differentiate into cardiomyocytes.

  14. Autologous bone marrow-derived cell therapy combined with physical therapy induces functional improvement in chronic spinal cord injury patients.

    PubMed

    El-Kheir, Wael Abo; Gabr, Hala; Awad, Mohamed Reda; Ghannam, Osama; Barakat, Yousef; Farghali, Haithem A M A; El Maadawi, Zeinab M; Ewes, Ibrahim; Sabaawy, Hatem E

    2014-04-01

    Spinal cord injuries (SCI) cause sensory loss and motor paralysis. They are normally treated with physical therapy, but most patients fail to recover due to limited neural regeneration. Here we describe a strategy in which treatment with autologous adherent bone marrow cells is combined with physical therapy to improve motor and sensory functions in early stage chronic SCI patients. In a phase I/II controlled single-blind clinical trial (clinicaltrials.gov identifier: NCT00816803), 70 chronic cervical and thoracic SCI patients with injury durations of at least 12 months were treated with either intrathecal injection(s) of autologous adherent bone marrow cells combined with physical therapy or with physical therapy alone. Patients were evaluated with clinical and neurological examinations using the American Spinal Injury Association (ASIA) Impairment Scale (AIS), electrophysiological somatosensory-evoked potential, magnetic resonance imaging (MRI), and functional independence measurements. Chronic cervical and thoracic SCI patients (15 AIS A and 35 AIS B) treated with autologous adherent bone marrow cells combined with physical therapy showed functional improvements over patients in the control group (10 AIS A and 10 AIS B) treated with physical therapy alone, and there were no long-term cell therapy-related side effects. At 18 months posttreatment, 23 of the 50 cell therapy-treated cases (46%) showed sustained functional improvement. Compared to those patients with cervical injuries, a higher rate of functional improvement was achieved in thoracic SCI patients with shorter durations of injury and smaller cord lesions. Therefore, when combined with physical therapy, autologous adherent bone marrow cell therapy appears to be a safe and promising therapy for patients with chronic SCI of traumatic origin. Randomized controlled multicenter trials are warranted.

  15. Bone marrow aspiration

    MedlinePlus

    Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

  16. Autologous bone marrow injection in the management of simple bone cysts in children.

    PubMed

    Docquier, Pierre-Louis; Delloye, Christian

    2004-06-01

    The majority of simple bone cysts (SBC's) is not symptomatic and remains undiagnosed or is discovered fortuitously. A number of simple bone cysts are only diagnosed after a pathological fracture which occurs as a presenting symptom. Fractures are managed either conservatively or surgically, based on criteria such as the age of the child and the type and localisation of the fracture. The risk for fracture can be evaluated radiographically. In the absence of a fracture risk, plain radiographic follow-up is sufficient. In case of a high fracture risk, percutaneous aspiration and injection of bone marrow may be performed. The result of this treatment in 21 simple bone cysts with a high risk for fracture is reported. Slow regression of the cyst and progressive healing were obtained in 15 cases (71.4%) whereas no response was noted in 3 cases (14.3%) and recurrence in another 3 (14.3%), after a mean follow-up of 37.1 months. Guidelines are proposed for the follow-up and management of SBC.

  17. Chitosan nerve conduits seeded with autologous bone marrow mononuclear cells for 30 mm goat peroneal nerve defect

    PubMed Central

    Muheremu, Aikeremujiang; Chen, Lin; Wang, Xiyuan; Wei, Yujun; Gong, Kai; Ao, Qiang

    2017-01-01

    In the current research, to find if the combination of chitosan nerve conduits seeded with autologous bone marrow mononuclear cells (BM-MNCs) can be used to bridge 30 mm long peroneal nerve defects in goats, 15 animals were separated into BM-MNC group (n = 5), vehicle group (n = 5), and autologous nerve graft group (n = 5). 12 months after the surgery, animals were evaluated by behavioral observation, magnetic resonance imaging tests, histomorphological and electrophysiological analysis. Results revealed that animals in BM-MNC group and autologous nerve graft group achieved fine functional recovery; magnetic resonance imaging tests and histomorphometry analysis showed that the nerve defect was bridged by myelinated nerve axons in those animals. No significant difference was found between the two groups concerning myelinated axon density, axon diameter, myelin sheath thickness and peroneal nerve action potential. Animals in vehicle group failed to achieve significant functional recovery. The results indicated that chitosan nerve conduits seeded with autologous bone marrow mononuclear cells have strong potential in bridging long peripheral nerve defects and could be applied in future clinical trials. PMID:28287100

  18. Intrathecal Transplantation of Autologous Adherent Bone Marrow Cells Induces Functional Neurological Recovery in a Canine Model of Spinal Cord Injury.

    PubMed

    Gabr, Hala; El-Kheir, Wael Abo; Farghali, Haithem A M A; Ismail, Zeinab M K; Zickri, Maha B; El Maadawi, Zeinab M; Kishk, Nirmeen A; Sabaawy, Hatem E

    2015-01-01

    Spinal cord injury (SCI) results in demyelination of surviving axons, loss of oligodendrocytes, and impairment of motor and sensory functions. We have developed a clinical strategy of cell therapy for SCI through the use of autologous bone marrow cells for transplantation to augment remyelination and enhance neurological repair. In a preclinical large mammalian model of SCI, experimental dogs were subjected to a clipping contusion of the spinal cord. Two weeks after the injury, GFP-labeled autologous minimally manipulated adherent bone marrow cells (ABMCs) were transplanted intrathecally to investigate the safety and efficacy of autologous ABMC therapy. The effects of ABMC transplantation in dogs with SCI were determined using functional neurological scoring, and the integration of ABMCs into the injured cords was determined using histopathological and immunohistochemical investigations and electron microscopic analyses of sections from control and transplanted spinal cords. Our data demonstrate the presence of GFP-labeled cells in the injured spinal cord for up to 16 weeks after transplantation in the subacute SCI stage. GFP-labeled cells homed to the site of injury and were detected around white matter tracts and surviving axons. ABMC therapy in the canine SCI model enhanced remyelination and augmented neural regeneration, resulting in improved neurological functions. Therefore, autologous ABMC therapy appears to be a safe and promising therapy for spinal cord injuries.

  19. Chitosan nerve conduits seeded with autologous bone marrow mononuclear cells for 30 mm goat peroneal nerve defect.

    PubMed

    Muheremu, Aikeremujiang; Chen, Lin; Wang, Xiyuan; Wei, Yujun; Gong, Kai; Ao, Qiang

    2017-03-13

    In the current research, to find if the combination of chitosan nerve conduits seeded with autologous bone marrow mononuclear cells (BM-MNCs) can be used to bridge 30 mm long peroneal nerve defects in goats, 15 animals were separated into BM-MNC group (n = 5), vehicle group (n = 5), and autologous nerve graft group (n = 5). 12 months after the surgery, animals were evaluated by behavioral observation, magnetic resonance imaging tests, histomorphological and electrophysiological analysis. Results revealed that animals in BM-MNC group and autologous nerve graft group achieved fine functional recovery; magnetic resonance imaging tests and histomorphometry analysis showed that the nerve defect was bridged by myelinated nerve axons in those animals. No significant difference was found between the two groups concerning myelinated axon density, axon diameter, myelin sheath thickness and peroneal nerve action potential. Animals in vehicle group failed to achieve significant functional recovery. The results indicated that chitosan nerve conduits seeded with autologous bone marrow mononuclear cells have strong potential in bridging long peripheral nerve defects and could be applied in future clinical trials.

  20. 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.

  1. 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

  2. Intra-operative preparation of autologous bone marrow-derived CD34-enriched cellular products for cardiac therapy

    PubMed Central

    DONNENBERG, ALBERT D.; DONNENBERG, VERA S.; GRIFFIN, DEBORAH L.; MOORE, LINDA R.; TEKINTURHAN, FERDA; KORMOS, ROBERT L.

    2014-01-01

    Background and Aims With the advent of regenerative therapy, there is renewed interest in the use of bone marrow as a source of adult stem and progenitor cells, including cell subsets prepared by immunomagnetic selection. Cell selection must be rapid, efficient and performed according to current good manufacturing practices. In this report we present a methodology for intra-operative preparation of CD34+ selected autologous bone marrow for autologous use in patients receiving coronary artery bypass grafts or left ventricular assist devices. Methods and Results We developed a rapid erythrocyte depletion method using hydroxyethyl starch and low-speed centrifugation to prepare large-scale (mean 359 mL) bone marrow aspirates for separation on a Baxter Isolex 300i immunomagnetic cell separation device. CD34 recovery after erythrocyte depletion was 68.3 ± 20.2%, with an average depletion of 91.2 ± 2.8% and an average CD34 content of 0.58 ± 0.27%. After separation, CD34 purity was 64.1 ± 17.2%, with 44.3 ± 26.1% recovery and an average dose of 5.0 ± 2.7 × 10 6 CD34+ cells/product. In uncomplicated cases CD34-enriched cellular products could be accessioned, prepared, tested for release and administered within 6 h. Further analysis of CD34+ bone marrow cells revealed a significant proportion of CD45– CD34+ cells. Conclusions Intra-operative immunomagnetic separation of CD34-enriched bone marrow is feasible using rapid low-speed Hetastarch sedimentation for erythrocyte depletion. The resulting CD34-enriched product contains CD45– cells that may represent non-hematopoietic or very early hematopoietic stem cells that participate in tissue regeneration. PMID:21062114

  3. Myelodysplastic syndrome after autologous bone marrow transplantation: an additional late complication of curative cancer therapy.

    PubMed

    Miller, J S; Arthur, D C; Litz, C E; Neglia, J P; Miller, W J; Weisdorf, D J

    1994-06-15

    Myelodysplastic syndrome (MDS) is a complication of conventional antineoplastic therapy but has rarely been reported after autologous bone marrow transplantation (ABMT). We reviewed records of 206 patients who underwent ABMT for lymphoma at the University of Minnesota (Minneapolis, MN) between 1974 and 1993. Of 206 patients who underwent ABMT for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD), 9 patients developed an MDS or secondary acute leukemia between 5 and 60 months (median 34 months) post-BMT. Two patients had relapsed after transplant and received additional therapy before the diagnosis of MDS. They were censored from the statistical analysis, resulting in a cumulative incidence of 14.5% +/- 11.6% (95% confidence interval) at 5 years. Three patients (15.2% +/- 18.0%) had HD, and four (14.0% +/- 14.7%) had NHL. In vitro BM purging had no affect on the incidence of MDS, although patients receiving peripheral blood stem cells had a projected MDS incidence of 31% +/- 33% versus 10.5% +/- 12% if BM cells were used (p = .0035). The patients had received a median of 14 cycles (range, 6 to 40) of chemotherapy before autologous transplantation; Five of nine patients received radiation therapy before BMT conditioning, and all patients received radiation before the diagnosis of MDS. No BM cytogenetic abnormalities were evident pretransplant in three of three patients studied, and all nine had normal pretransplant BM morphology. All patients had morphologic BM findings typical of MDS, and six of six studied had clonal cytogenetic abnormalities. At the diagnosis of MDS, all nine patients were without clinical, radiographic, or autopsy evidence of recurrent lymphoma; Three of the nine patients have died from complications of cytopenias at 23, 36, and 45 months after transplant (3 to 10 months after the diagnosis of MDS), whereas 6 survive 8 to 63 months after transplantation (1 to 34 months post-MDS). These data emphasize the cumulative leukemogenic potential of

  4. Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation.

    PubMed

    Sebecić, B; Nikolić, V; Sikirić, P; Seiwerth, S; Sosa, T; Patrlj, L; Grabarević, Z; Rucman, R; Petek, M; Konjevoda, P; Jadrijević, S; Perović, D; Slaj, M

    1999-03-01

    Gastrectomy often results in increased likelihood of osteoporosis, metabolic aberration, and risk of fracture, and there is a need for a gastric peptide with osteogenic activity. A novel stomach pentadecapeptide, BPC-157, improves wound and fracture healing in rats in addition to having an angiogenic effect. Therefore, in the present study, using a segmental osteoperiosteal bone defect (0.8 cm, in the middle of the left radius) that remained incompletely healed in all control rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide BPC-157 was further studied (either percutaneously given locally [10 microg/kg body weight] into the bone defect, or applied intramuscularly [intermittently, at postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or continuously [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg body weight]). For comparison, rabbits percutaneously received locally autologous bone marrow (2 mL, postoperative day 7). As standard treatment, immediately after its formation, the bone defect was filled with an autologous cortical graft. Saline-treated (2 mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals were used as controls. Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects. For instance, upon radiographic assessment, the callus surface, microphotodensitometry, quantitative histomorphometry (10 microg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10 ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was shown to correspond to improvement after local application of bone marrow or autologous cortical graft. Moreover, a comparison of the number of animals with unhealed defects (all controls) or healed defects (complete bony continuity across the defect site) showed that besides pentadecapeptide intramuscular application for 14 days (i.e., local application of bone marrow or autologous cortical graft), also

  5. 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; Tasken, K; Tjønnfjord, G E; Schjesvold, F; Dalgaard, J; Tveita, A; Munthe, L A

    2017-02-24

    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 bone marrow 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.Leukemia accepted article preview online, 24 February 2017. doi:10.1038/leu.2017.69.

  6. Successful Repigmentation of Vitiligo after Allogeneic Bone Marrow Transplantation for Hodgkin's Lymphoma by Autologous Noncultured Melanocyte-keratinocyte Transplantation

    PubMed Central

    Tang, Huijuan; Wang, Cui; Fu, Lifang; Xu, Ai-e

    2015-01-01

    The treatment of vitiligo is derisory since the pathogenesis of vitiligo is not clear at present. Most conservative treatments are difficult to approach satisfactory therapy. So transplantation is the only way left when the disease becomes insensitive to those conservative treatments. Here we describe an 18-year-old patient who developed vitiligo, which was triggered by graft-versus-host disease after a allogeneic bone marrow transplantation for the treatment of Hodgkin's lymphoma from his sister. In the following treatment to vitiligo, the patient successfully performed the transplantation of autologous uncultured melanocyte on the premise of poor reaction to other conservative methods. We infer that transplantation can be a treatment of the vitiligo after allogeneic bone marrow transplantation. PMID:26538694

  7. Autologous bone marrow mononuclear cells enhance recovery after acute ischemic stroke in young and middle-aged rats

    PubMed Central

    Brenneman, Miranda; Sharma, Sushil; Harting, Matthew; Strong, Roger; Cox, Charles S; Aronowski, Jarek; Grotta, James C; Savitz, Sean I

    2010-01-01

    We investigated intra-arterially administered autologous bone marrow mononuclear cells (MNCs) in rats with acute ischemic stroke. Long Evans rats (2 to 3 months or 12 months old) underwent tandem reversible common carotid artery (CCA)/middle cerebral artery (MCA) occlusion (CCAo/MCAo) for 3 h and then 24 h later underwent tibial bone marrow harvest. Ten million or 4 million cells were re-injected by an intra-carotid infusion. Control animals underwent marrow needle insertion and then saline injection into the carotid artery. Animals were assessed on a battery of neurological tests. MNCs in the ischemic brain were tracked using Q-dot nanocrystal labeling. Infarct volume and cytokines in the ischemia-affected brain were analyzed. Cell-treated animals in the younger and older groups showed improvement from 7 to 30 days after stroke compared with vehicle-treated animals. MNCs significantly reduced infarct volume compared with saline. There was a significant reduction in tumor necrosis factor-α, interleukin-1α (IL-1α), IL-β, IL-6, and a significant increase in IL-10 in injured brains harvested from the cell-treated groups compared with saline controls. Labeled MNCs were found in the peri-infarcted area at 1 h and exponentially decreased over the ensuing week after injection. Autologous bone marrow MNCs can be safely harvested from rodents after stroke, migrate to the peri-infarct area, enhance recovery, and modulate the post-ischemic inflammatory response. PMID:19773802

  8. Busulfan, cyclophosphamide, and melphalan conditioning for autologous bone marrow transplantation in hematologic malignancy.

    PubMed

    Phillips, G L; Shepherd, J D; Barnett, M J; Lansdorp, P M; Klingemann, H G; Spinelli, J J; Nevill, T J; Chan, K W; Reece, D E

    1991-10-01

    Sixteen patients with poor-prognosis acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL) underwent conditioning with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BUCY-2) plus melphalan (90 or 135 mg/m2) and autologous bone marrow transplantation (AuBMT) in a phase I study. At the melphalan dose of 90 mg/m2, grade greater than or equal to 3 regimen-related toxicity (RRT) was observed in five patients (31%; 95% confidence interval [CI], 11% to 59%), with hepatic (venoocclusive disease [VOD]) and urinary (hemorrhagic cystitis) RRT being the most frequent complications. Further escalation of the melphalan dose to 135 mg/m2 was deemed excessively toxic, as three of five patients had grade greater than or equal to 3 RRT. Following this experience, 21 patients with multiple myeloma (MM) and chronic myelogenous leukemia (CML) were treated with BUCY-2 plus melphalan 90 mg/m2 and AuBMT in separate studies. Three of these patients--all with extensively pretreated MM--had grade greater than or equal to 3 RRT (14%; 95% CI, 3% to 36%); no others had grade greater than or equal to 3 RRT. Therefore, a total of eight of the 37 patients (22%; 95% CI, 10% to 38%) who received BUCY-2 plus melphalan 90 mg/m2 conditioning developed grade greater than or equal to 3 RRT; three of these patients (8%; 95% CI, 3% to 25%) died of RRT. Although limited by the relatively small number of patients, our analysis of the patients receiving this regimen showed that the presence of parameters denoting the lymphoid diagnostic group (ie, ALL, NHL, and MM), more extensive pretreatment, and/or more advanced disease status were associated with a higher incidence of grade greater than or equal to 3 RRT. Response data on the AML, ALL, and NHL patients who received BUCY-2 plus melphalan 90 mg/m2 were analyzed: three patients (all with AML in first or second remission) are leukemia-free at 3.0, 2.8, and 1.4 years after AuBMT. The actuarial 2-year

  9. Special considerations for the patient undergoing allogeneic or autologous bone marrow transplantation.

    PubMed

    Hiemenz, J W; Greene, J N

    1993-10-01

    Improvements in the diagnosis, treatment, and prevention of infectious complications of bone marrow transplantation over the past two decades have markedly reduced the morbidity and mortality of this procedure. We are now able to begin early empiric antibiotic coverage with less toxic, but equally effective, antibacterial agents. Once believed to be uniformly fatal, complications such as CMV pneumonia are now considered treatable in at least half the cases with a combination of intravenous immunoglobulin and ganciclovir. Although probably the most controversial, prophylactic therapy has improved the outcome of patients undergoing bone marrow transplantation. The appropriate setting, agents to use, dose, and dose intervals will require further study in coming years. In the introduction to this article, we attempted to outline what is known about the immunobiology of bone marrow transplantation. A clear understanding of this process helps us recognize and anticipate the infectious complications encountered in this population of patients. It may also allow clinicians to focus more on immune augmentation as a means of prevention, as has been attempted with the newly available cytokines and the use of intravenous immunoglobulin infusions. Despite improvements in diagnosis, treatment, and prevention, infectious complications remain the leading cause of morbidity and mortality in the patient undergoing bone marrow transplantation. Future studies are required in this area to build on the successes of the last two decades.

  10. Repeated Autologous Bone Marrow-Derived Mesenchymal Stem Cell Injections Improve Radiation-Induced Proctitis in Pigs

    PubMed Central

    Busson, Elodie; Holler, Valerie; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Lhomme, Bruno; Prat, Marie; Devauchelle, Patrick; Sabourin, Jean-Christophe; Simon, Jean-Marc; Bonneau, Michel; Lataillade, Jean-Jacques; Benderitter, Marc

    2013-01-01

    The management of proctitis in patients who have undergone very-high-dose conformal radiotherapy is extremely challenging. The fibrosis-necrosis, fistulae, and hemorrhage induced by pelvic overirradiation have an impact on morbidity. Augmenting tissue repair by the use of mesenchymal stem cells (MSCs) may be an important advance in treating radiation-induced toxicity. Using a preclinical pig model, we investigated the effect of autologous bone marrow-derived MSCs on high-dose radiation-induced proctitis. Irradiated pigs received repeated intravenous administrations of autologous bone marrow-derived MSCs. Immunostaining and real-time polymerase chain reaction analysis were used to assess the MSCs' effect on inflammation, extracellular matrix remodeling, and angiogenesis, in radiation-induced anorectal and colon damages. In humans, as in pigs, rectal overexposure induces mucosal damage (crypt depletion, macrophage infiltration, and fibrosis). In a pig model, repeated administrations of MSCs controlled systemic inflammation, reduced in situ both expression of inflammatory cytokines and macrophage recruitment, and augmented interleukin-10 expression in rectal mucosa. MSC injections limited radiation-induced fibrosis by reducing collagen deposition and expression of col1a2/col3a1 and transforming growth factor-β/connective tissue growth factor, and by modifying the matrix metalloproteinase/TIMP balance. In a pig model of proctitis, repeated injections of MSCs effectively reduced inflammation and fibrosis. This treatment represents a promising therapy for radiation-induced severe rectal damage. PMID:24068742

  11. Transdifferentiation of autologous bone marrow cells on a collagen-poly(ε-caprolactone) scaffold for tissue engineering in complete lack of native urothelium

    PubMed Central

    Zhao, J.; Zeiai, S.; Ekblad, Å.; Nordenskjöld, A.; Hilborn, J.; Götherström, C.; Fossum, M.

    2014-01-01

    Urological reconstructive surgery is sometimes hampered by a lack of tissue. In some cases, autologous urothelial cells (UCs) are not available for cell expansion and ordinary tissue engineering. In these cases, we wanted to explore whether autologous mesenchymal stem cells (MSCs) from bone marrow could be used to create urological transplants. MSCs from human bone marrow were cultured in vitro with medium conditioned by normal human UCs or by indirect co-culturing in culture well inserts. Changes in gene expression, protein expression and cell morphology were studied after two weeks using western blot, RT-PCR and immune staining. Cells cultured in standard epithelial growth medium served as controls. Bone marrow MSCs changed their phenotype with respect to growth characteristics and cell morphology, as well as gene and protein expression, to a UC lineage in both culture methods, but not in controls. Urothelial differentiation was also accomplished in human bone marrow MSCs seeded on a three-dimensional poly(ε-caprolactone) (PCL)–collagen construct. Human MSCs could easily be harvested by bone marrow aspiration and expanded and differentiated into urothelium. Differentiation could take place on a three-dimensional hybrid PCL-reinforced collagen-based scaffold for creation of a tissue-engineered autologous transplant for urological reconstructive surgery. PMID:24789561

  12. Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells into the Testes of Infertile Male Rats and New Germ Cell Formation

    PubMed Central

    Ghasemzadeh-Hasankolaei, Mohammad; Batavani, Roozali; Eslaminejad, Mohamadreza Baghaban; Sayahpour, Foroughazam

    2016-01-01

    Background Mesenchymal stem cells (MSCs), have been suggested as a potential choice for treatment of male infertility. Yet, the effects of MSCs on regeneration of germinal epithelium of seminiferous tubules and recovery of spermatogenesis have remained controversial. In this research, we have evaluated and compared the fate of autologous bone marrow (BM)-MSCs during three different periods of time- 4, 6 and 8 weeks after transplantation into the testes of busulfan-induced infertile male rats. Methods Rats BM samples were collected from tibia bone under anesthesia. The samples were directly cultured in culture medium. Isolated, characterized and purified BM-MSCs were labeled with PKH26, and transplanted into the testes of infertile rats. After 4, 6 and 8 weeks, the testes were removed and underwent histological evaluations. Results Immunohistochemical analysis showed that transplanted BM-MSCs survived in all three groups. Some of the cells homed at the germinal epithelium and expressed spermatogonia markers (Dazl and Stella). The number of homed spermatogonia-like cells in 4-week testes, was more than the 6-week testes. The 8-week testes had the least numbers of homed cells (p<0.05). Immunostaining for vimentin showed that BM-MSCs did not differentiate into the sertoli cells in the testes. Conclusions From our results, it could be concluded that, autologous BM-MSCs could survive in the testis, migrate onto the seminiferous tubules basement membrane and differentiate into spermatogonia. Although, no more differentiation was observed in the produced spermatogonia, generation of such endogenous GCs would be a really promising achievement for treatment of male infertility using autologous stem cells. PMID:27430978

  13. Combined autologous bone marrow mononuclear cell and gene therapy as the last resort for patients with critical limb ischemia

    PubMed Central

    Skóra, Jan; Pupka, Artur; Janczak, Dariusz; Barć, Piotr; Dawiskiba, Tomasz; Korta, Krzysztof; Baczyńska, Dagmara; Garcarek, Jerzy

    2014-01-01

    Introduction Our study was designed to investigate the safety and efficacy of combined autologous bone marrow mononuclear cell (MNC) and gene therapy in comparison to conventional drug therapy in patients with critical limb ischemia (CLI). Material and methods Thirty-two patients with CLI persisting for 12–48 months (average time 27.5 months) were randomized into 2 groups, each group consisting of 16 patients. In the first group, administration of autologous bone marrow MNC and vascular endothelial growth factor (VEGF) plasmid was performed. The patients from the second group were treated pharmacologically with pentoxifylline. Ankle-brachial index (ABI) was measured and angiography was performed before and finally 3 months after treatment. The pain was evaluated using the Visual Analog Scale (VAS) before and after 3 months. Results Ankle-brachial index improved significantly from 0.29 ±0.21 to 0.52 ±0.23 (p < 0.001) in 12 patients (75.0%) 3 months after the experimental therapy in group 1. In this group angiography showed the development of collateral vessels. Ischemic ulcers healed completely in 11 patients (68.75%). In group 2 the ABI did not improve in any patient; moreover the complete healing of skin ulcers was not found in any of the patients of this group. Amputation was performed in 4 (25.0%) patients in group 1, and in 8 patients (50%) from group 2. Conclusions These data after 3-month follow-up indicate that intramuscular injection of MNC combined with gene therapy in patients with chronic CLI is safe, and a more feasible and effective method of treatment than the conventional therapy. However, both therapies are limited by the degree of microcirculation damage. PMID:25995748

  14. High-dose therapy and autologous bone marrow transplantation in first complete or partial remission for poor prognosis Hodgkin's disease.

    PubMed

    Fleury, J; Legros, M; Colombat, P; Cure, H; Travade, P; Tortochaux, J; Dionet, C; Chollet, P; Linassier, C; Lamagnere, J P; Blaise, D; Viens, P; Maraninchi, D; Plagne, R

    1996-01-01

    We report the experience of three French centres which evaluated high-dose therapy (HDT) as consolidation therapy for poor prognosis Hodgkin's disease (HD). From March 1986 to April 1990, 23 consecutive patients with poor prognosis stage IV HD underwent HDT followed by autologous bone marrow transplantation (ABMT) after achieving either complete remission (CR1) or good partial response (GPR1) (reduction mass> 75%). The median age was 31 years (range 18 to 55 years), 14 were male. All patients except one initially had at least 2 poor prognosis factors such as: systemic symptoms (n = 19), bulky tumor (n = 16), more than one extranodal site (n = 9), bone marrow involvement (n = 5), lymphocyte count < or = 1.10(9)/1 (n = 8) and biological stage B (n = 21). All patients had previously been treated with alternating MOPP/ABVD. Ten patients were in GPR1 and 13 in CR1 before transplant. The conditioning regimens were: CBV (n = 17), BEAM (n = 5), BEAC (n = 1) followed by bone marrow rescue. Radiotherapy was introduced just before the conditioning regimen for 6 patients or after ABMT for 5 patients. Nine of 10 patients in GPR1 achieved CR after ABMT but one died early of treatment-related toxicity. Five of 22 patients who were in CR posttransplant, relapsed (3, 4, 4, 18, 36 months). Seventeen patients remain alive in continuous CR with a median follow-up of 60 months (range: 30-100 months). The overall survival (OS) and disease-free survival (DFS) projected at 5 years are 92% and 77% respectively. Consolidation by HDT and ABMT proved to be well tolerated. An international trial is currently underway to attempt to demonstrate a clear benefit on survival for this subset of poor prognosis HD patients.

  15. Effect of Autologous Bone Marrow Stromal Cell Seeding and Bone Morphogenetic Protein-2 Delivery on Ectopic Bone Formation in a Microsphere/Poly(Propylene Fumarate) Composite

    PubMed Central

    Kempen, Diederik H.R.; Kruyt, Moyo C.; Lu, Lichun; Wilson, Clayton E.; Florschutz, Anthony V.; Yaszemski, Michael J.; Dhert, Wouter J.A.

    2009-01-01

    A biodegradable microsphere/scaffold composite based on the synthetic polymer poly(propylene fumarate) (PPF) holds promise as a scaffold for cell growth and sustained delivery vehicle for growth factors for bone regeneration. The objective of the current work was to investigate the in vitro release and in vivo bone forming capacity of this microsphere/scaffold composite containing bone morphogenetic protein-2 (BMP-2) in combination with autologous bone marrow stromal cells (BMSCs) in a goat ectopic implantation model. Three composites consisting of 0, 0.08, or 8 μg BMP-2 per mg of poly(lactic-co-glycolic acid) microspheres, embedded in a porous PPF scaffold, were combined with either plasma (no cells) or culture-expanded BMSCs. PPF scaffolds impregnated with a BMP-2 solution and combined with BMSCs as well as empty PPF scaffolds were also tested. The eight different composites were implanted subcutaneously in the dorsal thoracolumbar area of goats. Incorporation of BMP-2–loaded microspheres in the PPF scaffold resulted in a more sustained in vitro release with a lower burst phase, as compared to BMP-2–impregnated scaffolds. Histological analysis after 9 weeks of implantation showed bone formation in the pores of 11/16 composites containing 8 μg/mg BMP-2–loaded microspheres with no significant difference between composites with or without BMSCs (6/8 and 5/8, respectively). Bone formation was also observed in 1/8 of the BMP-2–impregnated scaffolds. No bone formation was observed in the other conditions. Overall, this study shows the feasibility of bone induction by BMP-2 release from microspheres/scaffold composites. PMID:18925831

  16. Cotransplantation of autologous bone marrow stromal cells and chondrocytes as a novel therapy for reconstruction of condylar cartilage.

    PubMed

    Dai, Jiewen; Wang, Xudong; Shen, Guofang

    2011-07-01

    Condylar cartilage is absolutely necessary for the normal function of temporomandibular joint (TMJ). Unfortunately, condylar cartilage defect or missing is also one of the common clinical problems. Repair or reconstruction of cartilage is always a hot topic. Cell based cartilage regeneration is suggested as novel therapies in cartilage tissue engineering, and autologous chondrocytes were initially regarded as the ideal cell source. However, there are some disadvantages such as its limited augmentation capability for culture in vitro and may differentiate to other types of cells. On the other hand, bone marrow stromal cells (BMSCs) have gained special interest in tissue engineering. Because they can be obtained easily, cause relatively minor trauma and show the potential of long-run ex vivo expansion capacity. What most important is their capacity of multi-directional differentiation. They can differentiate into a variety of other types of cells when there are supplement exogenous factors or genes, but their clinical use is limited by safety concerns such as toxicity, insertional teratogenic, uncontrollable gene expression. Fortunately, the chondrocytes microenvironment has been demonstrated that could induce BMSCs to structure cartilage when culture in vitro or reimplanted in nude mice subcutaneously area. So in this article, we hypothesize that cotransplantation of autologous BMSCs and chondrocytes, which coculture with extracellular scaffolds, is a novel therapy for reconstruction of TMJ condylar cartilage. In our strategy, advantages of two types of cells are utilized and shortcomings are avoided, which strongly improve the feasibility and clinical safety, finally bring great hope to the patients with TMJ disease.

  17. Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet-Rich Plasma Accelerate Distraction Osteogenesis in A Canine Model

    PubMed Central

    Dehghan, Mohammad Mehdi; Baghaban Eslaminejad, Mohamadreza; Motallebizadeh, Nader; Ashrafi Halan, Javad; Tagiyar, Leila; Soroori, Sarang; Nikmahzar, Agbibi; Pedram, Mirsepehr; Shahverdi, Abdolhossein; Kazemi Mehrjerdi, Hossein; Izadi, Sadra

    2015-01-01

    Objective Distraction osteogenesis (DO) is a surgical procedure used to generate large volumes of new bone for limb lengthening. Materials and Methods In this animal experimental study, a 30% lengthening of the left tibia (mean distraction distance: 60.8 mm) was performed in ten adult male dogs by callus distraction after osteotomy and application of an Ilizarov fixator. Distraction was started on postoperative day seven with a distraction rate of 0.5 mm twice per day and carried out at a rate of 1.5 mm per day until the end of the study. Autologous bone marrow mesenchymal stem cells (BM-MSCs) and platelet-rich plasma (PRP) as the treatment group (n=5) or PRP alone (control group, n=5) were injected into the distracted callus at the middle and end of the distraction period. At the end of the consolidation period, the dogs were sacrificed after which computerized tomography (CT) and histomorphometric evaluations were performed. Results Radiographic evaluationsrevealed that the amount and quality of callus formations were significantly higher in the treatment group (P<0.05). As measured by CT scan, the healing parametersin dogs of the treatment group were significantly greater (P<0.05). New bone formation in the treatment group was significantly higher (P<0.05). Conclusion The present study showed that the transplantation of BM-MSCs positively affects early bony consolidation in DO. The use of MSCs might allow a shortened period of consolidation and therefore permit earlier device removal. PMID:26199903

  18. Preliminary Study of Autologous Bone Marrow Nucleated Cells Transplantation in Children With Spinal Cord Injury

    PubMed Central

    Jarocha, Danuta; Milczarek, Olga; Kawecki, Zdzislaw; Wendrychowicz, Anna; Kwiatkowski, Stanislaw

    2014-01-01

    The objective of this study was to assess the safety and efficacy of transplanting bone marrow nucleated cells (BMNCs) to treat children with complete interruption of spinal cord (SC) continuity. The present study was conducted from 2005 to 2011. The inclusion criteria were a magnetic resonance imaging-confirmed complete interruption of SC continuity and no improvement in neurological status within 6 months after standard therapy. Bone marrow was isolated from the iliac ala and submitted to BMNC isolation. Subsequently, the cell suspension was administered into the SC cavity and intravenously. In total, 18 of 19 intraspinal and intravenous BMNC transplantation procedures performed caused no adverse events. One case was connected with transient bradycardia. The experimental therapy showed no late complications in the 1- to 6-year follow-up evaluation period. Neurological improvement was observed in two patients who received multiple implantations. One patient demonstrated improved superficial sensation from Th3 to Th12/L1 and a restored bladder-filling sensation. In the other case, superficial sensation was improved from C2 to C5, and the respiratory drive, the swallowing reflex, and tongue movements were restored. Spasticity and quality of life were improved in three of five patients. In addition, skin pressure ulcers healed and did not recur. Our preliminary results demonstrate the safety and feasibility of BMNC transplantation in children with complete SC injury. The results indicate that a certain degree of neurological and quality-of-life improvement can be attained by children with chronic complete SC injury who receive multiple BMNC implantations. PMID:24493853

  19. Autologous bone marrow stromal cells are promising candidates for cell therapy approaches to treat bone degeneration in sickle cell disease.

    PubMed

    Lebouvier, Angélique; Poignard, Alexandre; Coquelin-Salsac, Laura; Léotot, Julie; Homma, Yasuhiro; Jullien, Nicolas; Bierling, Philippe; Galactéros, Frédéric; Hernigou, Philippe; Chevallier, Nathalie; Rouard, Hélène

    2015-11-01

    Osteonecrosis of the femoral head is a frequent complication in adult patients with sickle cell disease (SCD). To delay hip arthroplasty, core decompression combined with concentrated total bone marrow (BM) treatment is currently performed in the early stages of the osteonecrosis. Cell therapy efficacy depends on the quantity of implanted BM stromal cells. For this reason, expanded bone marrow stromal cells (BMSCs, also known as bone marrow derived mesenchymal stem cells) can be used to improve osteonecrosis treatment in SCD patients. In this study, we quantitatively and qualitatively evaluated the function of BMSCs isolated from a large number of SCD patients with osteonecrosis (SCD-ON) compared with control groups (patients with osteonecrosis not related to SCD (ON) and normal donors (N)). BM total nuclear cells and colony-forming efficiency values (CFE) were significantly higher in SCD-ON patients than in age and sex-matched controls. The BMSCs from SCD-ON patients were similar to BMSCs from the control groups in terms of their phenotypic and functional properties. SCD-ON patients have a higher frequency of BMSCs that retain their bone regeneration potential. Our findings suggest that BMSCs isolated from SCD-ON patients can be used clinically in cell therapy approaches. This work provides important preclinical data that is necessary for the clinical application of expanded BMSCs in advanced therapies and medical products.

  20. Intravenous Autologous Bone Marrow Mononuclear Cell Transplantation for Stroke: Phase1/2a Clinical Trial in a Homogeneous Group of Stroke Patients

    PubMed Central

    Sakai, Chiaki; Soma, Toshihiro; Kasahara, Yukiko; Stern, David M.; Kajimoto, Katsufumi; Ihara, Masafumi; Daimon, Takashi; Yamahara, Kenichi; Doi, Kaori; Kohara, Nobuo; Nishimura, Hiroyuki; Matsuyama, Tomohiro; Naritomi, Hiroaki; Sakai, Nobuyuki; Nagatsuka, Kazuyuki

    2015-01-01

    The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke. Major inclusion criteria included patients with cerebral embolism, age 20–75 years, National Institute of Health Stroke Scale (NIHSS) score displaying improvement of ≤5 points during the first 7 days after stroke, and NIHSS score of ≥10 on day 7 after stroke. Bone marrow aspiration (25 or 50 mL; N = 6 patients in each case) was performed 7–10 days poststroke, and bone marrow mononuclear cells were administrated intravenously. Mean total transplanted cell numbers were 2.5 × 108 and 3.4 × 108 cells in the lower and higher dose groups, respectively. No apparent adverse effects of administering bone marrow cells were observed. Compared with the lower dose, patients receiving the higher dose of bone marrow cells displayed a trend toward improved neurologic outcomes. Compared with 1 month after treatment, patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment. In comparison with historical controls, patients receiving cell therapy had significantly better neurologic outcomes. Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible. Positive results and trends favoring neurologic recovery and improvement in cerebral blood flow and metabolism by cell therapy underscore the relevance of larger scale randomized controlled trials using this approach. PMID:26176265

  1. Long-term clinical results of autologous bone marrow CD 133+ cell transplantation in patients with ST-elevation myocardial infarction

    NASA Astrophysics Data System (ADS)

    Kirgizova, M. A.; Suslova, T. E.; Markov, V. A.; Karpov, R. S.; Ryabov, V. V.

    2015-11-01

    The aim of the study was investigate the long-term results of autologous bone marrow CD 133+ cell transplantation in patients with primary ST-Elevation Myocardial Infarction (STEMI). Methods and results: From 2006 to 2007, 26 patients with primary STEMI were included in an open randomized study. Patients were randomized to two groups: 1st - included patients underwent PCI and transplantation of autologous bone marrow CD 133+ cell (n = 10); 2nd - patients with only PCI (n = 16). Follow-up study was performed 7.70±0.42 years after STEMI and consisted in physical examination, 6-min walking test, Echo exam. Total and cardiovascular mortality in group 1 was lower (20% (n = 2) vs. 44% (n = 7), p = 0.1 and 22% (n = 2) vs. 25% (n = 4), (p=0.53), respectively). Analysis of cardiac volumetric parameters shows significant differences between groups: EDV of 100.7 ± 50.2 mL vs. 144.40±42.7 mL, ESV of 56.3 ± 37.8 mL vs. 89.7 ± 38.7 mL in 1st and 2nd groups, respectively. Data of the study showed positive effects of autologous bone marrow CD 133+ cell transplantation on the long-term survival of patients and structural status of the heart.

  2. Use of autologous mesenchymal stem cells derived from bone marrow for the treatment of naturally injured spinal cord in dogs.

    PubMed

    Penha, Euler Moraes; Meira, Cássio Santana; Guimarães, Elisalva Teixeira; Mendonça, Marcus Vinícius Pinheiro; Gravely, Faye Alice; Pinheiro, Cláudia Maria Bahia; Pinheiro, Taiana Maria Bahia; Barrouin-Melo, Stella Maria; Ribeiro-Dos-Santos, Ricardo; Soares, Milena Botelho Pereira

    2014-01-01

    The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were cultured in vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury.

  3. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury.

    PubMed

    Dai, Guanghui; Liu, Xuebin; Zhang, Zan; Yang, Zhijun; Dai, Yiwu; Xu, Ruxiang

    2013-10-02

    Neuronal injuries have been a challenging problem for treatment, especially in the case of complete and chronic cervical spinal cord injury (SCI). Recently, particular attention is paid to the potential of stem cell in treating SCI, but there are only few clinical studies and insufficient data. This study explored the efficacy of autologous bone marrow mesenchymal stem cells (BMMSCs) transplantation in the treatment of SCI. Forty patients with complete and chronic cervical SCI were selected and randomly assigned to one of the two experimental groups, treatment group and control group. The treatment group received BMMSCs transplantation to the area surrounding injury, while the control group was not treated with any cell transplantation. Both the transplant recipients and the control group were followed up to 6 months, postoperatively. Preoperative and postoperative neurological functions were evaluated with AIS grading, ASIA score, residual urine volume and neurophysiological examination. Results showed that in the treatment group 10 patients had a significant clinical improvement in terms of motor, light touch, pin prick sensory and residual urine volume, while nine patients showed changes in AIS grade. Neurophysiological examination was consistent with clinical observations. No sign of tumor was evident until 6 months postoperatively. In the control group, no improvement was observed in any of the neurological functions specified above. BMMSCs transplantation improves neurological function in patients with complete and chronic cervical SCI, providing valuable information on applications of BMMSCs for the treatment of SCI.

  4. Effect of autologous bone marrow-derived cells associated with guided bone regeneration or not in the treatment of peri-implant defects.

    PubMed

    Ribeiro, F V; Suaid, F F; Ruiz, K G S; Rodrigues, T L; Carvalho, M D; Nociti, F H; Sallum, E A; Casati, M Z

    2012-01-01

    This study investigated the effect of bone marrow-derived cells associated with guided bone regeneration in the treatment of dehiscence bone defects around dental implants. Iliac-derived bone marrow cells were harvested from dogs and phenotypically characterized with regard to their osteogenic properties. After teeth extraction, three implant sites were drilled, dehiscences created and implants placed. Dehiscences were randomly assigned to: bone marrow-derived cells, bone marrow-derived cells+guided bone regeneration, and control (no treatment). After 3 months, implants with adjacent tissues were processed histologically, bone-to-implant contact, bone fill within the threads, new bone area in a zone lateral to the implant, new bone height, and new bone weight at the bottom of the defect were determined. Phenotypic characterization demonstrated that bone marrow-derived cells presented osteogenic potential. Statistically higher bone fill within the threads was observed in both bone marrow-derived cells+guided bone regeneration bone marrow-derived cell groups compared with the control group (P<0.05), with no difference between the groups treated with cells (P>0.05). For the other parameters (new bone area, bone-to-implant contact, new bone height and new bone weight), only the bone marrow-derived cells+guided bone regeneration group presented higher values compared with the non-treated control (P<0.05). Bone marrow-derived cells provided promising results for peri-implantar bone regeneration, although the combined approach seems to be relevant, especially to bone formation out of the implant threads.

  5. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture

    PubMed Central

    Muir, Peter; Hans, Eric C.; Racette, Molly; Volstad, Nicola; Sample, Susannah J.; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L.; Bloom, Debra D.; Bleedorn, Jason A.; Hao, Zhengling; Amene, Ermias; Suresh, M.; Hematti, Peiman

    2016-01-01

    Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response

  6. Clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation: a meta-analysis of seven case-control studies.

    PubMed

    Yuan, Heng-Feng; Zhang, Jing; Guo, Chang-An; Yan, Zuo-Qin

    2016-02-01

    The purpose of this study was to evaluate the clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation. We searched the PubMed, Embase and Web of Science databases and included all case-control trials that reported on the clinical outcomes of osteonecrosis progression, incidence of total hip arthroplasty and improvement in Harris hip scores. Overall, seven case-control trials were included. Compared with the controls, patients treated with the bone marrow stem cells implantation treatment showed improved clinical outcomes with delayed osteonecrosis progression (odds ratio = 0.17, 95% CI: 0.09 - 0.32; p <0.001), a lower total hip arthroplasty incidence (odds ratio = 0.30, 95% CI: 0.12 - 0.72; p <0.01) and increased Harris hip scores (mean difference = 4.76, 95% CI: 1.24 - 8.28; p<0.01). The heterogeneity, publication bias, and sensitivity analyses showed no statistical difference significant differences between studies. Thus, our study suggests that autologous bone marrow stem cells implantation has a good therapeutic effect on osteonecrosis of the femoral, resulting in beneficial clinical outcomes. However, trials with larger sample sizes are needed to confirm these findings.

  7. Catheter–Based Transendocardial Delivery of Autologous Bone-Marrow-Derived Mononuclear Cells in Patients Listed for Heart Transplantation

    PubMed Central

    Silva, Guilherme V.; Perin, Emerson C.; Dohmann, Hans F.R.; Borojevic, Radovan; Silva, Suzana A.; Sousa, Andre L.S.; Assad, Joao A.R.; Vaughn, William K.; Mesquita, Claudio T.; Belém, Luciano; Carvalho, Antonio C.; Dohmann, Hans J.F.; do Amaral, Ellen Barroso; Coutinho, Joaquim; Branco, Rodrigo; Oliveira, Edie; Willerson, James T.

    2004-01-01

    Growing evidence suggests that transplantation of autologous bone-marrow mononuclear cells (ABMMNCs) can improve the perfusion and contractile function of ischemic myocardium. This procedure could potentially benefit transplant candidates awaiting a donor heart. To study the safety and feasibility of ABMMNC injection, we performed a prospective, nonrandomized, open-label study in 5 heart transplant candidates with severe ischemic heart failure. Each patient underwent baseline single-photon emission computed tomography, a ramp treadmill protocol, 2-dimensional echocardiography, 24-hour Holter monitoring, and signal-averaged electrocardiography, which were repeated at 2 and 6 months. Transendocardial delivery of ABMMNCs was done with the aid of electromechanical mapping to identify viable myocardium. Each patient received 15 ABMMNC injections of 0.2 cc each. There were no deaths, significant arrhythmias, or other major complications. The ABMMNC injection reduced the amount of ischemic myocardium (not statistically significant). More important, exercise test results improved significantly. Myocardial volume oxygen consumption increased from 10.6 ± 3 mL/kg/min (baseline) to 16.3 ± 7 mL/kg/min (2 months) and 23 ± 7 mL/kg/min (6 months) (P = 0.0091). In 4 of the 5 cases, this was such an improvement that the patients were no longer eligible for cardiac transplantation. In addition, metabolic equivalents improved from 3.03 ± 0.66 (baseline) to 4.65 ± 1.99 (2 months) and 6.5 ± 2.0 (6 months) (P = 0.0092). In conclusion, ABMMNC injections were performed safely and resulted in improved exercise capacity. This technique may hold promise as an alternative to medical management in patients with severe ischemic heart failure who are ineligible for conventional revascularization. PMID:15562839

  8. Bone marrow transplant - discharge

    MedlinePlus

    Transplant - bone marrow - discharge; Stem cell transplant - discharge; Hematopoietic stem cell transplant - discharge; Reduced intensity; Non-myeloablative transplant - discharge; Mini transplant - discharge; Allogenic bone marrow transplant - ...

  9. The role of children's bone marrow mesenchymal stromal cells in the ex vivo expansion of autologous and allogeneic hematopoietic stem cells.

    PubMed

    Pelagiadis, Iordanis; Stiakaki, Eftichia; Choulaki, Christianna; Kalmanti, Maria; Dimitriou, Helen

    2015-10-01

    The recognition of the role of Mesenchymal Stromal Cells (MSC) in hematopoiesis, as part of the bone marrow microenvironment, renewed the interest for cord blood (CB) ex vivo expansion as a source of HSC for transplantation. MSC from children are recognized to have different biological properties compared to the ones from adults. The current study focuses on the evaluation of the effects of children's bone marrow MSC on the ex vivo expansion capacity of both allogeneic cord blood and autologous bone marrow (BM) CD34(+) hematopoietic stem cells (HSCs) when used as a cell feeder layer with or without recombinant cytokines. Our results showed that children's bone marrow-derived MSC expand more primitive populations in co culture with CD34 and that the expansion is further enhanced when the culture is supplemented with growth factors. No additive effect was seen either with the early- or late-acting growth factors' cocktails used. Biological features of CB hematopoietic progenitors seem to make them more suitable than their BM counterparts for ex vivo expansion. Clinical implementation will be facilitated by methodological standardization and guidelines' establishment.

  10. Autologous human-derived bone marrow cells exposed to a novel TGF-beta1 fusion protein for the treatment of critically sized tibial defect.

    PubMed

    Becerra, José; Guerado, Enrique; Claros, Silvia; Alonso, Mônica; Bertrand, María L; González, Carlos; Andrades, José A

    2006-03-01

    We report the first clinical case of transplantation of autologous bone marrow-derived cells in vitro exposed to a novel recombinant human transforming growth factor (rhTGF)-beta1 fusion protein bearing a collagen-binding domain (rhTGF-beta(1)-F2), dexamethasone (DEX) and beta-glycerophosphate (beta-GP). When such culture-expanded cells were loaded into porous ceramic scaffolds and transplanted into the bone defect of a 69-year-old man, they differentiated into bone tissue. Marrow cells were obtained from the iliac crest and cultured in collagen gels impregnated with rhTGF-beta1-F2. Cells were selected under serum-restricted conditions in rhTGF-beta(1)-F2-containing medium for 10 days, expanded in 20% serum for 22 days and osteoinduced for 3 additional days in DEX/beta-GP-supplemented medium. We found that the cell number harvested from rhTGF-beta(1)-F2-treated cultures was significantly higher (2.3- to 3-fold) than that from untreated cultures. rhTGF-beta(1)-F2 treatment also significantly increased alkaline phosphatase activity (2.2- to 5-fold) and osteocalcin synthesis, while calcium was only detected in rhTGF-beta(1)-F2-treated cells. Eight weeks after transplantation, most of the scaffold pores were filled with bone and marrow tissue. When we tested the same human cells treated in vitro in a rat model using diffusion chambers, there was subsequent development of cartilage and bone following the subcutaneous transplantation of rhTGF-beta(1)-F2-treated cells. This supports the suggestion that such cells were marrow-derived cells, with chondrogenic and osteogenic potential, whereas the untreated cells were not under the same conditions. The ability for differentiation into cartilage and bone tissues, combined with an extensive proliferation capacity, makes such a marrow-derived stem cell population valuable to induce bone regeneration at skeletal defect sites.

  11. Rationale and Design for the Intramyocardial Injection of Autologous Bone Marrow Mononuclear Cells for Patients with Chronic Ischemic Heart Disease and Left Ventricular Dysfunction Trial (FOCUS)

    PubMed Central

    Willerson, James T.; Perin, Emerson C.; Ellis, Stephen G.; Pepine, Carl J.; Henry, Timothy D.; Zhao, David X.M.; Lai, Dejian; Penn, Marc S.; Byrne, Barry J.; Silva, G; Gee, Adrian; Traverse, Jay H.; Hatzopoulos, Antonis K.; Forder, John R.; Martin, Daniel; Kronenberg, Marvin; Taylor, Doris A.; Cogle, Christopher R.; Baraniuk, Sarah; Westbrook, Lynette; Sayre, Shelly L.; Vojvodic, Rachel W.; Gordon, David J.; Skarlatos, Sonia I.; Moyé, Lemuel A.; Simari, Robert D.

    2010-01-01

    Background The increasing worldwide prevalence of coronary artery disease (CAD) continues to challenge the medical community. Management options include medical and revascularization therapy. Despite advances in these methods, CAD is a leading cause of recurrent ischemia and heart failure, posing significant morbidity and mortality risks along with increasing health costs in a large patient population worldwide. Trial Design The Cardiovascular Cell Therapy Research Network (CCTRN) was established by the National Institutes of Health to investigate the role of cell therapy in the treatment of chronic cardiovascular disease. FOCUS is a CCTRN-designed randomized Phase II, placebo-controlled clinical trial that will assess the effect of autologous bone marrow mononuclear cells delivered transendocardially to patients with left ventricular (LV) dysfunction and symptomatic heart failure or angina. All patients need to have limiting ischemia by reversible ischemia on SPECT assessment. Results After thoughtful consideration of both statistical and clinical principles, we will recruit 87 patients (58 cell treated and 29 placebo) to receive either bone marrow–derived stem cells or placebo. Myocardial perfusion, LV contractile performance, and maximal oxygen consumption are the primary outcome measures. Conclusions The designed clinical trial will provide a sound assessment of the effect of autologous bone marrow mononuclear cells in improving blood flow and contractile function of the heart. The target population is patients with CAD and LV dysfunction with limiting angina or symptomatic heat failure. Patient safety is a central concern of the CCTRN, and patients will be followed for at least 5 years. PMID:20691824

  12. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds.

    PubMed

    Falanga, Vincent; Iwamoto, Satori; Chartier, Molly; Yufit, Tatyana; Butmarc, Janet; Kouttab, Nicholas; Shrayer, David; Carson, Polly

    2007-06-01

    The nonhematopoietic component of bone marrow includes multipotent mesenchymal stem cells (MSC) capable of differentiating into fat, bone, muscle, cartilage, and endothelium. In this report, we describe the cell culture and characterization, delivery system, and successful use of topically applied autologous MSC to accelerate the healing of human and experimental murine wounds. A single bone marrow aspirate of 35-50 mL was obtained from patients with acute wounds (n = 5) from skin cancer surgery and from patients with chronic, long-standing, nonhealing lower extremity wounds (n = 8). Cells were grown in vitro under conditions favoring the propagation of MSC, and flow cytometry and immunostaining showed a profile (CD29+, CD44+, CD105+, CD166+, CD34-, CD45-) highly consistent with published reports of human MSC. Functional induction studies confirmed that the MSC could differentiate into bone, cartilage, and adipose tissue. The cultured autologous MSC were applied up to four times to the wounds using a fibrin polymer spray system with a double-barreled syringe. Both fibrinogen (containing the MSC) and thrombin were diluted to optimally deliver a polymerized gel that immediately adhered to the wound, without run-off, and yet allowing the MSC to remain viable and migrate from the gel. Sequential adjacent sections from biopsy specimens of the wound bed after MSC application showed elongated spindle cells, similar to their in vitro counterparts, which immunostained for MSC markers. Generation of new elastic fibers was evident by both special stains and antibodies to human elastin. The application of cultured cells was safe, without treatment-related adverse events. A strong direct correlation was found between the number of cells applied (greater than 1 x 10(6) cells per cm2 of wound area) and the subsequent decrease in chronic wound size (p = 0.0058). Topical application of autologous MSC also stimulated closure of full-thickness wounds in diabetic mice (db

  13. Evaluation of transport conditions for autologous bone marrow-derived mesenchymal stromal cells for therapeutic application in horses.

    PubMed

    Espina, Miguel; Jülke, Henriette; Brehm, Walter; Ribitsch, Iris; Winter, Karsten; Delling, Uta

    2016-01-01

    Background. Mesenchymal stromal cells (MSCs) are increasingly used for clinical applications in equine patients. For MSC isolation and expansion, a laboratory step is mandatory, after which the cells are sent back to the attending veterinarian. Preserving the biological properties of MSCs during this transport is paramount. The goal of the study was to compare transport-related parameters (transport container, media, temperature, time, cell concentration) that potentially influence characteristics of culture expanded equine MSCs. Methods. The study was arranged in three parts comparing (I) five different transport containers (cryotube, two types of plastic syringes, glass syringe, CellSeal), (II) seven different transport media, four temperatures (4 °C vs. room temperature; -20 °C vs. -80 °C), four time frames (24 h vs. 48 h; 48 h vs. 72 h), and (III) three MSC concentrations (5 × 10(6), 10 × 10(6), 20 × 10(6) MSC/ml). Cell viability (Trypan Blue exclusion; percent and total number viable cell), proliferation and trilineage differentiation capacity were assessed for each test condition. Further, the recovered volume of the suspension was determined in part I. Each condition was evaluated using samples of six horses (n = 6) and differentiation protocols were performed in duplicates. Results. In part I of the study, no significant differences in any of the parameters were found when comparing transport containers at room temperature. The glass syringe was selected for all subsequent evaluations (highest recoverable volume of cell suspension and cell viability). In part II, media, temperatures, or time frames had also no significant influence on cell viability, likely due to the large number of comparisons and small sample size. Highest cell viability was observed using autologous bone marrow supernatant as transport medium, and "transport" at 4 °C for 24 h (70.6% vs. control group 75.3%); this was not significant. Contrary, viability was unacceptably low (<40

  14. Evaluation of transport conditions for autologous bone marrow-derived mesenchymal stromal cells for therapeutic application in horses

    PubMed Central

    Espina, Miguel; Jülke, Henriette; Brehm, Walter; Ribitsch, Iris; Winter, Karsten

    2016-01-01

    Background. Mesenchymal stromal cells (MSCs) are increasingly used for clinical applications in equine patients. For MSC isolation and expansion, a laboratory step is mandatory, after which the cells are sent back to the attending veterinarian. Preserving the biological properties of MSCs during this transport is paramount. The goal of the study was to compare transport-related parameters (transport container, media, temperature, time, cell concentration) that potentially influence characteristics of culture expanded equine MSCs. Methods. The study was arranged in three parts comparing (I) five different transport containers (cryotube, two types of plastic syringes, glass syringe, CellSeal), (II) seven different transport media, four temperatures (4 °C vs. room temperature; −20 °C vs. −80 °C), four time frames (24 h vs. 48 h; 48 h vs. 72 h), and (III) three MSC concentrations (5 × 106, 10 × 106, 20 × 106 MSC/ml). Cell viability (Trypan Blue exclusion; percent and total number viable cell), proliferation and trilineage differentiation capacity were assessed for each test condition. Further, the recovered volume of the suspension was determined in part I. Each condition was evaluated using samples of six horses (n = 6) and differentiation protocols were performed in duplicates. Results. In part I of the study, no significant differences in any of the parameters were found when comparing transport containers at room temperature. The glass syringe was selected for all subsequent evaluations (highest recoverable volume of cell suspension and cell viability). In part II, media, temperatures, or time frames had also no significant influence on cell viability, likely due to the large number of comparisons and small sample size. Highest cell viability was observed using autologous bone marrow supernatant as transport medium, and “transport” at 4 °C for 24 h (70.6% vs. control group 75.3%); this was not significant. Contrary, viability was unacceptably low

  15. Autologous bone marrow transplantation in poor-risk high-grade non-Hodgkin's lymphoma in first complete remission. Newcastle and Northern Lymphoma Group.

    PubMed Central

    Jackson, G. H.; Lennard, A. L.; Taylor, P. R.; Carey, P.; Angus, B.; Lucraft, H.; Evans, R. G.; Proctor, S. J.

    1994-01-01

    We report the safety and efficacy of autologous bone marrow transplantation (ABMT) in 30 patients with high-grade non-Hodgkin's lymphoma (NHL) in first complete remission (CR1) following remission induction chemotherapy. Two patients relapsed prior to ABMT. All patients were conditioned with high-dose melphalan. In Addition, ten received fractionated total body irradiation, one hemi-body irradiation and four high-dose etoposide. Unmanipulated non-cryopreserved autologous marrow was reinfused within 56 h of harvesting. Engraftment occurred in all patients with a median of 11 days of neutropenia (< 0.5 x 10(9) l-1), a median requirement for platelet transfusion of 3 days and packed red cell transfusion of 2 units, with a median hospital stay of 18 days post transplant. There was no procedure-related mortality and only minor morbidity was observed. Two patients relapsed at 1 and 2 months post transplantation, and one patient died of carcinoma of the lung 33 months after transplantation. The remaining 25 patients remain alive, well and in CR1 with a median follow-up of 44 months. The event-free survival at 3 years for all patients considered for ABMT was 83%. We conclude that ABMT for high-grade NHL in CR1 with non-cryopreserved marrow results in rapid haematological recovery without growth factor support. It is safe and is associated with high survival when used as consolidation of CR in high-risk patients. PMID:7521662

  16. Intraventricular Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells via Ommaya Reservoir in Persistent Vegetative State Patients after Haemorrhagic Stroke: Report of Two Cases & Review of the Literature

    PubMed Central

    Fauzi, Asra Al; Suroto, Nur Setiawan; Bajamal, Abdul Hafid; Machfoed, Moh. Hasan

    2016-01-01

    Background: One of the most devastating diseases, stroke, is a leading cause of death and disability worldwide with severe emotional and economic consequences. The purpose of this article is mainly to report the effect of intraventricular transplantation via an Ommaya reservoir using autologous bone marrow mesenchymal stem cells (BM-MSCs) in haemorrhagic stroke patients. Case Presentations: Two patients, aged 51 and 52, bearing sequels of haemorrhagic stroke were managed by intraventricular transplantation of BM-MSCs obtained from their own bone marrow. Before the procedure, both patients were bedridden, tracheostomised, on nasogastric (NG) tube feeding and in hemiparesis. The cells were transplanted intraventricularly (20 x 106 cells/2.5 ml) using an Ommaya reservoir, and then repeated transplantations were done after 1 and 2 months consecutively. The safety and efficacy of the procedures were evaluated 3, 6 and 12 months after treatment. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the patients’ neurological status before and after treatment. No adverse events derived from the procedures or transplants were observed in the one-year follow-up period, and the neurological status of both patients improved after treatment. Conclusions: Our report demonstrates that the intraventricular transplantation of BM-MSCs via an Ommaya reservoir is safe and it improves the neurological status of post-haemorrhagic stroke patients. The repeated transplantation procedure is easier and safer to perform via a subcutaneously implanted Ommaya reservoir. Key Words: Haemorrhagic stroke, bone marrow mesenchymal stem cells (BM-MSCs), intraventricular transplantation PMID:28096634

  17. Dose-intensified bendamustine followed by autologous peripheral blood stem cell support in relapsed and refractory multiple myeloma with impaired bone marrow function.

    PubMed

    Breitkreutz, Iris; Becker, Natalia; Benner, Axel; Kosely, Florentina; Heining, Christoph; Hillengass, Jens; Egerer, Gerlinde; Ho, Anthony D; Goldschmidt, Hartmut; Raab, Marc S

    2016-12-01

    Therapeutic options in heavily pretreated relapsed/refractory multiple myeloma patients are often very limited because of impaired bone marrow function. Bendamustine is effective in multiple myeloma and has a favourable toxicity profile. We hypothesized that dose-intensified bendamustine (180 mg/m(2) , day 1 and 2) followed by autologous blood stem cell support (ASCS) would improve bone marrow function with low post-transplant toxicity in patients with severely impaired haematopoiesis. We analyzed 28 consecutive myeloma patients, with a median of three prior lines of therapy (range 2-7), who had relapsed from the last treatment with very limited bone marrow function and were therefore ineligible for conventional chemotherapy, novel agents or trial enrolment. Dose-intensified bendamustine with ASCS improved haematopoiesis as reflected by increased platelet counts (median 40/nl vs 94/nl, p = 0.0004) and white blood cell counts (3.0/nl vs 4.8/nl, p = 0.02) at day +100. The median time until engraftment of platelets (>50/nl) was 11 days (0-24 days) and of white cell counts (>1.0/nl) 0 days (0-24 days). At least, a minimal response was achieved in 36% of patients. The disease stabilization rate was 50% while the median progression-free survival rate was limited to 2.14 months. Most importantly, patients were once again eligible for alternative treatments including enrolment into clinical trials. We conclude that dose-intensified bendamustine followed by ASCS is safe and feasible for multiple myeloma patients with very limited bone marrow reserve. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Autologous Bone Marrow Mononuclear Cell Therapy is Safe and Promotes Amputation Free Survival in Patients with Critical Limb Ischemia

    PubMed Central

    Murphy, Michael P.; Lawson, Jeffrey H.; Rapp, Brian M.; Dalsing, Michael C.; Klein, Janet; Wilson, Michael G.; Hutchins, Gary D.; March, Keith L.

    2011-01-01

    Objective The purpose of this phase I open label non-randomized trial was to assess the safety and efficacy of autologous bone marrow mononuclear cell (ABMNC) therapy in promoting amputation free survival (AFS) in patients with critical limb ischemia (CLI). Methods Between September 2005 and March 2009 twenty-nine patients (30 limbs), with a median age of 66 (range 23–84) (14 male,15 female) with CLI were enrolled . Twentyone limbs presented with rest pain (RP), six with RP and ulceration, and three with ulcer only. All patients were not candidates for surgical bypass due to absence of a patent artery below the knee and/or endovascular approaches to improving perfusion was not possible as determined by an independent vascular surgeon. Patients were treated with an average dose of 1.7 ± 0.7 × 109 ABMNC injected intramuscularly in the index limb distal to the anterior tibial tuberosity. The primary safety endpoint was accumulation of serious adverse events and the primary efficacy endpoint was AFS at one year. Secondary endpoints at 12 weeks post-treatment were changes in first toe pressure (FTP), toe-brachial index (TBI), ankle-brachial index (ABI), and transcutaneous oxygen measurements (TcPO2). Perfusion of the index limb was measured with PET-CT with intra-arterial infusion of H2O15. Rest pain (RP), using a 10-cm visual analog scale, quality of life using the VascuQuol questionnaire, and ulcer healing were assessed at each follow-up interval. Subpopulations of endothelial progenitor cells were quantified prior to ABMNC administration using immunocytochemistry and fluorescent activated cell sorting. Results There were two serious adverse events however there no procedure related deaths. Amputation-free survival at one-year was 86.3%. There was a significant increase in FTP (10.2+ 6.2 mmHg, P=.02) and TBI (0.10± 0.05, P=.02) and a trend in improvement in ABI (0.08±0.04, P=.73). Perfusion Index by PET-CT H2O15 increased by 19.3 ± 3.1 and RP decreased

  19. Comparison of osteogenic potentials of BMP4 transduced stem cells from autologous bone marrow and fat tissue in a rabbit model of calvarial defects.

    PubMed

    Lin, Lin; Shen, Qi; Wei, Xuelei; Hou, Yu; Xue, Tao; Fu, Xin; Duan, Xiaoning; Yu, Changlong

    2009-07-01

    We compared bone marrow stem cells (BMSCs) and adipose-derived stem cells (ADSCs) of adult rabbits under identical conditions in terms of their culture characteristics, proliferation capacity, osteogenic differentiation potentials induced by adenovirus-containing bone morphogenetic protein 4 (Ad-BMP4) in vitro, and capacity to repair calvarial defects in the rabbit model by autologous transplantation ex vivo. According to the results of growth curve, cell cycle, and telomerase activity analysis, ADSCs possess a higher proliferation potential. Both of the Ad-BMP4 transduced MSCs expressed BMP4 mRNA and protein and underwent osteogenic differentiation. Up-regulated mRNA expression of all osteogenic genes was observed in differentiated BMSCs and ADSCs, but with different patterns confirmed by real-time RT-PCR. Deposition of calcified extracellular matrix was significantly greater in differentiated ADSCs compared with differentiated BMSCs. X-ray and histological examination indicated significant bone regeneration in the calvarial defects transplanted with Ad-BMP4 transduced autologous MSCs compared to the control groups. There was no significant difference in new bone formation in Ad-BMP4 transduced MSCs based on quantitative digital analysis of histological sections. The use of ADSCs often resulted in the growth of fat tissue structures in the control groups, and the fat tissue structures were not seen with BMSC cells. Our data demonstrate that BMP4 can be potently osteoinductive in vivo, resulting in bone repair. ADSCs may be an attractive alternative to BMSCs for bone tissue engineering under appropriate stimuli. But the easy adipogenic differentiation needs to be considered when choosing adipose tissue for specific clinical application.

  20. Feasibility and Efficacy of Autologous Bone Marrow Aspirate Transplantation Combined with Human Parathyroid Hormone 1-34 Administration to Treat Osteonecrosis in a Rabbit Model

    PubMed Central

    Sugaya, Hisashi; Aoto, Katsuya; Uemura, Kenta; Tanaka, Kenta; Akaogi, Hiroshi; Yamazaki, Masashi; Mishima, Hajime

    2017-01-01

    No studies have examined the transplantation of a bone marrow aspirate (BMA) containing mesenchymal stem cells (MSCs) combined with human parathyroid hormone 1-34 (hPTH1-34) administration. Therefore, we evaluated the feasibility and efficacy of autologous BMA transplantation combined with hPHT1-34 administration in a bone necrosis model. The metatarsal bones of rabbits were necrotized using liquid nitrogen, and the rabbits received a BMA transplantation or saline injection followed by hPTH1-34 (30 μg/kg) or saline administration three times per week (n = 3-4 per group). The rabbits were euthanized at 12 weeks after the initiation of treatment. No systemic adverse effects or local neoplastic lesions were observed. Importantly, the rabbits in the BMA transplantation plus hPTH1-34 group showed the highest bone volumes and histological scores of new bone. These data confirmed the feasibility of BMA transplantation combined with hPTH1-34, at least during the experimental period. The observed efficacy may be explained by a synergistic effect from the stimulation of MSC differentiation to osteoblasts with hPTH1-34-mediated suppression of apoptosis in osteoblasts. These results indicate the promising potential for BMA transplantation combined with hPTH1-34 administration in bone necrosis treatment. Longer term experiments are needed to confirm the safety of this therapeutic strategy. PMID:28386485

  1. Bone marrow culture

    MedlinePlus

    ... There may be some bleeding at the puncture site. More serious risks, such as serious bleeding or infection, are very rare. Alternative Names Culture - bone marrow Images Bone marrow aspiration References ...

  2. Chronic lymphocytic leukemia B cells inhibit spontaneous Ig production by autologous bone marrow cells: role of CD95-CD95L interaction.

    PubMed

    Sampalo, A; Navas, G; Medina, F; Segundo, C; Cámara, C; Brieva, J A

    2000-11-01

    A variable degree of humoral immunodeficiency is a common feature in patients with B-cell chronic lymphocytic leukemia (B-CLL). The aim of this study was to explore the possibility that B-CLL cells play a direct role in this phenomenon. To this end, patients' bone marrow (BM) immunoglobulin (Ig)-secreting cells were cocultured with autologous purified B-CLL cells. The results show that tumoral cells inhibited the spontaneous IgG secretion by BM plasma cells, and this effect increased after PMA-induction of B-CLL cells. This inhibitory process was proportional to the number of B-CLL cells added and depended on cellular contact. Adhesion molecules did not appear to be involved in the cellular interaction, because the inclusion of blocking antibody to a variety of these proteins did not reverse the inhibitory phenomenon. However, the addition of monoclonal antibody that blocked the function of either CD95 or CD95L clearly reversed B-CLL cell inhibition on autologous BM plasma cells. These latter cells were shown to express CD95, and B-CLL cells contained detectable quantities of CD95L at the level of messenger RNA and protein. Annexin V-binding experiments revealed increased apoptosis of BM Ig-secreting cells when cocultured with autologous B-CLL cells. Finally, this inhibitory phenomenon might be operative in vivo because (a) there was a good correlation between the intensity of the inhibitory effect in vitro and the serum IgG level exhibited by every patient and (b) B-CLL cells also inhibited in vivo antigen-induced IgG-tetanus toxoid-secreting cells obtained from normal immunized subjects. Collectively, these data suggest that B-CLL cells inhibit autologous CD95-bearing Ig-secreting cells by the interaction with CD95L present on B-CLL cells and, hence, contribute to the state of humoral immunodeficiency that occurs in these patients.

  3. [Voluminous bone graft harvesting of the femoral marrow cavity for autologous transplantation. An indication for the"Reamer-Irrigator-Aspirator-" (RIA-)technique].

    PubMed

    Kobbe, P; Tarkin, I S; Frink, M; Pape, H C

    2008-06-01

    Due to their excellent osteoinductive, osteogenetic, and osteoconductive properties, autologous bone grafts possess biomechanical advantages over synthetic bone substitutes. Furthermore, unlike cadaveric allografts and xenografts, they carry no risk of immunogenic response or transmission of infectious diseases. However, the limited availability of autologous bone grafts requires the use of the above-mentioned bone substitutes for management of large bone defects. The"Reamer-Irrigator-Aspirator-" (RIA-)technique may present an alternative method for harvesting a larger volume of autologous bone graft as compared with conventional harvesting procedures. We report on intramedullary reaming by the RIA technique to obtain autologous bone graft for a nonunion of the proximal femur. The contralateral femur was reamed and the bone graft was applied to the nonunion. The patient showed clinical and radiological healing of the nonunion without donor site complications.

  4. Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor.

    PubMed

    Park, Hyung Chun; Shim, Yoo Shik; Ha, Yoon; Yoon, Seung Hwan; Park, So Ra; Choi, Byung Hyune; Park, Hyun Seon

    2005-01-01

    Transplantation of bone marrow cells into the injured spinal cord has been found to improve neurologic functions in experimental animal studies. However, it is unclear whether bone marrow cells can similarly improve the neurologic functions of complete spinal cord injury (SCI) in human patients. To address this issue, we evaluated the therapeutic effects of autologous bone marrow cell transplantation (BMT) in conjunction with the administration of granulocyte macrophage-colony stimulating factor (GM-CSF) in six complete SCI patients. BMT in the injury site (1.1 x 10(6) cells/microL in a total of 1.8 mL) and subcutaneous GM-CSF administration were performed on five patients. One patient was treated with GM-CSF only. The follow-up periods were from 6 to 18 months, depending on the patients. Sensory improvements were noted immediately after the operations. Sensory recovery in the sacral segment was noted mainly 3 weeks to 7 months postoperatively. Significant motor improvements were noted 3 to 7 months postoperatively. Four patients showed neurologic improvements in their American Spiral Injury Association Impairment Scale (AIS) grades (from A to C). One patient improved to AIS grade B from A and the last patient remained in AIS grade A. No immediate worsening of neurologic symptoms was found. Side effects of GMCSF treatment such as a fever (>38 degrees C) and myalgia were noted. Serious complications increasing mortality and morbidity were not found. The follow-up study with magnetic resonance imaging 4-6 months after injury showed slight enhancement within the zone of BMT. Syrinx formation was not definitely found. BMT and GM-CSF administration represent a safe protocol to efficiently manage SCI patients, especially those with acute complete injury. To demonstrate the full therapeutic value of this protocol, long-term and more comprehensive case-control clinical studies are required.

  5. Bone Marrow Diseases

    MedlinePlus

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains stem cells. The stem cells can ... the platelets that help with blood clotting. With bone marrow disease, there are problems with the stem ...

  6. A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254

    PubMed Central

    Furman, Richard R.; Grossbard, Michael L.; Johnson, Jeffrey L.; Pecora, Andrew L.; Cassileth, Peter A.; Jung, Sin-Ho; Peterson, Bruce A.; Nadler, Lee M.; Freedman, Arnold; Bayer, Ruthee-Lu; Bartlett, Nancy L.; Hurd, David D.; Cheson, Bruce D.

    2013-01-01

    Anti-B4-blocked ricin (anti-B4-bR) is a potent immunotoxin directed against the CD 19 antigen. Previous phase I and II studies suggested a possible role for anti-B4-bR as consolidation after high-dose chemotherapy and autologous stem cell transplant. Cancer and Leukemia Group B (CALGB) 9254 is a phase III study which randomized 157 patients with B-cell lymphoma in complete remission following autologous transplant to treatment with anti-B4-bR or observation. With a median follow-up time for patients of 5.8 years, the median event-free survival for protocol treatment and observation are 2.1 and 2.9 years, respectively (p = 0.275). The median overall survival for treatment and observation are 6.1 years and not reached, respectively (p = 0.063). Therefore, no differences were found in event-free survival and overall survival between protocol treatment and observation, although there was a trend toward improved survival with observation. These data fail to support a role for anti-B4-bR as consolidative therapy after bone marrow transplant in patients with B-cell lymphoma. PMID:21275630

  7. The use of autologous neurogenically-induced bone marrow-derived mesenchymal stem cells for the treatment of paraplegic dogs without nociception due to spinal trauma

    PubMed Central

    BESALTI, Omer; AKTAS, Zeynep; CAN, Pinar; AKPINAR, Eylul; ELCIN, Ayse Eser; ELCIN, Yasar Murat

    2016-01-01

    The aim of this study was to investigate the effects of percutaneous transplanted autologous neurogenically-induced bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to external spinal trauma. Thirteen client owned dogs that had failed in improvement neurologically at least 42 days after conservative management, decompression and decompression-stabilization were included in the study. Each dog received two doses of autologous 5.0 × 106 NIBM-MSCs suspension, which were positive to 2′,3′-Cyclic-nucleotide-3′-phosphodiesterase (CNPase) and Microtubule-associated protein 2 (MAP-2), as well as to Glial fibrillary acidic protein (GFAP) and beta III tubulin. The cells were injected into the spinal cord through the hemilaminectomy or laminectomy defects percutaneously with 21 days interval for 2 times. The results were evaluated using Texas Spinal Cord Injury Scale (TSCIS), somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) at the admission time, cell transplantation procedures and during 2, 5, 7 and 12th months after the second cell transplantation. Improvement after cell transplantation in gait, nociception, proprioception, SEP and MEP results was observed in just 2 cases, and only gait score improvement was seen in 6 cases, and no improvement was recorded in 5 cases. All progresses were observed until 2nd month after the second cell transplantation, however, there was no improvement after this period. In conclusion, percutaneous transplantation of autologous NIBM-MSCs is a promising candidate modality for cases with spinal cord injury after spinal trauma and poor prognosis. PMID:27301583

  8. Repair of osteochondral defects with in vitro engineered cartilage based on autologous bone marrow stromal cells in a swine model

    PubMed Central

    He, Aijuan; Liu, Lina; Luo, Xusong; Liu, Yu; Liu, Yi; Liu, Fangjun; Wang, Xiaoyun; Zhang, Zhiyong; Zhang, Wenjie; Liu, Wei; Cao, Yilin; Zhou, Guangdong

    2017-01-01

    Functional reconstruction of large osteochondral defects is always a major challenge in articular surgery. Some studies have reported the feasibility of repairing articular osteochondral defects using bone marrow stromal cells (BMSCs) and biodegradable scaffolds. However, no significant breakthroughs have been achieved in clinical translation due to the instability of in vivo cartilage regeneration based on direct cell-scaffold construct implantation. To overcome the disadvantages of direct cell-scaffold construct implantation, the current study proposed an in vitro cartilage regeneration strategy, providing relatively mature cartilage-like tissue with superior mechanical properties. Our strategy involved in vitro cartilage engineering, repair of osteochondral defects, and evaluation of in vivo repair efficacy. The results demonstrated that BMSC engineered cartilage in vitro (BEC-vitro) presented a time-depended maturation process. The implantation of BEC-vitro alone could successfully realize tissue-specific repair of osteochondral defects with both cartilage and subchondral bone. Furthermore, the maturity level of BEC-vitro had significant influence on the repaired results. These results indicated that in vitro cartilage regeneration using BMSCs is a promising strategy for functional reconstruction of osteochondral defect, thus promoting the clinical translation of cartilage regeneration techniques incorporating BMSCs. PMID:28084417

  9. Stem Cell Ophthalmology Treatment Study (SCOTS): improvement in serpiginous choroidopathy following autologous bone marrow derived stem cell treatment

    PubMed Central

    Weiss, Jeffrey N.; Benes, Susan C.; Levy, Steven

    2016-01-01

    We report results in a 77-year-old male patient with visual loss from long-standing serpiginous choroidopathy treated with bone marrow derived stem cells (BMSC) within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and the largest ophthalmology stem cell study registered at the National Institutes of Health to date (ClinicalTrials.gov Identifier: NCT01920867). Eight months after treatment by a combination of retrobulbar, subtenon, intravitreal and intravenous injection of BMSC, the patient's best corrected Snellen acuity improved from 20/80– to 20/60+1 in the right eye and from 20/50– to 20/20–3 in the left eye. The Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity continued to improve over the succeeding 8 months and the optical coherence tomography macular volume increased. The increases in visual acuity and macular volume are encouraging and suggest that the use of BMSC as provided in SCOTS may be a viable approach to treating serpiginous choroidopathy. PMID:27857759

  10. Prediction of Limb Salvage after Therapeutic Angiogenesis by Autologous Bone Marrow Cell Implantation in Patients with Critical Limb Ischemia

    PubMed Central

    Tara, Shuhei; Miyamoto, Masaaki; Takagi, Gen; Fukushima, Yoshimitsu; Kirinoki-ichikawa, Sonoko; Takano, Hitoshi; Takagi, Ikuyo; Mizuno, Hiroshi; Yasutake, Masahiro; Kumita, Shinichiro; Mizuno, Kyoichi

    2011-01-01

    Purpose: Despite advances in therapeutic angiogenesis by bone marrow cell implantation (BMCI), limb amputation remains a major unfavorable outcome in patients with critical limb ischemia (CLI). We sought to identify predictor(s) of limb salvage in CLI patients who received BMCI. Materials and Methods: Nineteen patients with CLI who treated by BMCI were divided into two groups; four patients with above-the-ankle amputation by 12 weeks after BMCI (amputation group) and the remaining 15 patients without (salvage group). We performed several blood-flow examinations before BMCI. Ankle-brachial index (ABI) was measured with the standard method. Transcutaneous oxygen tension (TcPO2) was measured at the dorsum of the foot, in the absence (baseline) and presence (maximum TcPO2) of oxygen inhalation. 99mtechnetium-tetrofosmin (99mTc-TF) perfusion index was determined at the foot and lower leg as the ratio of brain. Results: Maximum TcPO2 (p = 0.031) and 99mTc-TF perfusion index in the foot (p = 0.0068) was significantly higher in the salvage group than in the amputation group. Receiver operating characteristic (ROC) curve analysis identified maximum TcPO2 and 99mTc-TF perfusion index in the foot as having high predictive accuracy for limb salvage. Conclusion: Maximum TcPO2 and 99mTc-TF perfusion index in the foot are promising predictors of limb salvage after BMCI in CLI. PMID:23555423

  11. Intracoronary autologous bone marrow-derived mononuclear cell transplantation improves coronary collateral vessel formation and recruitment capacity in patients with ischemic cardiomyopathy: a combined hemodynamic and scintigraphic approach.

    PubMed

    Tayyareci, Yelda; Sezer, Murat; Umman, Berrin; Besisik, Sevgi; Mudun, Ayse; Sanli, Yasemin; Oncul, Aytac; Gurses, Nuray; Sargin, Deniz; Meric, Mehmet; Nisanci, Yilmaz

    2008-01-01

    This study investigated the effects of intracoronary autologous bone marrow-derived mononuclear cell (BMC) transplantation on coronary microcirculation. Fifteen patients with ischemic cardiomyopathy were treated by intracoronary infusion of BMCs via the patent infarct-related artery. The thermodilution-derived coronary flow reserve, index of microvascular resistance, pressure-derived collateral flow index, and coronary wedge pressure were measured at baseline and at 6 months. Successive balloon inflations during BMC transplantation were performed to observe the recruitment in pressure-derived collateral flow index and coronary wedge pressure, and the percentage changes between baseline and 6 months were calculated. The mean (SD) coronary flow reserve increased from 1.3 (0.4) to 2.1 (0.5), and the mean (SD) index of microvascular resistance decreased from 44.9 (24.4) to 21.2 (14.1) (P = .001 for both). The mean (SD) improvement in pressure-derived collateral flow index (from 0.14 [0.05] to 0.22 [0.08]) was also statistically significant (P = .001). Similarly, the percentage improvements in pressure-derived collateral flow index and coronary wedge pressure were statistically significant (P = .01 for both). The percentage improvement in perfusion assessed by single-photon emission computed tomography strongly correlated with the percentage changes in pressure-derived collateral flow index (r = 0.88, P = .001) and coronary wedge pressure (r = 0.69, P = .01). These results demonstrate for the first time (to our knowledge) that intracoronary autologous BMC transplantation improves coronary collateral vessel formation and recruitment capacity in human subjects.

  12. Kinetics of erythrogenesis after bone marrow transplantation.

    PubMed

    Lazarus, H M; Chahine, A; Lacerna, K; Wamble, A; Iaffaldano, C; Straight, M; Rabinovitch, A; Schimenti, K J; Jacobberger, J

    1992-04-01

    To determine the kinetics of bone marrow erythrogenesis after bone marrow transplantation, the authors counted reticulocytes (by blood smear and flow cytometry) and compared those data with neutrophil and platelet recovery in 23 consecutive bone marrow transplant patients. The earliest indication of marrow recovery after allogeneic and autologous bone marrow transplantation was defined as the second increasing cell count after the lowest recorded count, provided that the trend continued upward. Recovery of marrow function was detected earlier in 10 of 23 patients using reticulocyte counts than by either neutrophil or platelet count alone. Specifically, in 8 of these 10 patients, recovery of erythropoiesis was determined earlier by flow cytometric examination than by the blood smear method. On the other hand, combining the data using the earliest value of platelet, neutrophil, and reticulocyte counts indicated that the mean day of recovery in our patient population was determined to be 12.1 +/- 4 days after marrow infusion. In patients undergoing autologous and allogeneic bone marrow transplantation, serial neutrophil and reticulocyte count determinations are complementary in early clinical detection of successful engraftment.

  13. Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease

    SciTech Connect

    Tait, R.C.; Burnett, A.K.; Robertson, A.G.; McNee, S.; Riyami, B.M.; Carter, R.; Stevenson, R.D. )

    1991-06-01

    Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, as measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients.

  14. The effect of autologous bone marrow mononuclear cell transplantation on the survival duration in Amyotrophic Lateral Sclerosis - a retrospective controlled study.

    PubMed

    Sharma, Alok K; Sane, Hemangi M; Paranjape, Amruta A; Gokulchandran, Nandini; Nagrajan, Anjana; D'sa, Myola; Badhe, Prerna B

    2015-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disorder with fatal prognosis. Cellular therapy has been studied for ALS in various animal models and these advances have highlighted its potential to be a treatment modality. This is a retrospective controlled cohort study of total 57 patients. Out of these, 37 patients underwent autologous bone marrow mononuclear cell transplantation in addition to standard rehabilitation and Riluzole. Control group consisted of 20 patients who did not receive cell transplantation. The survival duration since the onset of the disease for both the groups was computed using a Kaplan-Meier Survival analysis and compared using log-rank test. Effect of age at onset, type of onset and lithium on survival duration in the intervention group was analyzed. Mean survival duration of patients in intervention group was 87.76 months which was higher than the control group mean survival duration of 57.38 months. Survival duration was significantly (p = 0.039) higher in people with the onset of the disease below 50 years of age. Limb onset and lithium also showed positive influence on the survival duration. Mean survival duration of the intervention group was also higher than the survival duration of ALS patients in previous epidemiological studies. In addition to the standard treatment with Riluzole, early intervention with combination of BMMNCs transplantation and Lithium may have a positive effect on the survival duration in ALS. Prospective randomized controlled studies with a larger sample size and rigorous methodology are required for conclusive findings.

  15. Role of parenteral antibiotherapy in gastrointestinal tract flora suppression. A study in children treated with high-dose chemotherapy and autologous bone marrow transplantation.

    PubMed

    Chastagner, P; Hartmann, O; Tancrede, C; Kalifa, C; Patte, C; Flamant, F; Lemerle, J

    1989-07-01

    In order to determine the effect of parenteral antibiotherapy on the fecal flora in patients with profound and prolonged granulocytopenia, we initiated a prospective study of 62 cases of autologous bone marrow transplantation following high-dose chemotherapy. All patients were children from 2 to 18 years old, isolated in a protective environment, receiving a diet low in viable microbial content but no oral non-absorbable prophylactic antibiotics to decontaminate the gastrointestinal tract. Bacteriological analysis of fecal flora was conducted at least once a week before and during parenteral antibiotherapy, administered at the first greater than 38 degrees C febrile episode in these granulocytopenic patients (granulocyte count less than 0.5 X 10(9)/l). The 58 evaluable patients fell into three groups with regard to the systemic antibiotherapy: group A (n = 16): moxalactam + mezlocillin; group B (n = 15): moxalactam + tobramycin; and group C (n = 27): cefotaxime plus gentamicin. Fecal flora suppression was observed in 51/58 cases (88%) (group A: 15/16, group B: 13/15, group C: 23/27). It always occurred within 5 days of initiating parenteral antibiotherapy and persisted in 88% of the 51 patients over the whole period of systemic antibiotherapy. During the latter, fecal recolonization was observed in seven cases (12%), always by Enterobacteriaceae sensitive to the prescribed systemic antibiotherapy, never responsible for septicemia. Since parenteral antibiotherapy alone was able to suppress the gastrointestinal tract flora, the effects of this treatment should be considered in all trials of digestive tract decontamination.

  16. Effect of molecular structure on the performance of triarylmethane dyes as therapeutic agents for photochemical purging of autologous bone marrow grafts from residual tumor cells.

    PubMed

    Indig, G L; Anderson, G S; Nichols, M G; Bartlett, J A; Mellon, W S; Sieber, F

    2000-01-01

    Extensively conjugated cationic molecules with appropriate structural features naturally accumulate into the mitochondria of living cells, a phenomenon typically more prominent in tumor than in normal cells. Because a variety of tumor cells also retain pertinent cationic structures for longer periods of time compared with normal cells, mitochondrial targeting has been proposed as a selective therapeutic strategy of relevance for both chemotherapy and photochemotherapy of neoplastic diseases. Here we report that the triarylmethane dye crystal violet stains cell mitochondria with efficiency and selectivity, and is a promising candidate for photochemotherapy applications. Crystal violet exhibits pronounced phototoxicity toward L1210 leukemia cells but comparatively small toxic effects toward normal hematopoietic cells (murine granulocyte-macrophage progenitors, CFU-GM). On the basis of a comparative examination of chemical, photochemical, and phototoxic properties of crystal violet and other triarylmethane dyes, we have identified interdependencies between molecular structure, and selective phototoxicity toward tumor cells. These structure-activity relationships represent useful guidelines for the development of novel purging protocols to promote selective elimination of residual tumor cells from autologous bone marrow grafts with minimum toxicity to normal hematopoietic stem cells.

  17. Percutaneous Autologous Bone Marrow-Derived Mesenchymal Stromal Cell Implantation Is Safe for Reconstruction of Human Lower Limb Long Bone Atrophic Nonunion

    PubMed Central

    Emadedin, Mohsen; Labibzadeh, Narges; Fazeli, Roghayeh; Mohseni, Fatemeh; Hosseini, Seyedeh Esmat; Moghadasali, Reza; Mardpour, Soura; Azimian, Vajiheh; Goodarzi, Alireza; Ghorbani Liastani, Maede; Mirazimi Bafghi, Ali; Baghaban Eslaminejad, Mohamadreza; Aghdami, Nasser

    2017-01-01

    Objective Nonunion is defined as a minimum of a 9-month period of time since an injury with no visibly progressive signs of healing for 3 months. Recent studies show that application of mesenchymal stromal cells (MSCs) in the laboratory setting is effective for bone regeneration. Animal studies have shown that MSCs can be used to treat nonunions. For the first time in an Iranian population, the present study investigated the safety of MSC implantation to treat human lower limb long bone nonunion. Materials and Methods It is a prospective clinical trial for evaluating the safety of using autologus bone marrow derived mesenchymal stromal cells for treating nonunion. Orthopedic surgeons evaluated 12 patients with lower limb long bone nonunion for participation in this study. From these, 5 complied with the eligibility criteria and received MSCs. Under fluoroscopic guidance, patients received a one-time implantation of 20-50×106 MSCs into the nonunion site. All patients were followed by anterior-posterior and lateral X-rays from the affected limb, in addition to hematological, biochemical, and serological laboratory tests obtained before and 1, 3, 6, and 12 months after the implantation. Possible adverse effects that included local or systemic, serious or non-serious, and related or unrelated effects were recorded during this time period. Results From a safety perspective, all patients tolerated the MSCs implantation during the 12 months of the trial. Three patients had evidence of bony union based on the after implantation Xrays. Conclusion The results have suggested that implantation of bone marrow-derived MSCs is a safe treatment for nonunion. A double-blind, controlled clinical trial is required to assess the efficacy of this treatment (Registration Number: NCT01206179). PMID:28367426

  18. Aspiration and Biopsy: Bone Marrow

    MedlinePlus

    ... Your 1- to 2-Year-Old Aspiration and Biopsy: Bone Marrow KidsHealth > For Parents > Aspiration and Biopsy: Bone Marrow A A A What's in this ... ósea What It Is Bone marrow aspirations and biopsies are performed to examine bone marrow, the spongy ...

  19. Aspiration and Biopsy: Bone Marrow

    MedlinePlus

    ... A Week of Healthy Breakfasts Shyness Aspiration and Biopsy: Bone Marrow KidsHealth > For Teens > Aspiration and Biopsy: Bone Marrow A A A What's in this ... Questions What It Is Bone marrow aspirations and biopsies are performed to examine bone marrow, the spongy ...

  20. Bone marrow biopsy

    MedlinePlus

    ... myelodysplastic syndrome; MDS) A nerve tissue tumor called neuroblastoma Bone marrow disease that leads to an abnormal ... Hairy cell leukemia Hodgkin lymphoma Multiple myeloma Myelofibrosis Neuroblastoma Non-Hodgkin lymphoma Platelet count Polycythemia vera Primary ...

  1. Long-Term Outcome of Combined (Percutaneous Intramyocardial and Intracoronary) Application of Autologous Bone Marrow Mononuclear Cells Post Myocardial Infarction: The 5-Year MYSTAR Study

    PubMed Central

    Syeda, Bonni; Charwat, Silvia; Marzluf, Beatrice; Mascherbauer, Julia; Jakab, Andras; Zimba, Abelina; Sárközy, Márta; Pavo, Noemi; Sochor, Heinz; Graf, Senta; Lang, Irene; Maurer, Gerald; Bergler-Klein, Jutta

    2016-01-01

    Objective The long-term (5-year) outcome of early (3–6 weeks after acute myocardial infarction [AMI], BM-MNC Early group) and late (3–4 months after AMI, BM-MNC Late group) combined (percutaneous intramyocardial and intracoronary) delivery of autologous bone marrow mononuclear cells (BM-MNCs) was evaluated in patients with ejection fractions (EF) between 30–45% post-AMI. Methods Major adverse cardiac and cerebrovascular events (MACCE) and hospitalization were recorded. Left (LV) and right (RV) ventricular function were measured by transthoracic echocardiography. Cardiac magnetic resonance imaging (MRI) and myocardial single photon emission computed tomography was performed in a subgroup of patients. Pre-cell therapy myocardial voltage values of treated areas (assessed by NOGA mapping) were correlated with clinical outcome. Results Five-year MACCE incidences (7.4%. vs 24.1%) and the composite of all adverse events (11.1% vs 27.6%) were not different between the Early and Late treatment groups. The significant LV-EF increase at 1-year follow-up was preserved at the 5-year control (from baseline to 5-year: 5.3%, 95% CI:0.5–10.1, and 5.7%, 95% CI:1.7–9.6, p<0.05 in the Early and Late groups, respectively), with no significant changes between 1- and 5-year follow-ups. Similarly, RVEF increased significantly from baseline to the 5-year follow-up (Early group: 5.4%, 95% CI:1.0–9.6; and Late group: 8.4%, 95% CI:4.5–12.3). Lower baseline levels of myocardial viability of the treated cardiac area (6.3±2.4 vs 8.2±3.0 mV, p<0.05) were associated with incidence of MACCE. Conclusions Percutaneous combined delivery of autologous BM-MNCs is feasible and safe after 5 years, and may result in sustained improvement of cardiac function at 5 years in patients with low EF post-AMI (Clinicaltrials.gov NCT01395212). PMID:27764157

  2. Effect of Transendocardial Delivery of Autologous Bone Marrow Mononuclear Cells on Functional Capacity, Left Ventricular Function, and Perfusion in Chronic Ischemic Heart Failure: The FOCUS-CCTRN Trial

    PubMed Central

    Perin, Emerson C.; Willerson, James T.; Pepine, Carl J.; Henry, Timothy D.; Ellis, Stephen G.; Zhao, David X.M.; Silva, Guilherme V.; Lai, Dejian; Thomas, James D.; Kronenberg, Marvin W.; Martin, A. Daniel; Anderson, R. David; Traverse, Jay H.; Penn, Marc S.; Anwaruddin, Saif; Hatzopoulos, Antonis K.; Gee, Adrian P.; Taylor, Doris A.; Cogle, Christopher R.; Smith, Deirdre; Westbrook, Lynette; Chen, James; Handberg, Eileen; Olson, Rachel E.; Geither, Carrie; Bowman, Sherry; Francescon, Judy; Baraniuk, Sarah; Piller, Linda B.; Simpson, Lara M.; Loghin, Catalin; Aguilar, David; Richman, Sara; Zierold, Claudia; Bettencourt, Judy; Sayre, Shelly L.; Vojvodic, Rachel W.; Skarlatos, Sonia I.; Gordon, David J.; Ebert, Ray F.; Kwak, Minjung; Moyé, Lemuel A.; Simari, Robert D.

    2013-01-01

    Context Previous studies utilizing autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy. The FOCUS protocol was designed to assess efficacy of a larger cell dose in an adequately well-powered phase II study. Objective To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular (LV) end systolic volume, or enhances maximal oxygen consumption in patients with coronary artery disease (CAD), LV dysfunction, and limiting heart failure and/or angina. Design, Setting, and Patients This is a 100 million cell, first-in-man randomized, double-blind, placebo-controlled trial was performed by the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) in symptomatic patients (NYHA II-III and/or CCS II-IV) receiving maximal medical therapy, with a left ventricular ejection fraction (LVEF)≤45%, perfusion defect by single-photon emission tomography (SPECT), and CAD not amenable to revascularization. Intervention All patients underwent bone marrow aspiration, isolation of BMCs using a standardized automated system performed locally, and transendocardial injection of 100 million BMCs or placebo (2:1 BMC: placebo). Main Outcome Measures Three co-primary endpoints assessed at 6 months were changes in (a) LV end systolic volume (LVESV) by echocardiography, (b) maximal oxygen consumption (MVO2), and (c) reversibility on SPECT. Secondary measures included other SPECT measures, magnetic resonance imaging (MRI), echocardiography, clinical improvement, and major adverse cardiac events (MACE). Phenotypic and functional analyses of the cell product were performed by the CCTRN Biorepository lab. Results Of 153 consented patients, a total of 92 (82 men; average age, 63 years) were randomized (n= 61 BMC, 31 placebo) at 5 sites between April 29, 2009 and April 18, 2011. Changes in LVESV index

  3. Psycholegal issues in sibling bone marrow donation.

    PubMed

    Weisz, Victoria

    1992-01-01

    The only hope of survival for children with a number of life-threatening illnesses is a successful bone marrow transplant (BMT). Unlike the treatment source for most therapies, the raw material for transplant therapy comes from a human being. Although many BMTs are autologous, utilizing the patient's own bone marrow, a large percentage of childhood BMTs rely on bone marrow from children or adolescents who are biological siblings to the sick child. Medical and legal systems are confronted with a dilemma when healthy children are needed to undergo minimally risky, yet somewhat painful, procedures for the benefit of their critically ill siblings. This article reviews legal issues involved in sibling bone marrow donation and psychological research that is relevant to those issues. The article concludes with proposed directions for future psycholegal research and a discussion of ethical issues that are not amenable to empirical investigation.

  4. Improved outcomes after autologous bone marrow transplantation for children with relapsed or refractory Hodgkin lymphoma: twenty years experience at a single institution.

    PubMed

    Garfin, Phillip M; Link, Michael P; Donaldson, Sarah S; Advani, Ranjana H; Luna-Fineman, Sandra; Kharbanda, Sandhya; Porteus, Matthew; Weinberg, Kenneth I; Agarwal-Hashmi, Rajni

    2015-02-01

    The purpose of this study is to evaluate the survival of pediatric patients undergoing autologous bone marrow transplantation (auBMT) for relapsed or refractory Hodgkin lymphoma (rrHL) and to identify factors that might contribute to their outcome. We reviewed the records and clinical course of 89 consecutive rrHL patients ≤ 21 years old who underwent auBMT at Stanford Hospitals and Clinics and the Lucile Packard Children's Hospital, Stanford between 1989 and 2012. We investigated, by multiple analyses, patient, disease, and treatment characteristics associated with outcome. Endpoints were 5-year overall and event-free survival. Our findings include that cyclophosphamide, carmustine, and etoposide (CBV) as a conditioning regimen for auBMT is effective for most patients ≤ 21 years old with rrHL (5-year overall survival, 71%). Transplantation after the year 2001 was associated with significantly improved overall survival compared with our earlier experience (80% compared with 65%). Patients with multiply relapsed disease or with disease not responsive to initial therapy fared less well compared with those with response to initial therapy or after first relapse. Administration of post-auBMT consolidative radiotherapy (cRT) also appears to contribute to improved survival. We are able to conclude that high-dose chemotherapy with CBV followed by auBMT is effective for the treatment of rrHL in children and adolescents. Survival for patients who undergo auBMT for rrHL has improved significantly. This improvement may be because of patient selection and improvements in utilization of radiotherapy rather than improvements in chemotherapy. Further investigation is needed to describe the role of auBMT across the entire spectrum of patients with rrHL and to identify the most appropriate preparative regimen with or without cRT therapy in the treatment of rrHL in young patients.

  5. Bone and bone marrow: the same organ.

    PubMed

    Del Fattore, Andrea; Capannolo, Marta; Rucci, Nadia

    2010-11-01

    Interplays between bone and bone marrow are not limited to merely anatomic and histological connections, but include a tight functional correlation. Bone marrow resides within the medullary cavity of the bones and the process of hematopoiesis is regulated, at least in part, by bone cells. Moreover, osteoclasts and osteoblasts derive from precursors of hematopoietic and mesenchymal origin, respectively, both residing within the bone marrow. Alterations in one of these components typically cause impairment in the other, so diseases of the bone marrow compartment often affect the bone and vice versa. All these findings could make us to speculate that bone and bone marrow are not two separate districts, but can be considered as the two elements of the same unique functional unit, the bone-bone marrow organ. Here we will describe histological and functional interplays between bone and bone marrow, and will illustrate some diseases in which this tight correlation is evident.

  6. Bone-marrow transplant - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100112.htm Bone-marrow transplant - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Bone-marrow is a soft, fatty tissue found inside of ...

  7. Efficacy of Autologous Bone Marrow-Derived Mesenchymal Stem Cell and Mononuclear Cell Transplantation in Type 2 Diabetes Mellitus: A Randomized, Placebo-Controlled Comparative Study.

    PubMed

    Bhansali, Shobhit; Dutta, Pinaki; Kumar, Vinod; Yadav, Mukesh Kumar; Jain, Ashish; Mudaliar, Sunder; Bhansali, Shipra; Sharma, Ratti Ram; Jha, Vivekanand; Marwaha, Neelam; Khandelwal, Niranjan; Srinivasan, Anand; Sachdeva, Naresh; Hawkins, Meredith; Bhansali, Anil

    2017-04-01

    Drugs targeting β-cells have provided new options in the management of T2DM; however, their role in β-cell regeneration remains elusive. The recent emergence of cell-based therapies such as autologous bone marrow-derived mesenchymal stem cells (ABM-MSCs) and mononuclear cells (ABM-MNCs) seems to offer a pragmatic approach to augment β-cell function/mass. This study aims to examine the efficacy and safety of ABM-MSC and ABM-MNC transplantation in T2DM and explores alterations in glucose-insulin homeostasis by metabolic studies. Thirty patients of T2DM with duration of disease ≥5 years, receiving triple oral antidiabetic drugs along with insulin (≥0.4 IU/Kg/day) with HbA1c ≤7.5%(≤58.0 mmol/mol), were randomized to receive ABM-MSCs or ABM-MNCs through targeted approach and a sham procedure (n = 10 each). The primary endpoint was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c <7.0% (<53.0 mmol/mol) during 1-year follow-up. Six of 10 (60%) patients in both the ABM-MSC and ABM-MNC groups, but none in the control group, achieved the primary endpoint. At 12 months, there was a significant reduction in insulin requirement in ABM-MSC (P < 0.05) and ABM-MNC groups (P < 0.05), but not in controls (P = 0.447). There was a significant increase in second-phase C-peptide response during hyperglycemic clamp in the ABM-MNC (P < 0.05) group, whereas a significant improvement in insulin sensitivity index (P < 0.05) accompanied with an increase in insulin receptor substrate-1 gene expression was observed in the ABM-MSC group. In conclusion, both ABM-MSCs and ABM-MNCs result in sustained reduction in insulin doses in T2DM. Improvement in insulin sensitivity with MSCs and increase in C-peptide response with MNCs provide newer insights in cell-based therapies.

  8. Therapeutic effects of autologous bone marrow cells and metabolic intervention in the ischemic hindlimb of spontaneously hypertensive rats involve reduced cell senescence and CXCR4/Akt/eNOS pathways.

    PubMed

    de Nigris, Filomena; Balestrieri, Maria Luisa; Williams-Ignarro, Sharon; D'Armiento, Francesco P; Lerman, Lilach O; Byrns, Russell; Crimi, Ettore; Palagiano, Antonio; Fatigati, Gennaro; Ignarro, Louis J; Napoli, Claudio

    2007-10-01

    Peripheral arterial disease (PAD) is a major health problem, especially when associated with severe hypertension. Administration of autologous bone marrow cells (BMCs) is emerging as a novel intervention to induce neoangiogenesis in ischemic limb models and in patients with PAD. This study evaluates the neovascularization capacity of BMCs alone or in combination with metabolic cotreatment (0.8% vitamin E, 0.05% vitamin C, and 5% of L-arginine) in a rat model of ischemic hindlimbs of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Molecular mechanisms were investigated in bone marrow-derived endothelial progenitor cells (BM-EPC) derived from rats. BMC therapy increased blood flow and capillary densities and Ki67 proliferative marker, and it decreased interstitial fibrosis. These effects were amplified by metabolic cotreatment, an intervention that induces vascular protection at least partly through the nitric oxide (NO)/endothelial nitric oxide synthase (eNOS) pathway, reduction of systemic oxidative stress, and macrophage activation. In addition, BMC therapy alone and, more consistently, in combination with metabolic treatment, ameliorated BM-EPC functional activity via decreased cellular senescence and improved homing capacity by increasing CXCR4-expression levels. These data suggest potential therapeutic effects of autologous BMCs and metabolic treatment in hypertensive PAD patients.

  9. Post-5-fluorouracil human marrow: stem cell characteristics and renewal properties after autologous marrow transplantation.

    PubMed

    Stewart, F M; Temeles, D; Lowry, P; Thraves, T; Grosh, W W; Quesenberry, P J

    1993-05-01

    The effect of 5-fluorouracil (5-FU) pretreatment on human bone marrow (BM) progenitor/stem cells and recovery of hematopoiesis after autologous marrow transplant was studied. Twenty-one patients were treated with 5-FU (15 mg/kg to 45 mg/kg) intravenously (IV) for 1 to 3 days administered 6 to 22 days before BM harvest. Post-FU marrow was infused into 15 patients after high-dose cyclophosphamide, carmustine (BCNU), and VP-16 (CBV). Seventeen patients (historical controls) were treated with CBV and autologous BM transplantation but did not receive 5-FU before marrow harvest. The groups were comparable for diagnosis and prior therapy. In the 5-FU-treated group and control group, median recovery times for platelet count to 50,000/mm3 were 20 and 30 days, respectively (P = .007), and for platelet count to 100,000/mm3, 23 and 38 days, respectively (P = .007), while neutrophil recovery was not significantly altered. In vitro cultures with 1 to 7 growth factors (interleukin-1 [IL-1], IL-3, IL-4, IL-6, colony-stimulating factor-1 [CSF-1], granulocyte-macrophage colony-stimulating factor [GM-CSF], and G-CSF) were performed. In 8 of 10 patients whose marrow was studied before and after 5-FU treatment, the numbers of CFU-C responsive to the combination of GM-CSF and IL-3 was increased 6.15-fold by 5-FU pretreatment. In 4 of these patients, thymidine suicide of GM-CSF- and IL-3-stimulated CFU-C ranged from 17% to 42%. High proliferative potential colony-forming cell (HPP-CFC) was observed in low frequency in normal marrow and patient's marrow before 5-FU treatment. In 11 of 16 patients pretreated with 5-FU, increased numbers of HPP-CFC were noted. GM-CSF and IL-3 interacted synergistically to stimulate HPP-CFC. Multifactor combinations, especially GM-CSF + G-CSF + IL-3 + IL-6 + IL-1 + CSF-1 did not increase total colony count or classic HPP-CFC but did result in altered morphology, producing huge, loose colonies. The marrow from patients pretreated with 5-FU is enriched with

  10. In vitro incubation of bone marrow and peripheral stem cells with vincristine and methylprednisolone: functional T-cell depletion for haploidentical and autologous transplants.

    PubMed

    Fragonas, E; Perticarari, S; Presani, G; Rabusin, M; Andolina, M; Mangiarotti, M A

    2000-11-01

    A mismatched bone marrow transplantation is feasible only if the donor's marrow lymphocytes are eliminated from the graft. This can be achieved by several methods, but all have the disadvantage of inducing a long-lasting immune deficiency while the risk of graft rejection and leukemic relapse increase. We use a sort of functional T-cell depletion by treating the cells with vincristine and methylprednisolone. This method is surely the cheapest and has allowed us to perform 60 transplants with a tolerable risk of GVHD. The treatment of the donor's lymphocytes has already been demonstrated to be able to block the mixed lymphocyte culture reaction in vitro. In this experiment Th1 and Th2 activities were almost completely blocked without reduction of lymphocyte viability and apoptosis induction.

  11. Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three-Dimensional Woven-Fabric Scaffold for Periodontitis

    PubMed Central

    Baba, Shunsuke; Komuro, Akira; Yotsui, Yoritaka; Umeda, Makoto; Shimuzutani, Kimishige; Nakamura, Sayaka

    2016-01-01

    Regenerative medicine is emerging as a promising option, but the potential of autologous stem cells has not been investigated well in clinical settings of periodontal treatment. In this clinical study, we evaluated the safety and efficacy of a new regenerative therapy based on the surgical implantation of autologous mesenchymal stem cells (MSCs) with a biodegradable three-dimensional (3D) woven-fabric composite scaffold and platelet-rich plasma (PRP). Ten patients with periodontitis, who required a surgical procedure for intrabony defects, were enrolled in phase I/II trial. Once MSCs were implanted in each periodontal intrabony defect, the patients were monitored during 36 months for a medical exam including laboratory tests of blood and urine samples, changes in clinical attachment level, pocket depth, and linear bone growth (LBG). All three parameters improved significantly during the entire follow-up period (p < 0.0001), leading to an average LBG of 4.7 mm after 36 months. Clinical mobility measured by Periotest showed a decreasing trend after the surgery. No clinical safety problems attributable to the investigational MSCs were identified. This clinical trial suggests that the stem cell therapy using MSCs-PRP/3D woven-fabric composite scaffold may constitute a novel safe and effective regenerative treatment option for periodontitis. PMID:27990164

  12. A Randomized Comparative Study on the Efficacy of Intracoronary Infusion of Autologous Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells in Patients With Dilated Cardiomyopathy.

    PubMed

    Xiao, Wentao; Guo, Suping; Gao, Chuanyu; Dai, Guoyou; Gao, Yongjv; Li, Muwei; Wang, Xianpei; Hu, Dayi

    2017-02-13

    Stem cell therapy has shown therapeutic benefit in dilated cardiomyopathy (DCM), but doubt remains about the most appropriate stem cell subpopulation. The current study compared the efficacy of intracoronary administration of bone marrow mononuclear cells (BMMC) or mesenchymal stem cells (BMSC) in patients with DCM.Fifty-three patients with DCM and reduced (< 40%) left ventricular ejection fraction (LVEF), were randomized to intracoronary infusion of BMMC (BMMC group, n = 16) or BMSC (BMSC group, n = 17) or equal volume normal saline (CTRL group, n = 20). LVEF, New York Heart Association (NYHA) class, left ventricular end-diastolic diameter (LVEDd), and myocardial perfusion were assessed at baseline and at 3-month and 12-month follow-ups. Major adverse cardiovascular events (MACE) were also recorded.At the 3-month follow-up, LVEF, NYHA class, and myocardial perfusion had improved significantly in the BMSC group (P = 0.004, 0.020 and 0.019, respectively) along with significant changes in LVEF and NYHA class in the BMMC group compared with CTRL (P = 0.042 and 0.047, respectively), however, LVEDd remained unchanged. In comparison with CTRL, LVEF, NYHA class, and myocardial perfusion improved significantly in the BMSC group at the 12-month follow-up (P = 0.005, 0.050 and 0.038 respectively), but not in the BMMC group (P > 0.05). There were no significant differences between the transplantation groups during follow-up (P > 0.05). There were no differences in MACE among the 3 groups (P = 0.817).Intracoronary bone marrow stem cell transplantation in DCM is safe and effective, while BMSC and BMMC infusion possess comparable effectiveness.

  13. What Are Bone Marrow Tests?

    MedlinePlus

    ... for people with certain bleeding disorders such as hemophilia. Bone marrow tests can be done in a ... reading Anemia Aplastic Anemia Blood Tests Clinical Trials Hemophilia Thrombocythemia and Thrombocytosis Thrombocytopenia Rate This Content: Updated: ...

  14. Aspiration and Biopsy: Bone Marrow

    MedlinePlus

    ... in determining treatment and prognosis) viral, bacterial, or fungal infections in the bone marrow that might be causing lasting fever or other symptoms certain genetic diseases (such as lipid storage diseases) They also ...

  15. Aspiration and Biopsy: Bone Marrow

    MedlinePlus

    ... in determining treatment and prognosis) viral, bacterial, or fungal infections in the bone marrow that might be causing a lasting fever or other symptoms certain genetic diseases (such as lipid storage diseases) They also ...

  16. Autologous bone marrow mesenchymal stem cells associated with tantalum rod implantation and vascularized iliac grafting for the treatment of end-stage osteonecrosis of the femoral head.

    PubMed

    Zhao, Dewei; Liu, Baoyi; Wang, Benjie; Yang, Lei; Xie, Hui; Huang, Shibo; Zhang, Yao; Wei, Xiaowei

    2015-01-01

    Tantalum rod implantation with vascularized iliac grafting has been reported to be an effective method for the treatment of young patients with osteonecrosis of the femoral head (ONFH) to avert the need for total hip arthroplasty (THA). However, there have been unsatisfactory success rates for end-stage ONFH. The authors describe a modified technique using bone marrow mesenchymal stem cells (BMMSCs) associated with porous tantalum rod implantation combined with vascularized iliac grafting for the treatment of end-stage ONFH. A total of 24 patients (31 hips) with end-stage ONFH were treated with surgery; ARCO IIIc stage was observed in 19 hips and ARCO IV stage was observed in 12 hips. All patients were followed for a mean time of 64.35 ± 13.03 months (range 26-78). Operations on only five hips were converted to THA. The joint-preserving success rate of the entire group was 89.47% for ARCO stage IIIc and 75% for ARCO stage IV. The mean Harris hip score of the 31 hips improved significantly from 38.74 ± 5.88 points (range 22-50) to 77.23 ± 14.75 points (range 33-95). This intervention was safe and effective in delaying or avoiding total hip replacement for end-stage ONFH.

  17. Autologous Bone Marrow Mesenchymal Stem Cells Associated with Tantalum Rod Implantation and Vascularized Iliac Grafting for the Treatment of End-Stage Osteonecrosis of the Femoral Head

    PubMed Central

    Zhao, Dewei; Liu, Baoyi; Wang, Benjie; Yang, Lei; Xie, Hui; Huang, Shibo; Zhang, Yao; Wei, Xiaowei

    2015-01-01

    Tantalum rod implantation with vascularized iliac grafting has been reported to be an effective method for the treatment of young patients with osteonecrosis of the femoral head (ONFH) to avert the need for total hip arthroplasty (THA). However, there have been unsatisfactory success rates for end-stage ONFH. The authors describe a modified technique using bone marrow mesenchymal stem cells (BMMSCs) associated with porous tantalum rod implantation combined with vascularized iliac grafting for the treatment of end-stage ONFH. A total of 24 patients (31 hips) with end-stage ONFH were treated with surgery; ARCO IIIc stage was observed in 19 hips and ARCO IV stage was observed in 12 hips. All patients were followed for a mean time of 64.35 ± 13.03 months (range 26–78). Operations on only five hips were converted to THA. The joint-preserving success rate of the entire group was 89.47% for ARCO stage IIIc and 75% for ARCO stage IV. The mean Harris hip score of the 31 hips improved significantly from 38.74 ± 5.88 points (range 22–50) to 77.23 ± 14.75 points (range 33–95). This intervention was safe and effective in delaying or avoiding total hip replacement for end-stage ONFH. PMID:25802840

  18. Autologous bone marrow stromal cell transplantation as a treatment for acute radiation enteritis induced by a moderate dose of radiation in dogs.

    PubMed

    Xu, Wenda; Chen, Jiang; Liu, Xu; Li, Hongyu; Qi, Xingshun; Guo, Xiaozhong

    2016-05-01

    Radiation enteritis is one of the most common complications of cancer radiotherapy, and the development of new and effective measures for its prevention and treatment is of great importance. Adult bone marrow stromal stem cells (ABMSCs) are capable of self-renewal and exhibit low immunogenicity. In this study, we investigated ABMSC transplantation as a treatment for acute radiation enteritis. We developed a dog model of acute radiation enteritis using abdominal intensity-modulated radiation therapy in a single X-ray dose of 14 Gy. ABMSCs were cultured in vitro, identified via immunofluorescence and flow cytometry, and double labeled with CM-Dil and superparamagnetic iron oxide (SPIO) before transplantation, which took place 48 hours after abdominal irradiation in a single fraction. The dog model of acute radiation enteritis was transplanted with cultured ABMSCs labeled with CM-Dil and SPIO into the mesenteric artery through the femoral artery. Compared with untreated control groups, dogs treated with ABMSCs exhibited substantially longer survival time and improved relief of clinical symptoms. ABMSC transplantation induced the regeneration of the intestinal epithelium and the recovery of intestinal function. Furthermore, ABMSC transplantation resulted in elevated serum levels of the anti-inflammatory cytokine interleukin-11 (IL10) and intestinal radioprotective factors, such as keratinocyte growth factor, basic fibroblast growth factor-2, and platelet-derived growth factor-B while reducing the serum level of the inflammatory cytokine IL17. ABMSCs induced the regeneration of the intestinal epithelium and regulated the secretion of serum cytokines and the expression of radioprotective proteins and thus could be beneficial in the development of novel and effective mitigators of and protectors against acute radiation enteritis.

  19. Successful treatment of primary extramedullary leukemia (EML) of the uterus with radical surgery, chemotherapy, autologous bone marrow transplantation (BMT) and prophylactic local irradiation.

    PubMed

    Huter, O; Brezinka, C; Nachbaur, D; Schwaighofer, H; Lang, A; Niederwieser, D

    1996-09-01

    Extramedullary myeloid cell tumors are rare manifestations of acute nonlymphocytic leukemia (ANLL). While many advances in diagnosis have been made, dilemmas remain concerning the treatment of this disease. In primary extramedullary leukemia (EML) most reports agree upon a local therapy followed by systemic chemotherapy such as is used for ANLL. However, further prophylactic local or systemic therapy with stem cell support remains controversial. A 20-year-old patient was diagnosed as having granulocytic sarcoma (GS) of the uterus without evidence of ANLL in 1991. After resection of the tumor at the uterine cervix and chemotherapy with daunorubicin 50 mg/m2 (days 1-3) and cytosine-arabinoside 200 mg/m2 (days 1-7) in September 1991, complete remission was achieved. In October 1991 cytosine-arabinoside 1000 mg/m2 every 12 h from day 1 to day 6 and amsacrine 200 mg from day 5 to day 7 were given as consolidation. Two years later relapse occurred in the adnexae. After radical hysterectomy, the same induction and consolidation chemotherapy was administrated. Subsequently, cytoxane 60 mg/m2 and fractionated total body irradiation (6 x 200 cGy) were given as conditioning and the previously cryopreserved bone marrow was reinfused. Finally, after hematopoietic engraftment, prophylactic local irradiation (4500 cGy) to the pelvis was given resulting in a disease-free long-term survival of more than 36 months after relapse. Although this experience is confined to one patient, it may contribute to the design of prospective therapeutic studies in patients with primary EML.

  20. [Normal bone marrow and common reactive alterations].

    PubMed

    Tzankov, A; Dirnhofer, S; Beham-Schmid, C

    2012-11-01

    Histological examination of bone marrow biopsies is an important and powerful diagnostic tool to assess various hematological and non-hematological disorders. Morphological examination of such biopsies requires knowledge of the composition of normal bone marrow and its variations, such as age-related changes. Diagnostic problems may arise due to poor specimen quality, insufficient sections or stainings and insufficient experience with reactive bone marrow changes which occasionally resemble neoplastic disorders. Reactive bone marrow processes can affect one or more hematopoietic cell lines, lead to disruption of the normal architecture and specifically affect the bone marrow stroma. Optimal bone marrow diagnosis requires adequately stained slides and, when needed, immunophenotyping and molecular examinations. Furthermore, rather than biopsy interpretation of other organs, pathologists routinely need clinical history information for correct interpretation and diagnosis of bone marrow changes. In this article, the normal features of bone marrow as well as the most frequent reactive bone marrow alterations are described.

  1. Engineering bone grafts with enhanced bone marrow and native scaffolds.

    PubMed

    Hung, Ben P; Salter, Erin K; Temple, Josh; Mundinger, Gerhard S; Brown, Emile N; Brazio, Philip; Rodriguez, Eduardo D; Grayson, Warren L

    2013-01-01

    The translation of tissue engineering approaches to the clinic has been hampered by the inability to find suitable multipotent cell sources requiring minimal in vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long bone medullary canals and isolating the solid marrow putty, has large quantities of stem cells and demonstrates significant potential to regenerate bone tissues. eBM, however, cannot impart immediate load-bearing mechanical integrity or maintain the gross anatomical structure to guide bone healing. Yet, its putty-like consistency creates a challenge for obtaining the uniform seeding necessary to effectively combine it with porous scaffolds. In this study, we examined the potential for combining eBM with mechanically strong, osteoinductive trabecular bone scaffolds for bone regeneration by creating channels into scaffolds for seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using a Synthes reamer-irrigator-aspirator device, analyzed histologically, and digested to extract cells and characterize their differentiation potential. To evaluate bone tissue formation, eBM was seeded into the channels in collagen-coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks, harvested and assessed for tissue distribution and bone formation. Our data demonstrates that eBM is a heterogenous tissue containing multipotent cell populations. Furthermore, coating scaffolds with a collagen hydrogel significantly enhanced cellular migration, promoted uniform tissue development and increased bone mineral deposition. These findings suggest the potential for generating customized autologous bone grafts for treating critical-sized bone defects by combining a readily available eBM cell source with decellularized trabecular bone scaffolds.

  2. 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.

  3. Role of bone marrow macrophages in controlling homeostasis and repair in bone and bone marrow niches.

    PubMed

    Kaur, Simranpreet; Raggatt, Liza Jane; Batoon, Lena; Hume, David Arthur; Levesque, Jean-Pierre; Pettit, Allison Robyn

    2017-01-01

    Macrophages, named for their phagocytic ability, participate in homeostasis, tissue regeneration and inflammatory responses. Bone and adjacent marrow contain multiple functionally unique resident tissue macrophage subsets which maintain and regulate anatomically distinct niche environments within these interconnected tissues. Three subsets of bone-bone marrow resident tissue macrophages have been characterised; erythroblastic island macrophages, haematopoietic stem cell niche macrophages and osteal macrophages. The role of these macrophages in controlling homeostasis and repair in bone and bone marrow niches is reviewed in detail.

  4. Methotrexate and bone marrow metaphases.

    PubMed

    Cunningham, J J; Potter, A M; Watmore, A E; Winfield, D A

    1988-07-15

    The efficacy of a methotrexate (MTX) block/thymidine release synchronization technique has been assessed in bone marrow cultures from patients with acute nonlymphocytic leukemia and myelodysplasia. In contrast to cultures of stimulated lymphocytes from normal individuals, no improvement in mitotic index (MI) or metaphase quality could be detected using this technique. Demonstration of an unchanged level of division in bone marrow cultures in the presence of MTX suggests that the technique is unsuitable for synchronization purposes in this tissue. The influence of preincubation prior to MTX exposure and duration of exposure to colcemid on MI and metaphase quality have also been examined.

  5. Bone scan appearances following bone and bone marrow biopsy

    SciTech Connect

    McKillop, J.H.; Maharaj, D.; Boyce, B.F.; Fogelman, I.

    1984-01-01

    Bone marrow and bone biopsies are performed not infrequently in patients referred for bone scans and represent a potential cause of a ''false positive'' focal abnormality on the bone scan. The authors have therefore examined the scan appearances in a series of patients who had undergone either sternal marrow biopsy, (Salah needle, diameter 1.2 mm) trephine iliac crest marrow biopsy (Jamshidi 11 gauge needle, diameter 3.5 mm) or a transiliac bone biopsy (needle diameter 8 mm). Of 18 patients studied 1 to 45 days after sternal marrow 17 had normal scan appearances at the biopsy site and 1 had a possible abnormality. None of 9 patients studied 4 to 19 days after trephine iliac crest marrow biopsy had a hot spot at the biopsy site. A focal scan abnormality was present at the biopsy site in 9/11 patients studied 5 to 59 days after a trans iliac bone biopsy. No resultant scan abnormality was seen in 4 patients imaged within 3 days of the bone biopsy or in 3 patients imaged 79 to 138 days after the procedure. Bone marrow biopsy of the sternum or iliac crest does not usually cause bone scan abnormalities. A focal abnormality at the biopsy site is common in patients imaged 5 days to 2 months after bone biopsy. The gauge of the needle employed in the biopsy and thus the degree of bone trauma inflicted, is likely to be main factor determining the appearance of bone scan abnormalities at the biopsy site.

  6. Structural features of bone marrow

    PubMed Central

    Romaniuk, Anatolii; Lyndina, Yuliia; Sikora, Vladyslav; Lyndin, Mykola; Karpenko, Ludmyla; Gladchenko, Oksana; Masalitin, Igor

    2016-01-01

    Purpose This article is devoted to the investigation of the structural features of the bone marrow of mature rats. Materials and methods The investigation of the structural features of the bone marrow was performed on the femurs of the mature male rats. General structure of the organ was studied with hematoxylin–eosin and Van Gieson staining of samples. Certain features of the bone marrow structure were studied using immunohistochemical method (CD3, CD79α, S100, myeloperoxidase, and cyclin D1). Results We can state that stromal–parenchymal structure is typical for the bone marrow of rats as for any other organ. The stromal component is presented with bone tissue (48.8 ± 3.3% at epiphyses), the net of blood vessels (18.7 ± 2.1%), fat tissue (11 ± 2%), fibrous tissue (0.7 ± 0.2%), and the network of reticular fibers. Hematopoietic tissue covers 20.9 ± 3.7% at the femoral epiphyses and 69.6 ± 2.2% at diaphysis. Among these tissues, myelopoiesis occupies 74.2 ± 4.7%, erythropoiesis – 24.3 ± 4.7%, and lymphopoiesis – less than 5%. Megalokaryocytes take 0.1–0.3%. Conclusion Considering the lack of significant anatomical, morphological, and histological differences of red bone marrow of rats and humans, we can state that hematopoiesis in rats takes place on the basis of the same principles as in humans, although it has certain mechanisms. PMID:28203394

  7. Magna-field irradiation and autologous marrow rescue in the treatment of pediatric solid tumors

    SciTech Connect

    Munoz, L.L.; Wharam, M.D.; Kaizer, H.; Leventhal, B.G.; Ruymann, R.

    1983-12-01

    Marrow ablative therapy has been given to pediatric patients with a variety of disseminated tumors. Eight patients with advanced neuroblastoma received autologous marrow reinfusion after intensive therapy. Three of eight are in continuous complete remission from 7 to 60 months. An additional four patients received allogeneic marrow transplantation and two remain in continuous complete response at 21 and 39 months. Intensive therapy and autologous marrow reinfusion have been applied to Ewing's sarcoma, but only preliminary results are available. Six patients with disseminated rhabdomyosarcoma and extra-osseous Ewing's sarcoma received conventional chemotherapy followed by sequential hemi-body irradiation. Four of six patients received autologous marrow rescue. Their median disease-free survival is 17 months. This preliminary experience demonstrates the feasibility of using marrow ablative therapy with autologous marrow transplantation in the treatment of pediatric solid tumors. Continuing Phase II studies are required to substantiate its efficacy.

  8. Increasing Dose of Autologous Bone Marrow Mononuclear Cells Transplantation Is Related to Stroke Outcome: Results from a Pooled Analysis of Two Clinical Trials

    PubMed Central

    Escudero, Irene; Zapata, Elena; de la Torre Laviana, Francisco Javier; Carmona, Magdalena; Piñero, Pilar; Bustamante, Alejandro; Lebrato, Lucía; Cabezas, Juan Antonio; Gonzalez, Alejandro; de Freitas, Grabriel R.; Montaner, Joan

    2016-01-01

    Background and Purpose. BM-MNC transplantation improves recovery in experimental models of ischemic stroke. Clinical trials are ongoing to test efficacy in stroke patients. However, whether cell dose is related to outcomes is not known. Methods. We performed a pooling data analysis of two pilot clinical trials with autologous BM-MNCs transplantation in ischemic stroke patients. Cell dose and route were analyzed to evaluate their relation to good outcome (m-Rankin scale [mRS] score 0–2) at 6 months. Results. Twenty-two patients were included. A median of 153 × 106 (±121 × 106) BM-MNCs was injected. Intra-arterial route was used in 77.3% of cases. A higher number of cells injected were associated with better outcomes at 180 days (390 × 106 [320–422] BM-MNCs injected in those patients with mRS of 0–2 at 6 months versus 130 × 106 [89–210] in those patients with mRS 3–6, p = 0.015). In the intra-arterially treated patients, a strong correlation between dose of cells and disability was found (r = −0.63, p = 0.006). A cut point of 310 × 106 injected cells predicted good outcome with 80% sensitivity and 88.2% specificity. Conclusions. Similar to preclinical studies, a higher dose of autologous BM-MNC was related to better outcome in stroke patients, especially when more than 310 × 106 cells are injected. Further interventional studies are warranted to confirm these data. PMID:27525011

  9. Blood and Bone Marrow Hematopoietic Stem Cells for Transplantation: A Comparative Review.

    PubMed

    Janssen; Hiemenz; Fields; Zorsky; Ballester; Goldstein; Elfenbein

    1994-05-01

    Classical bone marrow transplantation collects bone marrow from a normal individual. This is infused into a patient rendered aplastic by high-dose chemoradiotherapy. Shortcomings include a limited donor pool and morbidity and mortality from graft-vs-host and graft rejection phenomena. Autologous marrow transplantation, in which the marrow of the patient to be transplanted is harvested, cryopreserved, and stored until needed, is not so constrained. Although marrow cannot be collected from some individuals due to hypocellularity, fibrosis, or infiltration with malignant disease, the presence of peripheral blood stem cells in the circulation allows these individuals to be treated with autologous transplantation therapy. It has been postulated that these hematopoietic progenitors have advantages over bone marrow collected stem cells, including safer and less expensive collections and accelerated rates of hematopoietic recovery following high-dose therapy and stem cell reinfusion.

  10. Bone scan appearances following biopsy of bone and bone marrow

    SciTech Connect

    McKillop, J.H.; Maharaj, D.; Boyce, B.F.; Fogelman, I.

    1984-10-01

    The influence of sternal marrow aspiration, iliac crest marrow aspiration, and iliac crest bone biopsy on bone scan appearances was examined. Eighteen patients were scanned a mean of 9.9 days after sternal marrow aspiration with a Salah needle. Bone scans obtained in 9 patients a mean of 10 days aftr iliac crest trephine marrow biopsy with a Jamshidi needle showed no abnormality at the biopsy site. In 18 patients with metabolic bone disease who had undergone iliac crest bone biopsy with an 8 mm needle, a scan abnormality due to the biopsy was usually present when the interval between the biopsy and the scan was 5 days to 2 months. Patients who were scanned within 3 days of iliac crest bone biopsy or more than 2 months after biopsy had normal scan appearance at the biopsy site.

  11. Bones of contention: marrow-derived cells in myocardial regeneration.

    PubMed

    Sussman, Mark A; Murry, Charles E

    2008-06-01

    Almost 7 years have passed since the initial publication reporting that bone marrow cells regenerate infarcted myocardium. The subsequent years produced hundreds of investigations that ran the gamut of findings from validation to disproof. Undeterred by the concurrent debate, clinical trials ensued to test the safety and efficacy of bone marrow-derived cell population for autologous therapy in clinical treatment of myocardial disease. In the following conversational exchange, two scientists with distinct perspectives weigh the pros and cons of pursuing bone marrow stem cell therapy and look toward finding a consensus of where the future lies for regenerative medicine and the heart. The conclusion is that the two camps may not be as far apart as it may seem from the rancor in literature and at meetings, and the potential of one day achieving regenerative therapy is indeed a vision that both parties enthusiastically share.

  12. Prognostic Factors and a New Prognostic Index Model for Children and Adolescents with Hodgkin’s Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation: A Multicenter Study of the Turkish Pediatric Bone Marrow Transplantation Study Group

    PubMed Central

    Kesik, Vural; Ataş, Erman; Karakükcü, Musa; Aksoylar, Serap; Erbey, Fatih; Taçyıldız, Nurdan; Küpesiz, Alphan; Öniz, Haldun; Ünal, Ekrem; Kansoy, Savaş; Öztürk, Gülyüz; Elli, Murat; Kaya, Zühre; Ünal, Emel; Hazar, Volkan; Yılmaz Bengoa, Şebnem; Karasu, Gülsün; Atay, Didem; Dağdemir, Ayhan; Ören, Hale; Koçak, Ülker; Yeşilipek, M. Akif

    2016-01-01

    Objective: The prognostic factors and a new childhood prognostic index after autologous hematopoietic stem cell transplantation (AHSCT) in patients with relapsed/refractory Hodgkin’s lymphoma (HL) were evaluated. Materials and Methods: The prognostic factors of 61 patients who underwent AHSCT between January 1990 and December 2014 were evaluated. In addition, the Age-Adjusted International Prognostic Index and the Childhood International Prognostic Index (CIPI) were evaluated for their impact on prognosis. Results: The median age of the 61 patients was 14.8 years (minimum-maximum: 5-20 years) at the time of AHSCT. There were single relapses in 28 patients, ≥2 relapses in eight patients, and refractory disease in 25 patients. The chemosensitivity/chemorefractory ratio was 36/25. No pretransplant radiotherapy, no remission at the time of transplantation, posttransplant white blood cell count over 10x103/µL, posttransplant positron emission tomography positivity at day 100, and serum albumin of <2.5 g/dL at diagnosis were correlated with progression-free survival. No remission at the time of transplantation, bone marrow positivity at diagnosis, and relapse after AHSCT were significant parameters for overall survival. Conclusion: The major factors affecting the progression-free and overall survival were clearly demonstrated. A CIPI that uses a lactate dehydrogenase level of 500 IU/L worked well for estimating the prognosis. We recommend AHSCT at first complete remission for relapsed cases, and it should also be taken into consideration for patients with high prognostic scores at diagnosis. PMID:27094103

  13. Advances in bone marrow stem cell therapy for retinal dysfunction.

    PubMed

    Park, Susanna S; Moisseiev, Elad; Bauer, Gerhard; Anderson, Johnathon D; Grant, Maria B; Zam, Azhar; Zawadzki, Robert J; Werner, John S; Nolta, Jan A

    2017-01-01

    The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34(+) cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34(+) cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy.

  14. Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry.

    PubMed

    Freytes, César O; Loberiza, Fausto R; Rizzo, J Douglas; Bashey, Asad; Bredeson, Christopher N; Cairo, Mitchell S; Gale, Robert Peter; Horowitz, Mary M; Klumpp, Thomas R; Martino, Rodrigo; McCarthy, Philip L; Molina, Arturo; Pavlovsky, Santiago; Pecora, Andrew L; Serna, Derek S; Tsai, Tsuong; Zhang, Mei-Jie; Vose, Julie M; Lazarus, Hillard M; van Besien, Koen

    2004-12-01

    Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly used in patients with lymphoma who experience disease relapse after autologous hematopoietic stem cell transplantation (auto-HSCT) because the allograft is tumor free and may induce a graft-versus-tumor effect. We analyzed 114 patients treated with this approach from 1990 to 1999 to assess disease progression, progression-free survival (PFS), and overall survival (OS). Cumulative incidence of disease progression at 3 years was 52%, whereas treatment-related mortality was 22%, lower than previously reported. Three-year probabilities of OS and PFS were 33% and 25%, respectively. With prolonged follow-up, however, nearly all patients experienced disease progression, and 5-year probabilities were 24% and 5%, respectively. Complete remission at the time of allo-HSCT and use of total body irradiation (TBI) in patients with non-Hodgkin lymphoma (NHL) were associated with lower rates of disease progression and higher rates of OS. In summary, allo-HSCT is feasible for patients with lymphoma who have relapses after auto-HSCT and can result in prolonged survival for some, but it is usually not curative. Most likely to benefit are patients who have HLA-matched sibling donors, are in remission, and have good performance status.

  15. B- and T-lymphocyte number and function in HIV+/HIV− lymphoma patients treated with high-dose chemotherapy and autologous bone marrow transplantation

    PubMed Central

    Bertoli, Diego; Re, Alessandro; Chiarini, Marco; Sottini, Alessandra; Serana, Federico; Giustini, Viviana; Roccaro, Aldo M.; Cattaneo, Chiara; Caimi, Luigi; Rossi, Giuseppe; Imberti, Luisa

    2016-01-01

    Combination of anti-retroviral therapy, high-dose chemotherapy (HCT) and autologous stem cell transplantation (ASCT) has led to an improved survival of HIV+ non-Hodgkin lymphoma (NHL) patients. We compared T- and B-cell subset recovery and related capability to respond to in-vitro stimulation, as well as T-cell repertoire modifications of HIV+ and HIV− NHL patients undergoing HCT and ASCT as first-line consolidation or salvage treatment, using sequential blood samples obtained before and at 3, 6, 12 and 24 months after ASCT. B lymphocyte recovery occurred earlier, reaching higher levels in HIV+ patients as compared to HIV− patients and healthy controls; in particular, immature and naïve B cells were significantly higher in HIV+ patients who had received rituximab in the pre-ASCT period. These lymphocytes equally responded to in-vitro stimulation. Newly produced T cells similarly increased in HIV+ and HIV− NHL patients, but their levels remained constantly lower than in healthy controls. T lymphocytes showed a reduced proliferative capacity, but their repertoire was reassorted by the treatment. The functional and numeric B-cell recovery and the qualitative modifications of T-cell receptor repertoire may explain, at least in part, the success of this aggressive therapeutic approach in HIV+ patients. PMID:27905485

  16. Progenitor Cell Therapy to Treat Acute Myocardial Infarction: The Promise of High-Dose Autologous CD34+ Bone Marrow Mononuclear Cells

    PubMed Central

    Poole, Joseph C.; Quyyumi, Arshed A.

    2013-01-01

    ST elevation myocardial infarction (STEMI) is associated with an increased risk for congestive heart failure and long-term mortality despite the widespread use of thrombolysis and catheter-based revascularization. The need for improved post-STEMI therapies has led to a surge of novel therapeutics, especially regenerative approaches using autologous mononuclear cells. Indeed, the past decade has been marked by a number of human trials studying the safety and efficacy of progenitor cell delivery in the post-STEMI setting. While a variety of cell types and delivery techniques have been utilized, directed therapy to the infarct-related artery has been the most widely used approach. From over 1300 subjects randomized in these studies, there is sufficient evidence to conclude that cell therapy after STEMI is uniformly safe, while the efficacy of this intervention for improving outcomes is less clear. Recent meta-analyses have highlighted the importance of both timing of cell delivery, as well as the type, quantity, and mobility of delivered cells as determinants of response. Here, we show the case in which higher doses of CD34+ cells, which are more potent in terms of their migratory capacity, offer the best hope for preserving cardiac function following STEMI. PMID:23737803

  17. Bilateral maxillary sinus floor augmentation with tissue-engineered autologous osteoblasts and demineralized freeze-dried bone

    PubMed Central

    Deshmukh, Aashish; Kalra, Rinku; Chhadva, Shruti; Shetye, Angad

    2015-01-01

    The pneumatization of the maxillary sinus often results in a lack of sufficient alveolar bone for implant placement. In the last decades, maxillary sinus lift has become a very popular procedure with predictable results. Sinus floor augmentation procedures are generally carried out using autologous bone grafts, bone substitutes, or composites of bone and bone substitutes. However, the inherent limitations associated with each of these, have directed the attention of investigators to new technologies like bone tissue engineering. Bone marrow stromal cells have been regarded as multi-potent cells residing in bone marrow. These cells can be harvested from a person, multiplied outside his body using bioengineering principles and technologies and later introduced into a tissue defect. We present a case where tissue-engineered autologous osteoblasts were used along with demineralized freeze-dried bone for sinus floor augmentation. PMID:26097364

  18. Bone Marrow Matters

    ERIC Educational Resources Information Center

    Dunne, Mark; Maklad, Rania; Heaney, Emma

    2014-01-01

    As a final-year student teacher specialising in primary science, Emma Heaney faced the challenge of having to plan, organise, and conduct a small-scale, classroom-based research project. She had to teach about bones in the final block practice session and thought it would be a good idea to bring in some biological specimens obtained from the local…

  19. The Anatomy of Caprine Female Urethra and Characteristics of Muscle and Bone Marrow Derived Caprine Cells for Autologous Cell Therapy Testing.

    PubMed

    Burdzinska, Anna; Dybowski, Bartosz; Zarychta-Wisniewska, Weronika; Kulesza, Agnieszka; Zagozdzon, Radoslaw; Gajewski, Zdzislaw; Paczek, Leszek

    2017-03-01

    Cell therapy is emerging as an alternative treatment of stress urinary incontinence. However, many aspects of the procedure require further optimization. A large animal model is needed to reliably test cell delivery methods. In this study, we aim to determine suitability of the goat as an experimental animal for testing intraurethral autologous cell transplantation in terms of urethral anatomy and cell culture parameters. The experiments were performed in 12 mature/aged female goats. Isolated caprine muscle derived cells (MDC) were myogenic in vitro and mesenchymal stem cells (MSC) population was able to differentiate into adipo-, osteo- and chondrogenic lineages. The median yield of cells after 3 weeks of culture amounted 47 × 10(6) for MDC and 37 × 10(6) for MSC. Urethral pressure profile measurements revealed the mean functional urethral length of 3.75 ± 0.7 cm. The mean maximal urethral closure pressure amounted 63.5 ± 5.9 cmH2 O and the mean functional area was 123.3 ± 19.4 cm*cmH2 O. The omega- shaped striated urethral sphincter was well developed in the middle and distal third of the urethra and its mean thickness on cross section was 2.3 mm. In the proximal part of the urethra only loosely arranged smooth muscle fibers were identified. To conclude, presented data demonstrate that caprine MDC and MSC can be expanded in vitro in a repeatable manner even when mature or aged animals are cell donors. Results suggest that female caprine urethra has similar parameters to those reported in human and therefore the goat can be an appropriate experimental animal for testing intraurethral cell transplantation. Anat Rec, 00:000-000, 2016. © 2016 Wiley Periodicals, Inc. Anat Rec, 300:577-588, 2017. © 2016 Wiley Periodicals, Inc.

  20. Osteogenic activity of bone marrow-derived mesenchymal stem cells (BMSCs) seeded on irradiated allogenic bone.

    PubMed

    Tohma, Yasuaki; Dohi, Yoshiko; Ohgushi, Hajime; Tadokoro, Mika; Akahane, Manabu; Tanaka, Yasuhito

    2012-02-01

    Allogenic bone grafting, a technique used in orthopaedic surgery, has several problems, including low osteogenic activity. To overcome the problem, this study aimed to determine whether in vivo osteogenesis could be enhanced using allogenic irradiated bone grafts after seeding with autologous bone marrow-derived mesenchymal stem cells (BMSCs). The allogenic bone cylinders were extracted from ACI rats and sterilized by irradiation. Donor BMSCs were obtained from fresh Fischer 344 (F344) rat bone marrow by cell culture. The allogenic bone with or without BMSCs were transplanted subcutaneously into syngeneic F344 rats. At 4 weeks after transplantation, high alkaline phosphatase (ALP) activity, bone-specific osteocalcin mRNA expression and newly formed bone were detected in the allogenic bone with BMSCs. The origin of the newly formed bone was derived from cultured donor BMSCs. However, none of these identifiers of osteogenesis were detected in either the fresh or the irradiated allogenic bone without BMSCs. These results indicate the availability of autologous BMSCs to heighten the osteogenic response of allogenic bone. Our present tissue-engineering method might contribute to a wide variety of allogenic bone grafting techniques in clinical settings.

  1. Primary bone marrow oedema syndromes.

    PubMed

    Patel, Sanjeev

    2014-05-01

    MRI scanning in patients with rheumatological conditions often shows bone marrow oedema, which can be secondary to inflammatory, degenerative, infective or malignant conditions but can also be primary. The latter condition is of uncertain aetiology and it is also uncertain whether it represents a stage in the progression to osteonecrosis in some patients. Patients with primary bone marrow oedema usually have lower limb pain, commonly the hip, knee, ankle or feet. The diagnosis is one of exclusion with the presence of typical MRI findings. Treatment is usually conservative and includes analgesics and staying off the affected limb. The natural history is that of gradual resolution of symptoms over a number of months. Evidence for medical treatment is limited, but open-label studies suggest bisphosphonates may help in the resolution of pain and improve radiological findings. Surgical decompression is usually used as a last resort.

  2. Elimination of clonogenic tumor cells from HL-60, Daudi, and U-937 cell lines by laser photoradiation therapy: implications for autologous bone marrow purging

    SciTech Connect

    Gulliya, K.S.; Pervaiz, S.

    1989-03-01

    Laser photoradiation therapy was tested in an in vitro model for its efficacy in the elimination of non-Hodgkin's lymphoma cells. Results show that at 31.2 J/cm2 of laser light in the presence of 20 micrograms/mL of merocyanine 540 (MC540) there was greater than 5 log reduction in Burkitt's lymphoma (Daudi) cells. Similar tumor cell kill was obtained for leukemia (HL-60) cells at a laser light dose of 93.6 J/cm2. However, to obtain the same efficiency of killing for histiocytic lymphoma (U-937) cells, a higher dose of MC540 (25 micrograms/mL) was required. Clonogenic tumor stem cell colony formation was reduced by greater than 5 logs after laser photoradiation therapy. Under identical conditions for each cell line the percent survival for granulocyte-macrophage colony-forming units (CFU-GM, 45.9%, 40%, 17.5%), granulocyte/erythroid/macrophage/megakaryocyte (GEMM, 40.1%, 20.1%, 11.5%), colony-forming units (CFU-C, 16.2%, 9.1%, 1.8%), and erythroid burst-forming units (BFU-E, 33.4%, 17.8%, 3.9%) was significantly higher than the tumor cells. Mixing of gamma ray-irradiated normal marrow cells with tumor cells (1:1 and 10:1 ratio) did not interfere with the elimination of tumor cells. The effect of highly purified recombinant interferon alpha (rIFN) on laser photoradiation therapy of tumor cells was also investigated. In the presence of rIFN (30 to 3,000 U/mL), the viability of leukemic cells was observed to increase from 0% to 1.5% with a concurrent decrease in membrane polarization, suggesting an increase in fluidity of cell membrane in response to rIFN. However, at higher doses of rIFN (6,000 to 12,000 U/mL) this phenomenon was not observed. The viability of lymphoma cells remained unaffected at all doses of rIFN tested.

  3. An Enzymatic Method to Rescue Mesenchymal Stem Cells from Clotted Bone Marrow Samples

    PubMed Central

    Malonzo, Cherry; Poetzel, Tobias; Baur, Martin; Steffen, Frank; Stoyanov, Jivko

    2015-01-01

    Mesenchymal stem cells (MSCs) - usually obtained from bone marrow - often require expansion culture. Our protocol uses clinical grade urokinase to degrade clots in the bone marrow and release MSCs for further use. This protocol provides a rapid and inexpensive alternative to bone marrow resampling. Bone marrow is a major source of MSCs, which are interesting for tissue engineering and autologous stem cell therapies. Upon withdrawal bone marrow may clot, as it comprises all of the hematopoietic system. The resulting clots contain also MSCs that are lost for expansion culture or direct stem cell therapy. We experienced that 74% of canine bone marrow samples contained clots and yielded less than half of the stem cell number expected from unclotted samples. Thus, we developed a protocol for enzymatic digestion of those clots to avoid labor-intense and costly bone marrow resampling. Urokinase - a clinically approved and readily available thrombolytic drug – clears away the bone marrow clots almost completely. As a consequence, treated bone marrow aspirates yield similar numbers of MSCs as unclotted samples. Also, after urokinase treatment the cells kept their metabolic activity and the ability to differentiate into chondrogenic, osteogenic and adipogenic lineages. Our protocol salvages clotted blood and bone marrow samples without affecting the quality of the cells. This obsoletes resampling, considerably reduces sampling costs and enables the use of clotted samples for research or therapy. PMID:25938767

  4. Induction of allogeneic unresponsiveness by supralethal irradiation and bone marrow reconstitution. [Dogs

    SciTech Connect

    Rapaport, F.T.; Bachvaroff, R.J.; Akiyama, N.; Sato, T.

    1980-09-01

    Supralethally irradiated dogs were reconstituted wth their own stored bone marrow and were challenged at various time intervals with a kidney allograft. The data suggest that transplanted bone marrow cells may participate directly in the events leading to allogenic unresponsiveness. The time interval between marrow cell replacement and kidney allotransplantation required for optimal results suggest that at least one cycle of cell turnover by the replaced stem cells is needed in order to produce unresponsiveness. Host irradiation and reconstitution with stored autologous marrow may be useful in the treatment of certain forms of cancer.

  5. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice

    SciTech Connect

    Colnot, C. . E-mail: colnotc@orthosurg.ucsf.edu; Huang, S.; Helms, J.

    2006-11-24

    The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis.

  6. Inherited Bone Marrow Failure Syndromes (IBMFS)

    Cancer.gov

    The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

  7. Androgen, Estrogen and the Bone Marrow Microenvironment

    DTIC Science & Technology

    2009-12-01

    SUPPLEMENTARY NOTES 14. ABSTRACT We have accomplished the following: 1) Characterized androgen responsive genes in mouse bone marrow (BM) via...castration (androgen ablation) and estrogen stimulation. 2) Measurements of testosterone, dihydrotestosterone and of genes that regulate the local... gene expression in the bone marrow. In males, the main source of estrogen is through conversion of androgen by aromatase. We postulate that gene

  8. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects.

    PubMed

    Wang, Yang; Li, Zheng-Wei; Luo, Min; Li, Ya-Jun; Zhang, Ke-Qiang

    2015-06-01

    The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was

  9. Bone marrow examination in pancytopenia.

    PubMed

    Rangaswamy, M; Prabhu; Nandini, N M; Manjunath, G V

    2012-08-01

    Pancytopenia is defined by reduction of all the three formed elements of blood below the normal reference. It may be a manifestation of a wide variety of disorders, which primarily or secondarily affect the bone marrow. Haematological investigation forms the bedrock in the management of patients with pancytopenia and therefore needs detailed study. The total number of cases studied were 100 over a period of two years in the department of pathology, JSS Hospital, Mysore. Megaloblastic anaemia (33%) was the commonest cause of pancytopenia. Other causes were nutritional anaemia (16%), aplastic anaemia (14%), hypersplenism (10%), sepsis (9%) and leukaemia (5%). Less common causes were alcoholic liver disease, haemolytic anaemia, HIV, dengue, systemic lupus erythematosus, viral hepatitis, disseminated TB and multiple myeloma. Most of the patients were in the age group of 11-30 years with a male:female ratio of 1.6:1.Generalised weakness and fatigue (88%) were the commonest presenting complaints. Haemoglobin level varied from 1-10 g/dl with majorIty (70%) of them in the range of 5.1-10 g/dI. TLC was in the range of 500-4000 cells/cmm. Most (34%) of them had 3100-4000 cells/cmm. Platelet count was in the range of 4000-1,40,000 cells/cmm. Reticulocyte count varied from 0.1%-15% with majority (82%) of them ranging from 0.1%-2%. The bone marrow cellularity was hypocellular in 14%, hypercellular in 75%, and normocellular in 11% of the patients. Pancytopenia is a relatively common entity with inadequate attention in Indian subcontinent. A comprehensive clinical and haematological study of patients with pancytopenia will usually help in the identification of the underlying cause. However in view of wide array of aetiologies, pancytopenia continues to be a diagnostic challenge for haematologists.

  10. [In vitro culture of human autologous osteoblast cells on natural bone mineral].

    PubMed

    Behrens, P; Wolf, E; Bruns, J

    2000-02-01

    Different methods are available for the treatment of osseous defects. In recent years the use of autologous bone was established as the golden standard. However, significant disadvantages are limited availability of the bone graft and its harvest implies additional morbidity for the patient. Alternatives to the use of autologous bone, as allogeneic bone from bone banks or biomaterials like hydroxyapatite are therefore of special interest. However, the currently available methods have severe disadvantages; allogenic bone carries a high risk of transmitting infectious diseases, most biomaterials show an unsatisfying osseous integration as well as prolonged healing with disability for the patient. Therefore, the aim has to be the development of a biomaterial that is as close as possible to human bone. In this in vitro study the natural bone mineral Bio-Oss/Orthos was used as a matrix for human osteoblast-like cells isolated from bone marrow of healthy patients. Even after three months the cell showed typical osteblast-like behaviour. Histologic evaluation demonstrated the ability of Bio-Oss/Orthos to guide cell growth within its matrix structure and therefore mimics in vivo situation of the healthy bone. The results show that culturing human osteoblast-like cells under standardised conditions is possible and that the combination of human osteoblast-like cell with an appropriate matrix may have the potential for a new treatment option of osseous defects.

  11. Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation

    SciTech Connect

    Vriesendorp, H.M.; Halliwell, R.E.; Johnson, P.M.; Fey, T.A.; McDonough, C.M.

    1985-06-01

    The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated.

  12. Megakaryocytes, malignancy and bone marrow vascular niches.

    PubMed

    Psaila, B; Lyden, D; Roberts, I

    2012-02-01

    Dynamic interactions between hematopoietic cells and their specialized bone marrow microenvironments, namely the vascular and osteoblastic 'niches', regulate hematopoiesis. The vascular niche is conducive for thrombopoiesis and megakaryocytes may, in turn, regulate the vascular niche, especially in supporting vascular and hematopoietic regeneration following irradiation or chemotherapy. A role for platelets in tumor growth and metastasis is well established and, more recently, the vascular niche has also been implicated as an area for preferential homing and engraftment of malignant cells. This article aims to provide an overview of the dynamic interactions between cellular and molecular components of the bone marrow vascular niche and the potential role of megakaryocytes in bone marrow malignancy.

  13. [Increased efficacy of allogenic bone marrow transplantation].

    PubMed

    Fedotenkov, A G; Danilova, L A; Ignasheva, L P

    1982-08-01

    Experiments made in vivo and vitro have demonstrated that conservation of allogeneic hemopoietic tissue with glycerin brings about a decrease in transplatation, homologous activity of T lymphocytes. Allogeneic bone marrow conserved with glycerin compares very favourably with freshly prepared allogeneic bone marrow since the transplant-versus-host reaction is attenuated under the effect of glycerin. Moreover, it shows a higher proliferative activity. The glycerin-induced reduction of the inactivating effect of lymphocytes against non-syngeneic colony-forming units enables the conserved bone marrow to be transplanted from several donors.

  14. [Changes in the bone marrow in cancer patients. 61 bone marrow biopsies].

    PubMed

    Marsan, C; Henon, P; Cywiner-Golenzer, C; Zitouna, M M; Girardi, P

    1976-01-01

    The authors studied 61 bone marrow biopsies carried out in cancerous patients, presumably suffering from a bone metastasis and before any treatment. They feel that quantitative and qualitative changes in the bone marrow may be considered to be an indirect diagnostic indication of metastatic spread.

  15. Bone Marrow Stress Decreases Osteogenic Progenitors.

    PubMed

    Ng, Adeline H; Baht, Gurpreet S; Alman, Benjamin A; Grynpas, Marc D

    2015-11-01

    Age-related bone loss may be a result of declining levels of stem cells in the bone marrow. Using the Col2.3Δtk (DTK) transgenic mouse, osteoblast depletion was used as a source of marrow stress in order to investigate the effects of aging on osteogenic progenitors which reside in the marrow space. Five-month-old DTK mice were treated with one or two cycles of ganciclovir to conditionally ablate differentiated osteoblasts, whereas controls were saline-treated. Treatment cycles were two weeks in length followed by four weeks of recovery. All animals were sacrificed at 8 months of age; bone marrow stromal cells (BMSCs) were harvested for cell culture and whole bones were excised for bone quality assessment. Colony-forming unit (CFU) assays were conducted to investigate the osteogenic potential of BMSC in vitro, and RNA was extracted to assess the expression of osteoblastic genes. Bone quality assessments included bone histomorphometry, TRAP staining, microcomputed tomography, and biomechanical testing. Osteoblast depletion decreased CFU-F (fibroblast), CFU-ALP (alkaline phosphatase), and CFU-VK (von Kossa) counts and BMSC osteogenic capacity in cell culture. Ex vivo, there were no differences in bone mineral density of vertebrae or femurs between treatment groups. Histology showed a decrease in bone volume and bone connectivity with repeated osteoblast depletion; however, this was accompanied by an increase in bone formation rate. There were no notable differences in osteoclast parameters or observed bone marrow adiposity. We have developed a model that uses bone marrow stress to mimic age-related decrease in osteogenic progenitors. Our data suggest that the number of healthy BMSCs and their osteogenic potential decline with repeated osteoblast depletion. However, activity of the remaining osteoblasts increases to compensate for this loss in progenitor osteogenic potential.

  16. Bone marrow transplant – children - discharge

    MedlinePlus

    Transplant - bone marrow - children - discharge; Stem cell transplant - children - discharge; Hematopoietic stem cell transplant -children - discharge; Reduced intensity, non-myeloablative transplant - children - discharge; Mini transplant - children - discharge; Allogenic ...

  17. Bone marrow lesions: A systematic diagnostic approach

    PubMed Central

    Grande, Filippo Del; Farahani, Sahar J; Carrino, John A; Chhabra, Avneesh

    2014-01-01

    Bone marrow lesions on magnetic resonance (MR) imaging are common and may be seen with various pathologies. The authors outline a systematic diagnostic approach with proposed categorization of various etiologies of bone marrow lesions. Utilization of typical imaging features on conventional MR imaging techniques and other problem-solving techniques, such as chemical shift imaging and diffusion-weighted imaging (DWI), to achieve accurate final diagnosis has been highlighted. PMID:25114392

  18. Redox Regulation in Bone Marrow Failure

    DTIC Science & Technology

    2012-06-01

    aplastic anemia patients with a p38 MAPK inhibitor can restore defective hematopoietic activity, suggesting the critical role of p38 in bone marrow...hematopoietic stem cells, and eventually leading to bone marrow failure [7, 8] [9] [10]. On the other hand, treating aplastic anemia patients with a p38...in aplastic anemia . J Immunol, 2002. 168(12): p. 5984-8. 12. Ikebuchi, K., et al., Interleukin 6 enhancement of interleukin 3-dependent

  19. 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

  20. Late renal dysfunction in adult survivors of bone marrow transplantation

    SciTech Connect

    Lawton, C.A.; Cohen, E.P.; Barber-Derus, S.W.; Murray, K.J.; Ash, R.C.; Casper, J.T.; Moulder, J.E. )

    1991-06-01

    Until recently long-term renal toxicity has not been considered a major late complication of bone marrow transplantation (BMT). Late renal dysfunction has been described in a pediatric population status post-BMT which was attributable to the radiation in the preparatory regimen. A thorough review of adults with this type of late renal dysfunction has not previously been described. Fourteen of 103 evaluable adult patients undergoing allogeneic (96) or autologous (7) bone marrow transplantation, predominantly for leukemia and lymphomas, at the Medical College of Wisconsin (Milwaukee, WI) have had a syndrome of renal insufficiency characterized by increased serum creatinine, decreased glomerular filtration rate, anemia, and hypertension. This syndrome developed at a median of 9 months (range, 4.5 to 26 months) posttransplantation in the absence of specific identifiable causes. The cumulative probability of having this renal dysfunction is 20% at 1 year. Renal biopsies performed on seven of these cases showed the endothelium widely separated from the basement membrane, extreme thickening of the glomerular basement membrane, and microthrombi. Previous chemotherapy, antibiotics, and antifungals as well as cyclosporin may add to and possibly potentiate a primary chemoradiation marrow transplant renal injury, but this clinical syndrome is most analogous to clinical and experimental models of radiation nephritis. This late marrow transplant-associated nephritis should be recognized as a potentially limiting factor in the use of some intensive chemoradiation conditioning regimens used for BMT. Some selective attenuation of the radiation to the kidneys may decrease the incidence of this renal dysfunction.

  1. Bone-like nodules formed by human bone marrow stromal cells: comparative study and characterization.

    PubMed

    Schecroun, N; Delloye, C h

    2003-03-01

    Autologous bone marrow stromal cells have been proposed as an adjuvant in the treatment of bone nonunion. This cell therapy would require the establishment of culture conditions that permit the rapid expansion of these cells ex vivo while retaining their potential for further differentiation. Our aim was to achieve a full differentiation process using human bone marrow aspirates. We first analyzed the effects of mineralization medium (with ascorbic acid and phosphate) and dexamethasone (dex) during the primary culture of human bone marrow stromal (HBMS) cells on the proliferation/differentiation behavior of first-passage cells. The most appropriate schedule was then selected to further characterize this differentiation model. We showed that primary culture of HBMS cells in proliferation medium (DMEM supplemented with 10% fetal calf serum), with a 48-h treatment by mineralization medium and dex resulted in a better osteoblastic differentiation of first-passage cells than primary culture carried out in mineralization medium with or without dex. We showed that culture of HBMS cells under these conditions (primary culture in proliferation medium, followed by subculture in mineralization medium) led to the formation of specifically mineralized bone-like nodules similar to the ones observed with rat bone marrow stromal cells. Our nodules exhibited three distinct cell types, reproducing in vitro a tissue-like structure. This treatment demonstrated an optimal proliferation and expression of osteoblastic markers such as alkaline phosphatase, osteocalcin, and type I collagen. The primary culture allowed the multiplication of the number of adherent progenitor cells at the initial time of plating by a mean factor of 44,000, which was found to be negatively correlated with age. Thus, this differentiation model could provide a new tool to elaborate an autologous cell therapy designed to enhance osteogenesis.

  2. The pathology of bone marrow failure.

    PubMed

    Leguit, Roos J; van den Tweel, Jan G

    2010-11-01

    An important indication for bone marrow investigation is the presence of bone marrow failure, which manifests itself as (pan)cytopenia. The causes of cytopenia are varied and differ considerably between childhood and adulthood. In the paediatric age group inherited bone marrow failure syndromes are important causes of bone marrow failure, but they play only a minor role in later life. This review gives a comprehensive overview of bone marrow failure disorders in children and adults. We classified the causes of bone marrow failure according to the main presenting haematological abnormality, i.e. anaemia, neutropenia, thrombocytopenia or pancytopenia. The following red cell disorders are discussed: red cell aplasia, sideroblastic anaemia, congenital dyserythropoietic anaemia, haemolytic anaemia, paroxysmal nocturnal haemoglobinuria, iron deficiency anaemia, anaemia of chronic disease and megaloblastic anaemia. The neutropenias occur in the context of Shwachman-Diamond syndrome (SDS), severe congenital neutropenia, cyclic neutropenia, immune-related neutropenia and non-immune neutropenia. In addition, the following causes of thrombocytopenia are discussed: congenital amegakaryocytic thrombocytopenia, thrombocytopenia with absent radii, immune-related thrombocytopenia and non-immune thrombocytopenia. Finally, we pay attention to the following pancytopenic disorders: Fanconi anaemia, dyskeratosis congenita, aplastic anaemia, myelodysplastic syndromes and human immunodeficiency virus (HIV) infection.

  3. Autologous Bone Graft in Foot and Ankle Surgery.

    PubMed

    Miller, Christopher P; Chiodo, Christopher P

    2016-12-01

    Bone graft is a common adjunct procedure in orthopedic surgery used for fusions, fracture repair, and the reconstruction of skeletal defects in the foot and ankle. Autologous graft, or autograft, involves the transport of bone from a donor site to another location in the same patient. It is considered by many to be the gold standard of bone grafting, as it is provides all biologic factors required for functional graft. Further, autograft is 100% histocompatible with no risk of disease transmission.

  4. Gene therapy for monogenic disorders of the bone marrow.

    PubMed

    Ghosh, Sujal; Thrasher, Adrian J; Gaspar, H Bobby

    2015-06-05

    Ex-vivo gene transfer of autologous haematopoietic stem cells in patients with monogenic diseases of the bone marrow has emerged as a new therapeutic approach, mainly in patients lacking a suitable donor for transplant. The encouraging results of initial clinical trials of gene therapy for primary immunodeficiencies were tempered by the occurrence of genotoxicity in a number of patients. Over the last decade, safer viral vectors have been developed to overcome the risk of insertional mutagenesis and have led to impressive clinical outcomes with considerably improved safety. We review the efforts in specific immunodeficiencies including adenosine deaminase deficiency, X-linked severe combined immunodeficiency, chronic granulomatous disease and Wiskott Aldrich syndrome. Major recent progress has also been made in haemoglobinopathies, such as beta-thalassaemia, sickle cell disease and Fanconi anaemia, and also specific lysosomal storage diseases, which, although not strictly bone marrow specific conditions, have been effectively treated by bone marrow-based treatment. The success of these recent studies and the advent of new technologies, such as gene editing, suggest that gene therapy could become a more generally applied treatment modality for a number of haematopoietic disorders.

  5. The Challenge and the Promise of Bone Marrow Cells for Human Cartilage Repair.

    PubMed

    Chu, Constance R

    2015-04-01

    The cartilage repair potential of bone marrow-derived stem cells has been well described. Harnessing this potential for human articular cartilage repair remains challenging. Accessing bone marrow repair cells through marrow stimulation techniques such as microfracture is readily achieved with generally good but inconsistent results. Animal and human studies show feasibility for ex vivo processing of bone marrow to isolate, concentrate, and culture mesenchymal stem cells. Nevertheless, it has been difficult to show consistent and clinically meaningful improvement using bone marrow cell preparations above what has been achieved with microfracture. Consequently, microfracture continues to be the simplest and most commonly used method to enhance repair of focal articular cartilage defects. Emerging preclinical work in the equine model suggests a role for enhancing marrow-stimulation techniques through the use of natural scaffolds such as autologous platelet enriched fibrin as well as optimization of joint biology through localized gene therapy to support cartilage repair. In contrast to joint replacement where inert materials of known mechanical properties are used, host biology determines the relative success, failure, and durability of cartilage repair. As such, development of personalized strategies to improve the quality and durability of bone marrow cell-based articular cartilage repair represent exciting new areas of inquiry. Continued advances in stem cell biology, scaffold technologies, and methods to delineate and enhance host biology, both systemically and within the joint, hold promise for harnessing the full power of bone marrow cells to facilitate cartilage repair and regeneration.

  6. [Bone and Stem Cells. Intravital imaging of bone marrow microenvironment].

    PubMed

    Mizuno, Hiroki; Kikuta, Junichi; Ishii, Masaru

    2014-04-01

    Various kinds of cell types, such as osteoclasts, osteoblasts, hematopoietic cells, and mesenchymal cells, have been reported to exist in the bone marrow and communicate with each other. Although there have been many previous studies about bone marrow microenvironment, most of them were analyzed by conventional methods such as histological analysis and flow cytometry. These methods could not observe the dynamic cell movement in living bone marrow. Recently rapid development of fluorescent imaging techniques enables us to understand the cellular dynamics in vivo . That's why we have originally established an advanced imaging system for visualizing living bone tissues with intravital two-photon microscopy. Here we show the latest data and the detailed methodology of intravital imaging of bone marrow microenvironment, and also discuss its further application.

  7. Evidence for transdifferentiation of human bone marrow-derived stem cells: recent progress and controversies.

    PubMed

    Tao, Helen; Ma, David D F

    2003-02-01

    Adult bone marrow-derived stem cells have traditionally been known as tissue-specific stem cells capable of producing blood cells. This concept is being challenged by a series of recent discoveries. It has been demonstrated that there are heterogeneous stem cell populations in adult bone marrow compartment. Under appropriate experimental conditions, a certain type of bone marrow stem cells appears to differentiate (or transdifferentiate) into a variety of non-haemopoietic cells of ectodermal, mesodermal and endodermal origins (such as myocytes, neural cells and hepatocytes). The plasticity, that is, the ability to regenerate cells belonging to different organs and tissues of adult (postnatal) stem cells, has raised the therapeutic possibility of using these stem cells for tissue repair and regeneration. Presently, definitive evidence for plasticity or transdifferentiation of bone marrow stem cells is lacking. Despite controversies concerning the plasticity of bone marrow-derived stem cells, early clinical trials are being conducted in patients suffering from myocardial infarct, arthritic and neurological diseases using autologous bone marrow stem cells. This review summarises recent progresses and controversies in transdifferentiation of adult bone marrow-derived stem cells to non-haemopoietic tissues.

  8. THE USE OF PLATELET RICH PLASMA WITH BONE MARROW ASPIRATE IN PUDDU TIBIAL OSTEOTOMY

    PubMed Central

    D’Elia, Caio Oliveira; de Rezende, Márcia Uchoa; Bitar, Alexandre Carneiro; Tatsui, Nelson; Pécora, José Ricardo; Camanho, Gilberto Luis

    2015-01-01

    Objective: The present study was performed in order to evaluate the use of platelet rich plasma associated to bone marrow aspirate, substituting autologous iliac bone graft in medial opening wedge osteotomy (OWHTO). Methods: Twenty-five patients were submitted to tibial opening wedge osteotomy, being divided into two groups. Iliac group: 14 patients submitted to OWHTO, using autologous iliac bone graft to fill the gap. PRP group: 11 patients using platelet rich plasma associated to bone marrow aspirate to fill the gap. We evaluated bleeding (hemoglobin and hematocrit levels) and pain (visual analogic scale-VAS), then we compared the groups regarding these variables. Results: Differences between the groups were not found regarding hemoglobin levels (p=0.820) and hematocrit levels (p=0.323). The groups were not different regarding pain measured with VAS (p=0.538). Conclusion: The use of platelet rich plasma associated to bone marrow aspirate in medial opening wedge osteotomy did not offer advantages over autologous iliac bone graft regarding bleeding and pain. PMID:27077061

  9. [Hematopoietic growth factors in primary and therapy-related bone marrow insufficiency].

    PubMed

    Hansen, B; Hippe, E; Jacobsen, G K; Johnsen, H E

    1992-06-08

    This investigation is retrospective and comprises 20 patients with bone-marrow insufficiency. During the period 1.4.1988-1.3.1991, these patients were treated with erythropoietin (Epo), the granulocyte-macrophage-colony-stimulating factor (GM-CSF) or the granulocyte-colony-stimulating factor (G-CSF). Thirteen patients had primary bone-marrow insufficiency: six had the myelodysplastic syndrome, three had primary myelofibrosis, two aplastic anemia and two myelomatosis. On account of dominating symptoms of anemia, five patients received Epo while eight received GM-CSF as part of an extensive clinical trial of this preparation. Seven patients with relapse of the haematological malignant disease had bone-marrow insufficiency and pancytopenia secondary to intensive chemotherapy/irradiation: four of these patients received GM-CSF and two received G-CSF with the object of increasing bone-marrow regeneration and to render further chemotherapy possible. One patient received GM-CSF with the object of improving bone-marrow function after autologous bone-marrow transplantation. Treatment with Epo for ten months combined with treatment with interferon for six months resulted in normalization of the haemoglobin concentration in one patient with bone-marrow insufficiency on account of primary myelofibrosis. Treatment with Epo for briefer periods in lower doses was without effect in four other patients with primary bone-marrow insufficiency. Treatment with GM-CSF and G-CSF resulted in neutrophil leukocytosis in 12 out of 15 patients (80%) and, in six out of 14 patients (43%), increased marrow cellularity was demonstrated by means of histological examination of the bone-marrow. One patient showed normal haemoglobin levels during treatment with GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Abnormal bone marrow histopathology in paediatric mastocytosis.

    PubMed

    Carter, Melody C; Metcalfe, Dean D; Clark, Alicia S; Wayne, Alan S; Maric, Irina

    2015-03-01

    The diagnostic criteria for paediatric mastocytosis are largely based on adult studies and bone marrow findings are not well described in children. We evaluated use of the World Health Organization (WHO) criteria for the diagnosis of systemic disease in paediatric mastocytosis. In addition, we identified unique clinico-histopathological features within the biopsies. One hundred and thirteen children with paediatric mastocytosis were evaluated at the National Institutes of Health between 1986 and 2013. Complete bone marrow evaluations were performed in 50 cases. Seven children had repeat procedures. Bone marrows were analysed by histopathology, flow cytometry and for KIT D816V. Bone marrow biopsies displayed mild atypical haematopoietic maturation, increased haematogones and hypocellularity in a sub-set of patients with urticaria pigmentosa, diffuse cutaneous mastocytosis and indolent systemic mastocytosis. Hypocellularity was most pronounced in those with urticaria pigmentosa. Haematogones were highest, on average, in patients with diffuse cutaneous mastocytosis or mastocytomas. There was no evidence of peripheral blood cytopenias, myelodysplastic syndrome, myeloproliferative neoplasm or leukaemia within this cohort. The WHO criteria are applicable for the diagnosis of systemic mastocytosis in paediatrics. Although unsuspected bone marrow findings typically seen in myeloproliferative disorders are frequent in paediatric mastocytosis, patients within this study remained clinically stable without progression to a more aggressive variant.

  11. Radionuclide imaging of bone marrow disorders.

    PubMed

    Agool, Ali; Glaudemans, Andor W J M; Boersma, Hendrikus H; Dierckx, Rudi A J O; Vellenga, Edo; Slart, Riemer H J A

    2011-01-01

    Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-labelled tracers, such as (99m)Tc-nanocolloid, (99m)Tc-sulphur colloid, (111)In-chloride, and radiolabelled white blood cells, have been used in nuclear medicine for several decades. With these techniques three separate compartments can be recognized including the reticuloendothelial system, the erythroid compartment and the myeloid compartment. Recent developments in research and the clinical use of PET tracers have made possible the analysis of additional properties such as cellular metabolism and proliferative activity, using (18)F-FDG and (18)F-FLT. These tracers may lead to better quantification and targeting of different cell systems in the bone marrow. In this review the imaging of different bone marrow targets with radionuclides including PET tracers in various bone marrow diseases are discussed.

  12. Tracking Mouse Bone Marrow Monocytes In Vivo

    PubMed Central

    Hamon, Pauline; Rodero, Mathieu Paul; Combadière, Christophe; Boissonnas, Alexandre

    2015-01-01

    Real time multiphoton imaging provides a great opportunity to study cell trafficking and cell-to-cell interactions in their physiological 3-dimensionnal environment. Biological activities of immune cells mainly rely on their motility capacities. Blood monocytes have short half-life in the bloodstream; they originate in the bone marrow and are constitutively released from it. In inflammatory condition, this process is enhanced, leading to blood monocytosis and subsequent infiltration of the peripheral inflammatory tissues. Identifying the biomechanical events controlling monocyte trafficking from the bone marrow towards the vascular network is an important step to understand monocyte physiopathological relevance. We performed in vivo time-lapse imaging by two-photon microscopy of the skull bone marrow of the Csf1r-Gal4VP16/UAS-ECFP (MacBlue) mouse. The MacBlue mouse expresses the fluorescent reporters enhanced cyan fluorescent protein (ECFP) under the control of a myeloid specific promoter 1, in combination with vascular network labelling. We describe how this approach enables the tracking of individual medullar monocytes in real time to further quantify the migratory behaviour within the bone marrow parenchyma and the vasculature, as well as cell-to-cell interactions. This approach provides novel insights into the biology of the bone marrow monocyte subsets and allows to further address how these cells can be influenced in specific pathological conditions. PMID:25867540

  13. Bone marrow osteoblast vulnerability to chemotherapy.

    PubMed

    Gencheva, Marieta; Hare, Ian; Kurian, Susan; Fortney, Jim; Piktel, Debbie; Wysolmerski, Robert; Gibson, Laura F

    2013-06-01

    Osteoblasts are a major component of the bone marrow microenvironment, which provide support for hematopoietic cell development. Functional disruption of any element of the bone marrow niche, including osteoblasts, can potentially impair hematopoiesis. We have studied the effect of two widely used drugs with different mechanisms of action, etoposide (VP16) and melphalan, on murine osteoblasts at distinct stages of maturation. VP16 and melphalan delayed maturation of preosteoblasts and altered CXCL12 protein levels, a key regulator of hematopoietic cell homing to the bone marrow. Sublethal concentrations of VP16 and melphalan also decreased the levels of several transcripts which contribute to the composition of the extracellular matrix (ECM) including osteopontin (OPN), osteocalcin (OCN), and collagen 1A1 (Col1a1). The impact of chemotherapy on message and protein levels for some targets was not always aligned, suggesting differential responses at the transcription and translation or protein stability levels. As one of the main functions of a mature osteoblast is to synthesize ECM of a defined composition, disruption of the ratio of its components may be one mechanism by which chemotherapy affects the ability of osteoblasts to support hematopoietic recovery coincident with altered marrow architecture. Collectively, these observations suggest that the osteoblast compartment of the marrow hematopoietic niche is vulnerable to functional dysregulation by damage imposed by agents frequently used in clinical settings. Understanding the mechanistic underpinning of chemotherapy-induced changes on the hematopoietic support capacity of the marrow microenvironment may contribute to improved strategies to optimize patient recovery post-transplantation.

  14. Bone marrow cells and myocardial regeneration.

    PubMed

    Wang, Fu-Sheng; Trester, Cathy

    2004-05-01

    Hematopoietic stem cell (HSC) plasticity and its clinical application have been studied profoundly in the past few years. Recent investigations indicate that HSC and other bone marrow stem cells can develop into other tissues. Because of the high morbidity and mortality of myocardial infarction and other heart disorders, myocardial regeneration is a good example of the clinical application of HSC plasticity in regenerative medicine. Preclinical studies in animals suggest that the use of this kind of treatment can reconstruct heart blood vessels, muscle, and function. Some clinical study results have been reported in the past 2 years. In 2003, reports of myocardial regeneration treatment increased significantly. Other studies include observations on the cell surface markers of transplanted cells and treatment efficacy. Some investigations, such as HSC testing, have focused on clinical applications using HSC plasticity and bone marrow transplantation to treat different types of disorders. In this review, we focus on the clinical application of bone marrow cells for myocardial regeneration.

  15. A patient with progressive multiple myeloma treated successfully with arsenic trioxide after allogeneic bone marrow transplantation.

    PubMed

    Gesundheit, B; Shapira, M Y; Ackerstein, A; Resnik, I B; Bitan, M; Or, R

    2007-01-01

    Multiple myeloma (MM) is an incurable progressive disease. Many therapeutic options are available to delay progression, including autologous and allogeneic bone marrow transplantation. At advanced stages, MM is often refractory to treatment. We report a heavily pretreated patient with graft-versus-host disease after bone marrow transplantations, treated at a terminal stage with a modified protocol for arsenic trioxide (ATO). This patient with poor clinical status tolerated the treatment very well. He had a remarkable clinical response and achieved complete remission. The mechanisms of ATO are presented and the potential role of ATO for MM is discussed.

  16. National Marrow Donor Program. HLA Typing for Bone Marrow Transplantation

    DTIC Science & Technology

    2014-11-30

    event. 3. Immunogenetic Studies: Increase understanding of the immunologic factors important in HSC transplantation. 4. Clinical Research... Immunology , and Transplantation DaSH Data Standards Hackathon DC Donor Center National Marrow Donor Program® N00014-13-1-0039 HLA Typing for Bone...Management Strategy ImmPort Immunology Database and Analysis Portal IND Investigational New Drug IND Improvised Nuclear Device IPR Immunobiology Project

  17. Delayed Cranioplasty: Outcomes Using Frozen Autologous Bone Flaps

    PubMed Central

    Hng, Daniel; Bhaskar, Ivan; Khan, Mumtaz; Budgeon, Charley; Damodaran, Omprakash; Knuckey, Neville; Lee, Gabriel

    2014-01-01

    Reconstruction of skull defects following decompressive craniectomy is associated with a high rate of complications. Implantation of autologous cryopreserved bone has been associated with infection rates of up to 33%, resulting in considerable patient morbidity. Predisposing factors for infection and other complications are poorly understood. Patients undergoing cranioplasty between 1999 and 2009 were identified from a prospectively maintained database. Records and imaging were reviewed retrospectively. Demographics, the initial craniectomy and subsequent cranioplasty surgeries, complications, and outcomes were recorded. A total of 187 patients underwent delayed cranioplasty using autologous bone flaps cryopreserved at –30°C following decompressive craniectomy. Indications for craniectomy were trauma (77.0%), stroke (16.0%), subarachnoid hemorrhage (2.67%), tumor (2.14%), and infection (2.14%). There were 64 complications overall (34.2%), the most common being infection (11.2%) and bone resorption (5.35%). After multivariate analysis, intraoperative cerebrospinal fluid (CSF) leak was significantly associated with infection, whereas longer duration of surgery and unilateral site were associated with resorption. Cranioplasty using frozen autologous bone is associated with a high rate of infective complications. Intraoperative CSF leak is a potentially modifiable risk factor. Meticulous dissection during cranioplasty surgery to minimize the chance of breaching the dural or pseudodural plane may reduce the chance of bone flap. PMID:26269726

  18. Human autologous mesenchymal stem cells with extracorporeal shock wave therapy for nonunion of long bones

    PubMed Central

    Zhai, Lei; Ma, Xin-Long; Jiang, Chuan; Zhang, Bo; Liu, Shui-Tao; Xing, Geng-Yan

    2016-01-01

    Background: Currently, the available treatments for long bone nonunion (LBN) are removing of focus of infection, bone marrow transplantation as well as Ilizarov methods etc. Due to a high percentage of failures, the treatments are complex and debated. To develop an effective method for the treatment of LBN, we explored the use of human autologous bone mesenchymal stems cells (hBMSCs) along with extracorporeal shock wave therapy (ESWT). Materials and Methods: Sixty three patients of LBN were subjected to ESWT treatment and were divided into hBMSCs transplantation group (Group A, 32 cases) and simple ESWT treatment group (Group B, 31 cases). Results: The patients were evaluated for 12 months after treatment. In Group A, 14 patients were healed and 13 showed an improvement, with fracture healing rate 84.4%. In Group B, eight patients were healed and 13 showed an improvement, with fracture healing rate 67.7%. The healing rates of the two groups exhibited a significant difference (P < 0.05). There was no significant difference for the callus formation after 3 months treatment (P > 0.05). However, the callus formation in Group A was significantly higher than that in the Group B after treatment for 6, 9, and 12 months (P < 0.05). Conclusion: Autologous bone mesenchymal stems cell transplantation with ESWT can effectively promote the healing of long bone nonunions. PMID:27746499

  19. Repair of segmental bone defects with bone marrow and BMP-2 adenovirus in the rabbit radius

    NASA Astrophysics Data System (ADS)

    Cheng, Lijia; Lu, Xiaofeng; Shi, Yujun; Li, Li; Xue, Jing; Zhang, Li; Xia, Jie; Wang, Yujia; Zhang, Xingdong; Bu, Hong

    2012-12-01

    Bone tissue engineering (BTE) is approached via implantation of autogenous mesenchymal stem cells (MSCs), marrow cells, or platelet-rich plasma, etc. To the contrary, gene therapy combining with the bone marrow (BM) has not been often reported. This study was performed to investigate whether a modified BTE method, that is, the BM and a recombinant human bone morphogenetic protein-2 adenovirus (Ad.hBMP-2) gene administering in hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) ceramics could accelerate the healing of segmental defects in the rabbit radius. In our study, ceramics were immersed in the adenovirus overnight, and half an hour before surgery, autologous BM aspirates were thoroughly mixed with the ceramics; at the same time, a 15-mm radius defect was introduced in the bilateral forelimbs of all animals, after that, this defect was filled with the following: (1) Ad.hBMP-2 + HA/β-TCP + autologous BM (group 1); (2) HA/β-TCP + Ad.hBMP-2 (group 2); (3) HA/β-TCP alone (group 3); (4) an empty defect as a control (group 4). Histological observation and μ-CT analyses were performed on the specimens at weeks 2, 4, 8, and 12, respectively. In group 1, new bone was observed at week 4 and BM appeared at week 12, in groups 2 and 3, new bone was observed at week 8 and it was more mature at week 12, in contrast, the defect was not bridged in group 4 at week 12. The new bone area percentage in group 1 was significantly higher than that in groups 2 and 3. Our study indicated that BM combined with hBMP-2 adenovirus and porous ceramics could significantly increase the amount of newly formed bone. And this modified BTE method thus might have potentials in future clinical application.

  20. Bone marrow-derived lung epithelial cells.

    PubMed

    Krause, Diane S

    2008-08-15

    Bone marrow-derived cells can take on the phenotype of epithelial cells and express epithelial-specific genes in multiple organs. Here, we focus on recent data on the appearance of marrow-derived epithelial cells in the adult lung. These findings have garnered significant skepticism because in most cases marrow-derived epithelial cells are very rare, the marrow cell of origin is not known, the techniques for detection have needed improvement, and there seem to be multiple mechanisms by which this occurs. Recent studies have focused on these concerns. Once these important concerns are addressed, further studies on the function(s) of these cells will need to be performed to determine whether this engraftment has any clinical significance-either beneficial or detrimental.

  1. The diagnostic value of bone marrow iron.

    PubMed

    Wulfhekel, U; Düllmann, J

    1990-01-01

    The light and electronmicroscopic representation of non-haemiron in the bone-marrow provides the unique opportunity of extensively evaluating the iron metabolism. In the bone-marrow, macrophages represent the physiological place of iron storage. The iron in the cytoplasma is stored in them in the form of free ferritin molecules and lysomally as aggregated ferritin and/or haemosiderin in siderosomes. In an equal iron balance and unimpaired internal iron exchange only erythroblasts (sideroblasts) and erythrocytes (siderocytes) of the bone-marrow besides macrophages possess siderosomes. In addition to this physiological or orthotopic iron storage a heterotopic iron storage can be observed under pathological conditions, particularly with iron overloading of the organism, in the endothelial cells of sinusoids and plasma cells. In detail, the patterns of iron storage in the bone-marrow are described in the different stages of iron deficiency, disturbance of iron utilization in chronically inflammatory processes or tumour diseases, condition after intravenous iron administration, transfusion siderosis, hereditary haemochromatosis and sideroblastic anaemia.

  2. What Is a Blood and Marrow Stem Cell Transplant?

    MedlinePlus

    ... and Bone Marrow Transplant Also known as hematopoietic stem cell transplant, hematopoietic cell transplant, autologous transplant, or allogeneic ... or bone marrow transplant replaces abnormal blood-forming stem cells with healthy cells. When the healthy stem cells ...

  3. Rapid autologous marrow recovery and eradication of infectious mononucleosis despite severe immunosuppression following second transplantation for aplastic anemia.

    PubMed

    Rossbach, H C; Hosler, K M; Chamizo, W; Mueller, T; Grana, N H; Lacson, A G; Barbosa, J L

    1999-01-01

    A patient with aplastic anemia failed to respond to immunosuppressive therapy and first marrow transplantation (BMT). Recovery of autologous hematopoiesis was rapid following a second stem cell transplant with a non-myeloablative preparatory regimen. The autologous immune response to infectious mononucleosis (IM) 4 weeks post-transplant was normal despite recent and ongoing severe immunosuppression.

  4. Platelet leukocyte gel facilitates bone substitute growth and autologous bone growth in a goat model.

    PubMed

    Everts, Peter A M; Delawi, Diyar; Mahoney, Christine Brown; van Erp, Albert; Overdevest, Eddy P; van Zundert, André; Knape, Johannes T A; Dhert, Wouter J A

    2010-02-01

    The aim of this study is to evaluate multiple conditions on the formation of bone growth in a goat model. We prepared from a unit of whole blood, platelet-leukocyte gel (PLG) to stimulate bone formation, based on the release of platelet growth factors. Two 3-compartment cages containing autologous bone, calcium phosphate, and trabecular metal were implanted onto goat spinal transverse processes. One cage was treated with PLG, prepared according to a standardized protocol. An untreated cage served as a control. To monitor bone formation overtime, fluorochrome markers were administered at 2, 3, and 5 weeks. Animals were sacrificed at 9 weeks after implantation. Bone growth in these 3-compartments cages was examined by histology and histomorphometry of nondecalcified sections using traditional light and epifluorescent microscopy. Compared to the control samples, bone growth in the PLG-treated autologous bone and calcium phosphate samples was significantly more. Fairly little bone growth was seen in PLG treated or untreated trabecular metal scaffolds. The results obtained from this goat model suggest a potential role for the application of autologous PLG during surgeries in which autologous bone grafts or calcium phosphate scaffolds are used.

  5. MR imaging of therapy-induced changes of bone marrow

    PubMed Central

    Henning, Tobias; Link, Thomas M.

    2006-01-01

    MR imaging of bone marrow infiltration by hematologic malignancies provides non-invasive assays of bone marrow cellularity and vascularity to supplement the information provided by bone marrow biopsies. This article will review the MR imaging findings of bone marrow infiltration by hematologic malignancies with special focus on treatment effects. MR imaging findings of the bone marrow after radiation therapy and chemotherapy will be described. In addition, changes in bone marrow microcirculation and metabolism after anti-angiogenesis treatment will be reviewed. Finally, new specific imaging techniques for the depiction of regulatory events that control blood vessel growth and cell proliferation will be discussed. Future developments are directed to yield comprehensive information about bone marrow structure, function and microenvironment. PMID:17021706

  6. Characterisation of osteophytes as an autologous bone graft source

    PubMed Central

    Ishihara, K.; Akiyama, T.; Akasaki, Y.; Nakashima, Y.

    2017-01-01

    provide evidence of favourable features of osteophytes for bone mineralisation through a direct effect on osteoblasts. The acceleration in metabolic activity of the osteophyte provides justification for future studies evaluating the clinical use of osteophytes as autologous bone grafts. Cite this article: K. Ishihara, K. Okazaki, T. Akiyama, Y. Akasaki, Y. Nakashima. Characterisation of osteophytes as an autologous bone graft source: An experimental study in vivo and in vitro. Bone Joint Res 2017;6:73–81. DOI: 10.1302/2046-3758.62.BJR-2016-0199.R1. PMID:28148490

  7. 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

  8. Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow transplantation.

    PubMed

    Wen, Yanting; Ouyang, Jian; Yang, Rong; Chen, Junhao; Liu, Yong; Zhou, Xiaojun; Burt, Richard K

    2008-09-19

    Autologous hematopoietic stem cell transplantation (HSCT) has recently been performed as a novel strategy to treat patients with new-onset type 1 diabetes (T1D). However, the mechanism of autologous HSCT-induced remission of diabetes remains unknown. In order to help clarify the mechanism of remission-induction following autologous HSCT in patients with T1D, mice treated with multiple low doses of streptozotocin to induce diabetes were used as both donors (n=20) and recipients (n=20). Compared to streptozocin-treated mice not receiving transplantation, syngeneic bone marrow transplantation (syn-BMT) from a streptozocin-treated diabetic donor, if applied during new-onset T1D (day 10 after diabetes onset), can reverse hyperglycemia without relapse (P<0.001), maintain normal blood insulin levels (P<0.001), and preserve islet cell mass. Compared to diabetic mice not undergoing HSCT, syn-BMT, results in restoration of Tregs in spleens (P<0.01), increased Foxp3 mRNA expression (P<0.01) and increased Foxp3 protein expression (P<0.05). This diabetic-remission-inducing effect occurred in mice receiving bone marrow from either streptozocin-treated diabetic or non-diabetic normal donors. We conclude that autologous HSCT remission of diabetes is more than transient immune suppression, and is capable of prolonged remission-induction via regeneration of CD4+CD25+FoxP3+ Tregs.

  9. Immunophenotypic and ultrastructural study in peripheral blood neutrophil granulocytes following bone marrow transplantation.

    PubMed

    Masat, T; Feliu, E; Villamor, N; Castellsagué, J; Ordi, J; Fabregues, M; Rozman, C

    1997-08-01

    Neutrophil studies after bone marrow transplantation (BMT) describe chemotactic and phagocytotic alterations and dyshaemopoiesis. Neutrophil granulocytes (NG) in peripheral blood after BMT were analysed in 28 patients. 14 patients (six receiving GM-CSF) underwent autologous BMT and 14 underwent allogeneic BMT. Immunophenotypic and electron microscopic studies were performed during post-BMT granulopoietic regeneration. Results were compared with NG from 15 healthy bone marrow donors (control group A) and from six patients receiving intensive chemotherapy before autologous BMT (control group B). A significant increase in CD15 and a decrease in 8C7 antigen expression was observed in peripheral blood NG from BMT patients compared with controls A. MPO-7 in NG after BMT did not differ from control group A. Autologous BMT patients showed a lower percentage of NG expressing 13F6, 31D8 and CD16 (Leu 11a) than allogeneic BMT patients, and a significant decrease in 8C7 antigen expression compared with patients receiving intensive chemotherapy. Ultrastructurally, a marked decrease of azurophilic granules was observed in NG from BMT patients compared with control groups A and B. These data indicate that repopulation after BMT was made by phenotypically less mature NG with dysgranulopoietic features. Differences between autologous and allogeneic BMT patients may be partly related to GM-CSF usage. In conclusion, NG present immunophenotypic and ultrastructural changes after BMT which may be involved in abnormal NG response against bacterial infections, although further investigation is needed.

  10. Tracking Intracavernously Injected Adipose-Derived Stem Cells to Bone Marrow

    PubMed Central

    Lin, Guiting; Qiu, Xuefeng; Fandel, Thomas; Banie, Lia; Wang, Guifang; Lue, Tom F.; Lin, Ching-Shwun

    2012-01-01

    Intracavernous (IC) injection of stem cells (SCs) has been shown to improve erectile function in various erectile dysfunction (ED) animal models. However, the tissue distribution of the injected cells remains unknown. In this study we tracked IC injected adipose-derived stem cells (ADSCs) in various tissues. Rat paratesticular fat was processed for ADSC isolation and culture. The animals were then subject to cavernous nerve (CN) crush injury or sham operation, followed by IC injection of one million autologous or allogeneic ADSCs that were labeled with 5-ethynyl-2-deoxyuridine (EdU). Another group of rats received IC injection of EdU-labeled allogeneic penile smooth muscle cells (PSMCs). At 2 and 7 days post-injection, penises and femoral bone marrow were processed for histological analyses. Whole femoral bone marrows were also analyzed for EdU-positive cells by flow cytometry. The results show that ADSCs exited the penis within days of IC injection and migrated preferentially to bone marrow. Allogenicity did not affect ADSC's bone marrow appearance either at 2 or 7 days, while CN injury reduced the number of ADSCs in bone marrow significantly at 7 but not 2 days. The significance of these results in relation to SC therapy for ED is discussed. PMID:21796145

  11. Immune humanization of immunodeficient mice using diagnostic bone marrow aspirates from carcinoma patients.

    PubMed

    Werner-Klein, Melanie; Proske, Judith; Werno, Christian; Schneider, Katharina; Hofmann, Hans-Stefan; Rack, Brigitte; Buchholz, Stefan; Ganzer, Roman; Blana, Andreas; Seelbach-Göbel, Birgit; Nitsche, Ulrich; Männel, Daniela N; Klein, Christoph A

    2014-01-01

    Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs) from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null) (NSG) and HLA-I expressing NSG mice (NSG-HLA-A2/HHD) comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.

  12. Magnetic resonance imaging of bone marrow disease in children

    SciTech Connect

    Cohen, M.D.; Klatte, E.C.; Baehner, R.; Smith, J.A.; Martin-Simmerman, P.; Carr, B.E.; Provisor, A.J.; Weetman, R.M.; Coates, T.; Siddiqui, A.

    1984-06-01

    Seven children underwent magnetic resonance imaging (MRI) of the bone marrow: results showed that it is technically feasible to obtain good MR images of marrow in children. MR has detected abnormality in the bone marrow of a child who had metastatic neuroblastoma. The extent of abnormality in the femur correlated well with findings of a bone marrow isotope scan. In one child who had idiopathic aplastic anemia, diseased marrow could not be distinguished from normal marrow on MR images. MRI identified abnormality of the marrow in osteogenic sarcoma, and demonstrated change in response to chemotherapy. It displayed marrow spread of tumors as well as CT. MRI showed marrow abnormality in four children who had leukemia.

  13. Evaluation of hydroxyapatite and beta-tricalcium phosphate mixed with bone marrow aspirate as a bone graft substitute for posterolateral spinal fusion

    PubMed Central

    Bansal, Sanjay; Chauhan, Vijendra; Sharma, Sansar; Maheshwari, Rajesh; Juyal, Anil; Raghuvanshi, Shailendra

    2009-01-01

    Background: Autologous cancellous bone is the most effective biological graft material. However, harvest of autologous bone is associated with significant morbidity. Since porous hydroxyapatite and beta-tricalcium phosphate are biodegradable materials and can be replaced by bone tissue, but it lacks osteogenic property. We conducted a study to assess their use as a scaffold and combine them with bone marrow aspirate for bone regeneration using its osteogenic property for posterolateral spinal fusion on one side and autologous bone graft on the other side and compare them radiologically in terms of graft incorporation and fusion. Materials and Methods: Thirty patients with unstable dorsal and lumbar spinal injuries who needed posterior stabilization and fusion were evaluated in this prospective study from October 2005 to March 2008. The posterior stabilization was done using pedicle screw and rod assembly, and fusion was done using hydroxyapatite and beta-tricalcium phosphate mixed with bone marrow aspirate as a bone graft substitute over one side of spine and autologous bone graft obtained from iliac crest over other side of spine. The patients were followed up to a minimum of 12 months. Serial radiographs were done at an interval of 3, 6, and 12 months and CT scan was done at one year follow-up. Graft incorporation and fusion were assessed at each follow-up. The study was subjected to statistical analysis using chi-square and kappa test to assess graft incorporation and fusion. Results: At the end of the study, radiological graft incorporation and fusion was evident in all the patients on the bone graft substitute side and in 29 patients on the autologous bone graft side of the spine (P > 0.05). One patient showed lucency and breakage of distal pedicle screw in autologous bone graft side. The interobserver agreement (kappa) had an average of 0.72 for graft incorporation, 0.75 for fusion on radiographs, and 0.88 for the CT scan findings. Conclusion: Hydroxyapatite

  14. Bone Marrow Edema: Chronic Bone Marrow Lesions of the Knee and the Association with Osteoarthritis.

    PubMed

    Collins, Jason A; Beutel, Bryan G; Strauss, Eric; Youm, Thomas; Jazrawi, Laith

    2016-03-01

    Bone marrow edema of the knee occurs secondary to a myriad of causes. The hallmark of a bone marrow lesion (BML) is an area of decreased signal intensity on T1 weighted MRI with a corresponding area of increased signal intensity on a T2 weighted MRI. Recently, chronic bone marrow lesions have been correlated with knee pain and progression of osteoarthritis. These lesions have also been associated with other degenerative conditions such as meniscal tears, cartilage deterioration, subchondral cyst formation, mechanical malalignment, and ultimately progression to arthroplasty. Medical treatments, such as prostacyclin and bisphosphonate therapy, have shown promise. Alignment procedures, as well as core decompression and subchondroplasty, have been used as surgical treatments for chronic BMLs.

  15. Periosteum and bone marrow in bone lengthening: a DEXA quantitative evaluation in rabbits.

    PubMed

    Guichet, J M; Braillon, P; Bodenreider, O; Lascombes, P

    1998-10-01

    We quantitatively studied the role of periosteum and bone marrow-endosteum during lengthening in 18 growing rabbits, comparing four surgical procedures: 1) periosteum and bone marrow preservation, 2) periosteum preservation, bone marrow destruction, 3) periosteum destruction, bone marrow preservation, 4) periosteum and bone marrow destruction. An external fixator was set on one femur, the other serving as a control. Distraction began on day 5 and stopped on day 25 (0.25 mm/12 hours). On day 30, femora were harvested with a layer of muscle. Area, bone mineral content and density were measured by dual-energy x-ray absorptiometry. Procedure 2 showed the highest increase in bone mineral content around the elongated callus (127%) compared to procedures: 1 (81%), 3 (25%) and 4 (-8%, i.e., resorption of bone ends). A statistically significant effect on bone formation was observed when preserving (vs. destroying): 1) periosteum, 2) bone marrow (effect observed only around the distraction gap), 3) periosteum and bone marrow in combination. Periosteum alone forms a larger callus, with more mineral content than bone marrow alone, and destruction of both results in the absence of bone formation around the distraction area. Careful preservation of periosteum is essential to bone healing. Formation of bone with a large mineral content does not require bone marrow preservation, but there is an interaction effect on healing between bone marrow and periosteum.

  16. COMPARATIVE STUDY OF BONE NEOFORMATION USING AUTOLOGOUS GRAFTING AND THREE REPLACEMENTS: BONE DEFECTS IN RATS

    PubMed Central

    Stein, Rodrigo Steffen; Silva, Jefferson Braga; Silva, Vinicius Duval da

    2015-01-01

    Objective: Compare the percentage of bone neoformation promoted by autologous bone grafting and three kinds of replacement materials with different characteristics in rats' femoral holes. Methods: Two holes measuring 5.4×2.7mm, were produced on each femur (right and left) of 14 isogenic Wistar rats. Each of the four defects produced was filled by autologous bone or by one of three tested materials-hydroxyapatite (HA), Genphos® (HA+ β-TCP) and GenMix® (a combined bovine bone graft). In the end of the 6-week (n = 6) and 12-week (n = 8) periods, the animals were sacrificed. The sections (stained with Picro-Sirius) were assessed by optical microscopy and specific software. Results: The groups with autologous bone were shown to be significantly superior to the others at both assessed times, showing a mean bone formation rate ± SD of 90.6 ± 10.8% in six weeks, and 98 ± 9.2% in 12 weeks (p > 0.0001 for both assessed times). In six weeks, the results for the other groups were the following: Genphos®, 46 ± 7.1%; HA, 43.1 ± 8.4%; and GenMix®, 57.3 ± 4.5%. In 12 weeks: Genphos®, 47.8 ± 11.1%; HA, 39.9 ± 5.4%; GenMix®, 59.7 ± 4.8%, significant (p = 0.007). Conclusions: In both assessed times, the three bone replacement materials tested in the study showed to be inferior to autologous bone graft for bone neoformation percentage. PMID:27022515

  17. Bone marrow and bone marrow derived mononuclear stem cells therapy for the chronically ischemic myocardium

    SciTech Connect

    Waksman, Ron; Baffour, Richard

    2003-09-01

    Bone marrow stem cells have been shown to differentiate into various phenotypes including cardiomyocytes, vascular endothelial cells and smooth muscle. Bone marrow stem cells are mobilized and home in to areas of injured myocardium where they are involved in tissue repair. In addition, bone marrow secretes multiple growth factors, which are essential for angiogenesis and arteriogenesis. In some patients, these processes are not enough to avert clinical symptoms of ischemic disease. Therefore, in vivo administration of an adequate number of stem cells would be a significant therapeutic advance. Unfractionated bone marrow derived mononuclear stem cells, which contain both hematopoietic and nonhematopoietic cells may be more appropriate for cell therapy. Studies in animal models suggest that implantation of different types of stem cells improve angiogenesis and arteriogenesis, tissue perfusion as well as left ventricular function. Several unanswered questions remain. For example, the optimal delivery approach, dosage and timing of the administration of cell therapy as well as durability of improvements need to be studied. Early clinical studies have demonstrated safety and feasibility of various cell therapies in ischemic disease. Randomized, double blind and placebo-controlled clinical trials need to be completed to determine the effectiveness of stem cell.

  18. Bone marrow-derived dendritic cells.

    PubMed

    Roney, Kelly

    2013-01-01

    While much is understood about dendritic cells and their role in the immune system, the study of these cells is critical to gain a more complete understanding of their function. Dendritic cell isolation from mouse body tissues can be difficult and the number of cells isolated small. This protocol describes the growth of large number of dendritic cells from the culture of mouse bone marrow cells. The dendritic cells grown in culture facilitate experiments that may require large number of dendritic cells without great expense or use of large number of mice.

  19. Androgen, Estrogen and the Bone Marrow Microenvironment

    DTIC Science & Technology

    2009-12-01

    binding protein-5 expression. Xu C, Graf LF, Fazli L, Coleman IM, Mauldin DE, Li D, Nelson PS, Gleave M, Plymate SR, Cox ME, Torok-Storb BJ, Knudsen BS...Meeting presentations: Xu C, Graf LF, Fazli L, Nelson PS, Plymate SR, Cox ME, Torok-Storb BJ, Knudsen BS (2007) Androgen-regulation of the Bone...Marrow Microenvironment targets IGFBP-5. Innovative Minds in Prostate Cancer Today (IMPaCT). Atlanta, Georgia. P8-7. Xu C, Graf LF, Fazli L

  20. [Fundamental study of blood and bone marrow].

    PubMed

    Miura, Ikuo

    2009-10-01

    The WHO classification incorporated recent advances of immunology, cytogenetics, and molecular biology, which developed from FAB classification based on cell morphology and cytochemistry. One of the most distinct changes was "AML with recurrent genetic abnormalities." The immunological and cytogenetic studies are required to apply the classification to hematopoietic and lymphoid neoplasms in addition to conventional examinations of the blood and bone marrow. The fundamentals of specimen collection, cell counts, morphologic analysis of blood cells, special stains and other laboratory studies were described in related to the management of myeloid leukemias.

  1. [Modified method for whole bone marrow adherent culture of human bone marrow mesenchymal stem cells].

    PubMed

    Wang, Xiao-Qing; Zhong, Zhao-Dong; Chen, Zhi-Chao; Zou, Ping

    2014-04-01

    This study was aimed to investigate a more convenient and efficient method to cultivate the human bone marrow mesenchymal stem cells by means of natural erythrocyte sedimentation principle, based on the whole bone marrow adherent method. The bone marrow was cultured with a six-well plate instead of the flasks.Firstly, the bone marrow specimen was cultivated with the MSC complete medium for 48 h, then the upper RBC-free supernatant layer was drawn and placed into the new wells to isolate MSC. Inverted microscope was used to observe the cell morphology and to record the adherent time of first cell passage, first passaging time. The traditional whole bone marrow adherent method was used as the control. The cell cycle and cell surface markers were detected by flow cytometry,and the differentiative capacity of MSC into osteocyte and adipocyte was identified by alkaline phosphatase kit and oil red O, respectively. Besides, the proliferative curve of P1,P3,P5 of BMSC was depicted by counting method. The results showed that MSC cultured by the modified method highly expressed CD90, CD105, CD13, CD44 and lowly expressed CD14, CD45, CD34. Concerning the cell cycle feature, it was found that most of the cells were in G0/G1 phase (88.76%) , followed by G2/M phase (3.04%) and S phase (8.2%), which was in accordance with stem cell cycle characteristics. The proliferative curve showed a typical "S" type, and both the oil red O and alkaline phosphatase staining of MSC were positive. Compared with the traditional method, the modified method had the advantage of high adherence rate (P = 0.0001) and shorter passaging time for the first passage (P = 0.001), with the statistically significant difference. It is concluded that there is a large number of adherent, active and suspended MSC in the RBC-free supernatant layer after the culture of bone marrow for 48 h. Isolating MSC by the modified method is more convenient and efficient than the traditional whole bone marrow adherent method.

  2. Common Cold Can Be Dangerous After Bone Marrow Transplant

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164206.html Common Cold Can Be Dangerous After Bone Marrow Transplant Rhinovirus ... 2017 TUESDAY, March 21, 2017 (HealthDay News) -- The common cold can be deadly for patients recovering from bone ...

  3. Schwann cells induce neuronal differentiation of bone marrow stromal cells.

    PubMed

    Zurita, Mercedes; Vaquero, Jesús; Oya, Santiago; Miguel, Miriam

    2005-04-04

    Bone marrow stromal cells are multipotent stem cells that have the potential to differentiate into bone, cartilage, fat and muscle. Recently, bone marrow stromal cells have been shown to have the capacity to differentiate into neurons under specific experimental conditions, using chemical factors. We now describe how bone marrow stromal cells can be induced to differentiate into neuron-like cells when they are co-cultured with Schwann cells. When compared with chemical differentiation, expression of neuronal differentiation markers begins later, but one week after beginning co-culture, most bone marrow stromal cells showed a typical neuronal morphology. Our present findings support the transdifferentiation of bone marrow stromal cells, and the potential utility of these cells for the treatment of degenerative and acquired disorders of the nervous system.

  4. Effects of the bone marrow microenvironment on hematopoietic malignancy.

    PubMed

    Askmyr, Maria; Quach, Julie; Purton, Louise E

    2011-01-01

    The bone marrow (BM) is contained within the bone cavity and is the main site of hematopoiesis, the continuous development of blood cells from immature hematopoietic stem and progenitor cells. The bone marrow consists of developing hematopoietic cells and non-hematopoietic cells, the latter collectively termed the bone marrow microenvironment. These non-hematopoietic cells include cells of the osteoblast lineage, adipocytes and endothelial cells. For many years these bone marrow microenvironment cells were predicted to play active roles in regulating hematopoiesis, and recent studies have confirmed such roles. Importantly, more recent data has indicated that cells of the BM microenvironment may also contribute to hematopoietic diseases. In this review we provide an overview of the roles of the data suggesting that the cells of the bone marrow microenvironment may play an active role in the initiation and progression of hematopoietic malignancy.

  5. Investigation of effect of variations in bone fraction and red marrow cellularity on bone marrow dosimetry in radio-immunotherapy

    NASA Astrophysics Data System (ADS)

    Wilderman, S. J.; Roberson, P. L.; Bolch, W. E.; Dewaraja, Y. K.

    2013-07-01

    A method is described for computing patient-specific absorbed dose rates to active marrow which accounts for spatial variation in bone volume fraction and marrow cellularity. A module has been added to the 3D Monte Carlo dosimetry program DPM to treat energy deposition in the components of bone spongiosa distinctly. Homogeneous voxels in regions containing bone spongiosa (as defined on CT images) are assumed to be comprised only of bone, active (red) marrow and inactive (yellow) marrow. Cellularities are determined from biopsy, and bone volume fractions are computed from cellularities and CT-derived voxel densities. Electrons are assumed to deposit energy locally in the three constituent components in proportions determined by electron energy absorption fractions which depend on energy, cellularity, and bone volume fraction, and which are either taken from the literature or are derived from Monte Carlo simulations using EGS5. Separate algorithms are used to model primary β particles and secondary electrons generated after photon interactions. Treating energy deposition distinctly in bone spongiosa constituents leads to marrow dosimetry results which differ from homogeneous spongiosa dosimetry by up to 20%. Dose rates in active marrow regions with cellularities of 20, 50, and 80% can vary by up to 20%, and can differ by up to 10% as a function of bone volume fraction. Dose to bone marrow exhibits a strong dependence on marrow cellularity and a potentially significant dependence on bone volume fraction.

  6. Investigation of effect of variations in bone fraction and red marrow cellularity on bone marrow dosimetry in radio-immunotherapy.

    PubMed

    Wilderman, S J; Roberson, P L; Bolch, W E; Dewaraja, Y K

    2013-07-21

    A method is described for computing patient-specific absorbed dose rates to active marrow which accounts for spatial variation in bone volume fraction and marrow cellularity. A module has been added to the 3D Monte Carlo dosimetry program DPM to treat energy deposition in the components of bone spongiosa distinctly. Homogeneous voxels in regions containing bone spongiosa (as defined on CT images) are assumed to be comprised only of bone, active (red) marrow and inactive (yellow) marrow. Cellularities are determined from biopsy, and bone volume fractions are computed from cellularities and CT-derived voxel densities. Electrons are assumed to deposit energy locally in the three constituent components in proportions determined by electron energy absorption fractions which depend on energy, cellularity, and bone volume fraction, and which are either taken from the literature or are derived from Monte Carlo simulations using EGS5. Separate algorithms are used to model primary β particles and secondary electrons generated after photon interactions. Treating energy deposition distinctly in bone spongiosa constituents leads to marrow dosimetry results which differ from homogeneous spongiosa dosimetry by up to 20%. Dose rates in active marrow regions with cellularities of 20, 50, and 80% can vary by up to 20%, and can differ by up to 10% as a function of bone volume fraction. Dose to bone marrow exhibits a strong dependence on marrow cellularity and a potentially significant dependence on bone volume fraction.

  7. A multiscale model of the bone marrow and hematopoiesis

    PubMed Central

    Silva, Ariosto S; Anderson, Alexander R.A.

    2013-01-01

    The bone marrow is necessary for renewal of all hematopoietic cells and critical for maintenance of a wide range of physiologic functions. Multiple human diseases result from bone marrow dysfunction. It is also the site in which “liquid” tumors, including leukemia and multiple myeloma, develop as well as a frequent site of metastases. Understanding the complex cellular and microenvironmental interactions that govern normal bone marrow function as well as diseases and cancers of the bone marrow would be a valuable medical advance. Our goal is the development of a spatially-explicit in silico model of the bone marrow to understand both its normal function and the evolutionary dynamics that govern the emergence of bone marrow malignancy. Here we introduce a multiscale computational model of the bone marrow that incorporates three distinct spatial scales, cell, hematopoietic subunit, whole marrow. Implemented as a fixed lattice 3D cellular automaton, it reproduces the spatial characteristics of the normal bone marrow and is validated against data from the daily production of mature blood cells and response of hematopoiesis after irradiation. The major mechanisms modeled in this work are: (1) replication, specialization and migration of hematopoietic cells, (2) optimized spatial configuration of sinuses and hematopoietic compartments and, (3) intravasation of mature hematopoietic cells into sinuses. Our results, using parameter estimates from literature, recapitulates normal bone marrow function and suggest an explanation for the fractal-like structure of trabeculae and sinuses in the marrow, which would be an optimization of the hematopoietic function in order to maximize the number of mature blood cells produced daily within the volumetric restrictions of the marrow. PMID:21631151

  8. Retroviral-mediated transfer of the human glucocerebrosidase gene into cultured Gaucher bone marrow.

    PubMed Central

    Nolta, J A; Yu, X J; Bahner, I; Kohn, D B

    1992-01-01

    Gaucher disease, a lysosomal glycolipid storage disorder, results from the genetic deficiency of an acidic glucosidase, glucocerebrosidase (GC). The beneficial effects of allogeneic bone marrow transplantation (BMT) for Gaucher disease suggest that GC gene transduction and the transplantation of autologous hematopoietic stem cells (gene therapy) may similarly alleviate symptoms. We have constructed a retroviral vector, L-GC, produced by a clone of the amphotropic packaging cell line PA317, which transduces the normal human GC cDNA with high efficiency. Whole-marrow mononuclear cells and CD34-enriched cells from a 4-yr-old female with type 3 Gaucher disease were transduced by the L-GC vector and studied in long-term bone marrow culture (LTBMC). Prestimulation of marrow with IL-3 and IL-6, followed by co-cultivation with vector-producing fibroblasts, produced gene transfer into 40-45% of the hematopoietic progenitor cells. The levels of GC expression in progeny cells (primarily mature myelomonocytic) produced by the LTBMC were quantitatively analyzed by Northern blot, Western blot, and glucocerebrosidase enzyme assay. Normal levels of GC RNA, immunoreactive protein, and enzymatic activity were detected throughout the duration of culture. These studies demonstrate that retroviral vectors can efficiently transfer the GC gene into long-lived hematopoietic progenitor cells from the bone marrow of patients with Gaucher disease and express physiologically relevant levels of GC enzyme activity. Images PMID:1379609

  9. [Frontiers in Live Bone Imaging Researches. In vivo imaging of bone marrow microenvironment].

    PubMed

    Mizuno, Hiroki; Ishii, Masaru

    2015-06-01

    The function of hematopoietic stem cells and leukemia stem cells depends on their interaction with complex microenvironment within the bone marrow. Conventional methods could not observe the dynamic cell movement in living bone marrow. Recently rapid development of live imaging techniques enables us to understand the cellular interaction. Intravital two-photon imaging is the ideal method to understand the nature of bone marrow because of visualizing the cellular dynamics in vivo and observing the bone marrow long time. Here we show the latest reports about bone marrow microenvironment by intravital imaging, and also discuss its further application.

  10. [Method for concentrating marrow stem cells using the IBM 2991 washer. Necessary preparation before in vitro treatment of bone marrow by pharmacologic or immunologic means].

    PubMed

    Hervé, P; Coffe, C; Peters, A

    1983-04-01

    The technique using the IBM 2991 blood cell processor is an effective technique for the concentration of mononuclear cells from large volumes of bone marrow. The marrow cells are layered on to Ficoll Metrizoate using the IBM processing set. The mononuclear cells and CFU-GM recoveries are in close relationship with the hematocrit of the cell suspension processed. Twenty two bone marrows have been collected and purified according to this protocol. The mononuclear cell recovery is an average of 78,3% (range: 44-92%) and the CFU-GM recovery is in average of 67,5% (range: 40-89%). At the end of the procedure the cell viability is satisfying (97,1% +/- 1,7 are trypan blue negatives). When it is necessary to remove from the bone marrow collected either malignant cells prior autologous bone marrow graft or T lymphocytes in an attempt to prevent GVHD in allogeneic BMT, the purity of marrow cell suspension become a fundamental parameter.

  11. Enteral nutrition after bone marrow transplantation

    PubMed Central

    Papadopoulou, A; MacDonald, A; Williams, M; Darbyshire, P; Booth, I

    1997-01-01

    Accepted 16 April 1997
 Nutritional insult after bone marrow transplantation (BMT) is complex and its nutritional management challenging. Enteral nutrition is cheaper and easier to provide than parenteral nutrition, but its tolerance and effectiveness in reversing nutritional depletion after BMT is poorly defined. Nutritional status, wellbeing, and nutritional biochemistry were prospectively assessed in 21 children (mean age 7.5 years; 14 boys) who received nasogastric feeding after BMT (mean duration 17 days) and in eight children (mean age 8 years, four boys) who refused enteral nutrition and who received dietetic advice only.
 Enteral nutrition was stopped prematurely in eight patients. Greater changes in weight and mid upper arm circumference were observed in the enteral nutrition group, while positive correlations were found between the duration of feeds and increase in weight and in mid upper arm circumference. Vomiting and diarrhoea had a similar incidence in the two groups, while fever and positive blood cultures occurred more frequently in the dietetic advice group. Diarrhoea occurring during enteral nutrition was not associated with fat malabsorption, while carbohydrate malabsorption was associated with rotavirus infection only. Enteral feeding did not, however, affect bone marrow recovery, hospital stay, general wellbeing, or serum albumin concentrations. Hypomagnesaemia, hypophosphataemia, zinc and selenium deficiency were common in both groups. In conclusion, enteral nutrition, when tolerated, is effective in limiting nutritional insult after BMT. With existing regimens nutritional biochemistry should be closely monitored in order to provide supplements when required.

 PMID:9301351

  12. Aerobic nitroreduction of dehydrochloramphenicol by bone marrow.

    PubMed

    Isildar, M; Abou-Khalil, W H; Jimenez, J J; Abou-Khalil, S; Yunis, A A

    1988-06-30

    It has been previously demonstrated that dehydrochloramphenicol (DH-CAP), a bacterial metabolite of chloramphenicol, induces DNA single strand breaks in intact cells and is profoundly more cytotoxic than chloramphenicol (CAP). In view of previous observations relating genotoxicity of nitrocompounds to their nitroreduction by the target tissue, we studied the nitroreduction of DH-CAP by human and rabbit bone marrow. Nitroreduction by tissue homogenates was determined by the Bratton Marshall colorimetric assay and by high-performance liquid chromatography (HPLC). Nitroreduction of DH-CAP by bone marrow cell homogenates was observed under aerobic conditions and the reduction was both cell concentration- and time-dependent. The formation of the amino product aminodehydrochloramphenicol was confirmed by HPLC. Reduction by other tissues including human liver, Raji cells, and HL-60 tumors was also observed. These results suggest that genotoxicity of DH-CAP may be related to its nitroreduction by the target tissue with in situ production of toxic intermediates. Together with previous studies, these observations lend support to the thesis that the p-NO2 group may be the structural feature underlying aplastic anemia from CAP.

  13. Autologous mesenchymal stem cell (MSCs) transplantation for critical-sized bone defect following a wide excision of osteofibrous dysplasia

    PubMed Central

    Dilogo, Ismail Hadisoebroto; Kamal, Achmad Fauzi; Gunawan, Bambang; Rawung, Rangga Valentino

    2015-01-01

    Introduction Osteofibrous dysplasia is a rare non-neoplastic disease that is almost exclusive to pediatric tibial diaphysis. Wide excision of the lesion is recommended to avoid recurrence. However, such radical surgery will results in large segmental bone defects that will require further extensive reconstructive surgery. We report a novel approach of treating bone defect by implementing the diamond concept of bone healing using autologous bone marrow derived mesenchymal stem cells (BM-MSCs). Presentation of case An eight-year-old Indonesian male presented with severe bowing deformity of the left lower leg. Radiographic and histological analysis confirmed the diagnosis of osteofibrous dysplasia. A wide excision of the defect was made leaving a critical-sized bone defect. A combination of autologous transplantation of 50 million BM-MSCs, hydroxyapatite (HA) granules, bone morphogenic protein 2 (BMP-2) and Djoko-Zarov hybrid circular external fixator was used to treat the defect. The outcomes measured were subjective complaints, functionality based on LEFS and radiological assessments. Discussion Radiographic assessments showed successful new bone tissue formation and integration of implanted HA granules. The external fixator was removed at 42 weeks after adequate callus formation and clinical stability was achieved. The patient underwent progressive functional improvements and reached a near normal functionality of 90% LEFS at 84 week. No therapy side effect or complication was reported. Conclusion Osteofibrous dysplasia was successfully excised without signs of recurrence after 84-week follow-up. Autologous transplantation of augmented BM-MSCs has successfully created new normal bone tissue without causing any side effect and had significantly improved the patient’s quality of life. PMID:26599503

  14. The Procuring and Processing of Human Cadaveric Bone Marrow

    DTIC Science & Technology

    1990-01-01

    PROCESSING OF HUMAN CADAVERIC BONE MARROW 12. PERSONAL AUTHOR(S) Timothy R. Faloon 13a. TYPE OF REPORT 13b. TIMECiOVED 14. DATE OF REPORT (Year, Month, Day) S...CADAVERIC BONE MARROW PROCESSING PROTOCOL ................ 15 Procedure for processing and freezing . .................................. 15 CELL VIABILITY...18 Procedure . ....................................................... 18 USING THE COULTER COUNTER

  15. Vertebral hyperemia associated with bone marrow insult and recovery

    SciTech Connect

    Klein, H.A.; Bolden, R.O.; Simone, F.J.

    1984-06-01

    A 15-year-old boy with rhabdoid sarcoma received chemotherapy, which was followed by bone marrow depression, massive nosebleeds and, finally, hematologic recovery. On both hepatobiliary and renal scintigraphy, prominent vertebral activity was present in early images. Correlation with his clinical course suggests that the findings reflect hyperemia due to marrow insult and recovery. Radionuclide imaging to detect hyperemia may be a useful probe for drug effects on hematopoietic bone marrow.

  16. Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration.

    PubMed

    Colnot, Céline

    2009-02-01

    Bone repair requires the mobilization of adult skeletal stem cells/progenitors to allow deposition of cartilage and bone at the injury site. These stem cells/progenitors are believed to come from multiple sources including the bone marrow and the periosteum. The goal of this study was to establish the cellular contributions of bone marrow and periosteum to bone healing in vivo and to assess the effect of the tissue environment on cell differentiation within bone marrow and periosteum. Results show that periosteal injuries heal by endochondral ossification, whereas bone marrow injuries heal by intramembranous ossification, indicating that distinct cellular responses occur within these tissues during repair. [corrected] Next, lineage analyses were used to track the fate of cells derived from periosteum, bone marrow, and endosteum, a subcompartment of the bone marrow. Skeletal progenitor cells were found to be recruited locally and concurrently from periosteum and/or bone marrow/endosteum during bone repair. Periosteum and bone marrow/endosteum both gave rise to osteoblasts, whereas the periosteum was the major source of chondrocytes. Finally, results show that intrinsic and environmental signals modulate cell fate decisions within these tissues. In conclusion, this study sheds light into the origins of skeletal stem cells/progenitors during bone regeneration and indicates that periosteum, endosteum, and bone marrow contain pools of stem cells/progenitors with distinct osteogenic and chondrogenic potentials that vary with the tissue environment.

  17. Bone marrow lesions and subchondral bone pathology of the knee.

    PubMed

    Kon, Elizaveta; Ronga, Mario; Filardo, Giuseppe; Farr, Jack; Madry, Henning; Milano, Giuseppe; Andriolo, Luca; Shabshin, Nogah

    2016-06-01

    Bone marrow lesions (BMLs) around the knee are a common magnetic resonance imaging (MRI) finding. However, despite the growing interest on BMLs in multiple pathological conditions, they remain controversial not only for the still unknown role in the etiopathological processes, but also in terms of clinical impact and treatment. The differential diagnosis includes a wide range of conditions: traumatic contusion and fractures, cyst formation and erosions, hematopoietic and infiltrated marrow, developmental chondroses, disuse and overuse, transient bone marrow oedema syndrome and, lastly, subchondral insufficiency fractures and true osteonecrosis. Regardless the heterogeneous spectrum of these pathologies, a key factor for patient management is the distinction between reversible and irreversible conditions. To this regard, MRI plays a major role, leading to the correct diagnosis based on recognizable typical patterns that have to be considered together with coexistent abnormalities, age, and clinical history. Several treatment options have been proposed, from conservative to surgical approaches. In this manuscript the main lesion patterns and their management have been analysed to provide the most updated evidence for the differential diagnosis and the most effective treatment.

  18. Quality of life-adjusted survival analysis of high-dose therapy with autologous bone marrow transplantation versus sequential chemotherapy for patients with aggressive lymphoma in first complete remission. Groupe d'Etude les Lymphomes de l'Adulte (GELA).

    PubMed

    Mounier, N; Haioun, C; Cole, B F; Gisselbrecht, C; Sebban, C; Morel, P; Marit, G; Bouabdallah, R; Ravoet, C; Salles, G; Reyes, F; Lepage, E

    2000-06-15

    Evaluating high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) in term of both duration and quality of life (QOL) presents major interests for patients with non-Hodgkin lymphoma. The quality-adjusted time without symptom and toxicity (Q-TWiST) methodology was applied to the LNH87-2 trial comparing HDT with ASCT versus sequential chemotherapy in 541 patients in first complete remission (CR). Overall survival (OS) and disease-free survival (DFS) curves were used to estimate duration of 4 health states: acute short-term toxicity (Tox1), secondary toxicity (Tox2), time without symptom and toxicity (TWiST), and relapse (Rel). Areas under survival curves (AUC) were retrospectively weighted according to QOL coefficients. HDT increased, but not significantly, TWiST (+2. 4 months in AUC, P =.17) and decreased Rel (-3 months, P <.01). Survival estimates did not differ between the 2 treatments (AUC 47.7 months for OS, 39.7 months for DFS). High-risk patients treated by HDT versus chemotherapy had a significant benefit in DFS (AUC 28.8 versus 24.9 months, P <.01) but not in OS (AUC 37.3 versus 36 months, P =.27). Sensitivity analysis, performed by varying QOL coefficients, demonstrated significant quality-adjusted survival gain in high-risk patients treated by HDT. In low-risk patients, a diagram provided an aid to clinical decision-making. This analysis supports the use of HDT in these patients with adverse prognostic factors in the first CR, even after adjusting for QOL using the Q-TWiST method. (Blood. 2000;95:3687-3692)

  19. Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

    PubMed Central

    Piccinin, Meghan A; Khan, Zia A

    2014-01-01

    Diabetes leads to complications in select organ systems primarily by disrupting the vasculature of the target organs. These complications include both micro- (cardiomyopathy, retinopathy, nephropathy, and neuropathy) and macro-(atherosclerosis) angiopathies. Bone marrow angiopathy is also evident in both experimental models of the disease as well as in human diabetes. In addition to vascular disruption, bone loss and increased marrow adiposity have become hallmarks of the diabetic bone phenotype. Emerging evidence now implicates enhanced marrow adipogenesis and changes to cellular makeup of the marrow in a novel mechanistic link between various secondary complications of diabetes. In this review, we explore the mechanisms of enhanced marrow adipogenesis in diabetes and the link between changes to marrow cellular composition, and disruption and depletion of reparative stem cells. PMID:26317050

  20. Non-myeloablative bone marrow transplantation.

    PubMed

    Ruiz-Argüelles, Guillermo J

    2003-01-01

    As a result of the evolution of knowledge in the area of allogeneic hematopoietic stem cells (HSC) transplantation, several dogmata have been broken. We now have the following information: a) successful engraftment if allogeneic HSC bone marrow ablation of the recipient is not required; b) HSC create their own space through graft-vs.-host reactions; c) several malignancies are eradicated by the graft-vs.-tumor effect; d) allografting can be conducted on an out-patient basis; e) allografting can be done in aged or debilitated individuals; f) allografting can be achieved without transfusion of blood products, and g) costs of the allografting procedures can be substantially diminished. Breaking all these dogmata has resulted in availability of HSC allografting to a larger number of individuals, thus offering true curative therapeutic options to patients who otherwise would not qualify to receive these opportunities.

  1. Guided bone regeneration in pig calvarial bone defects using autologous mesenchymal stem/progenitor cells - a comparison of different tissue sources.

    PubMed

    Stockmann, Philipp; Park, Jung; von Wilmowsky, Cornelius; Nkenke, Emeka; Felszeghy, Endre; Dehner, Jan-Friedrich; Schmitt, Christian; Tudor, Christian; Schlegel, Karl Andreas

    2012-06-01

    Due to donor side morbidity and the absence of osteogenic properties in bone substitutes, there is a growing need for an alternative to traditional bone grafting within the scope of tissue engineering. This animal study was conducted to compare the in vivo osteogenic potential of adipose-derived (AD), periosteum-derived (PD) and bone marrow-derived (BM) mesenchymal stem/progenitor cells (MSC). Autologous mesenchymal stem/progenitor cells of named tissue origin were induced into osteogenic differentiation following in vitro cell expansion. Ex vivo cultivated cells were seeded on a collagen scaffold and subsequently added to freshly created monocortical calvarial bone defects in 21 domestic pigs. Pure collagen scaffold served as a control defect. The animals were sacrificed at specific time points and de novo bone formation was quantitatively analyzed by histomorphometry. Bone volume/total defect volume (BV/TV) and the mineralization rate of newly formed bone were compared among the groups. In the early stages of wound healing, up to 30 days, the test defects did not show better bone regeneration than those in the control defect, but the bone healing process in the test defects was accelerated in the later stage compared to those in the control defect. All the test defects showed complete osseous healing after 90 days compared to those in the control defect. During the observation period, no significant differences in BV/TV and mineralization of newly formed bone among the test defects were observed. Irrespective of the tissue sources of MSC, the speed and pattern of osseous healing after cell transplantations into monocortical bone defects were comparable. Our results indicate that the efficiency of autologous AD-MSC, PD-MSC and BM-MSC transplantation following ex vivo cell expansion is not significantly different for the guided regeneration of bone defects.

  2. Reaming debris as a novel source of autologous bone to enhance healing of bone defects.

    PubMed

    Bakker, Astrid D; Kroeze, Robert Jan; Korstjens, Clara; de Kleine, Ruben H; Frölke, Jan Paul M; Klein-Nulend, Jenneke

    2011-06-15

    Reaming debris is formed when bone defects are stabilized with an intramedullary nail, and contains viable osteoblast-like cells and growth factors, and might thus act as a natural osteoinductive scaffold. The advantage of using reaming debris over stem cells or autologous bone for healing bone defects is that no extra surgery is needed to obtain the material. To assess the clinical feasibility of using reaming debris to enhance bone healing, we investigated whether reaming debris enhances the healing rate of a bone defect in sheep tibia, compared to an empty gap. As golden standard the defect was filled with iliac crest bone. Bones treated with iliac crest bone and reaming debris showed larger callus volume, increased bone volume, and decreased cartilage volume in the fracture gap, and increased torsional toughness compared to the empty gap group at 3 weeks postoperative. In addition, bones treated with reaming debris showed increased torsional stiffness at 6 weeks postoperatively compared to the empty defect group, while bending stiffness was marginally increased. These results indicate that reaming debris could serve as an excellent alternative to iliac crest bone for speeding up the healing process in bone defects that are treated with an intramedullary nail.

  3. [Acute renal failure secondary to hepatic veno-occlusive disease in a bone marrow transplant patient].

    PubMed

    Borrego, F J; Viedma, G; Pérez del Barrio, P; Gil, J M; de Santis-Scoccia, C; Ramírez Huerta, J M; Alcalá, A; Pérez Bañasco, V

    2003-01-01

    Acute renal failure following bone marrow transplantation is a frequent complication with an incidence ranging 15-30% and with high rates of morbidity and mortality. Numerous potential etiologies can be implicated as chemotherapy regimen, use of nephrotoxic antibiotics, sepsis-induced damage, cyclosporine toxicity and other especific pathologies as graft-v-host disease or veno-occlusive disease of the liver. We report the case of a 41-year-old man who underwent autologous peripheral blood stem cell transplantation and developed and acute renal failure secondary to a fatal veno-occlusive disease of the liver. Incidence, potential predisposing factors, outcome and possibilities of treatment are reviewed.

  4. Successful treatment of refractory acquired pure red cell aplasia (PRCA) by allogeneic bone marrow transplantation.

    PubMed

    Müller, B U; Tichelli, A; Passweg, J R; Nissen, C; Wodnar-Filipowicz, A; Gratwohl, A

    1999-06-01

    This case describes a 16-year-old woman treated successfully by a bone marrow transplant from her HLA-identical brother for refractory acquired pure red cell aplasia. Conditioning was as for severe aplastic anaemia with cyclophosphamide 4 x 50 mg/kg and antithymocyte globulin. Complete donor type engraftment at 3 months reversed to full autologous reconstitution at 2 years with normal haemopoiesis. The potential implications on pathogenesis of the disease as well as on treatment of autoimmune disorders by stem cell transplantation are discussed.

  5. Bone marrow modified acrylic bone cement for augmentation of osteoporotic cancellous bone.

    PubMed

    Arens, Daniel; Rothstock, Stephan; Windolf, Markus; Boger, Andreas

    2011-11-01

    The use of polymethylmethacrylate (PMMA) cement to reinforce fragile or broken vertebral bodies (vertebroplasty) leads to extensive bone stiffening. This might be one reason for fractures at the adjacent vertebrae following this procedure. PMMA with a reduced Young's modulus may be more suitable. The goal of this study was to produce and characterize PMMA bone cements with a reduced Young's modulus by adding bone marrow. Bone cements were produced by combining PMMA with various volume fractions of freshly harvested bone marrow from sheep. Porosity, Young's modulus, yield strength, polymerization temperature, setting time and cement viscosity of different cement modifications were investigated. The samples generated comprised pores with diameters in the range of 30-250 μm leading to porosity up to 51%. Compared to the control cement, Young's modulus and yield strength decreased from 1830 to 740 MPa and from 58 to 23 MPa respectively by adding 7.5 ml bone marrow to 23 ml premixed cement. The polymerization temperature decreased from 61 to 38 ∘C for cement modification with 7.5 ml of bone marrow. Setting times of the modified cements were lower in comparison to the regular cement (28 min). Setting times increased with higher amounts of added bone marrow from around 16-25 min. The initial viscosities of the modified cements were higher in comparison to the control cement leading to a lower risk of extravasation. The hardening times followed the same trend as the setting times. In conclusion, blending bone marrow with acrylic bone cement seems to be a promising method to increase the compliance of PMMA cement for use in cancellous bone augmentation in osteoporotic patients due to its modified mechanical properties, lower polymerization temperature and elevated initial viscosity.

  6. Single high-dose etoposide and melphalan with non-cryopreserved autologous marrow rescue as primary therapy for relapsed, refractory and poor-prognosis Hodgkin's disease.

    PubMed Central

    Seymour, L. K.; Dansey, R. D.; Bezwoda, W. R.

    1994-01-01

    A simplified schedule of high-dose chemotherapy (HDC) consisting of melphalan (140 mg m-2) plus VP16 (2.5 g m-2) given over 12-18 h together with autologous non-cryopreserved autologous bone marrow transplant (ABMT) was used for treatment of relapsed (37 patients) and refractory (seven patients) patients and as first-line treatment (four patients) for poor-prognosis Hodgkin's disease. Two patients had a second HDC-ABMT after relapse following prior HDC-ABMT, giving a total of 50 procedures among 48 patients. The haematological recovery rate was 98% with a complete response rate of the Hodgkin's disease of > 90%. Factors significantly influencing response rate were performance status and the presence of liver involvement. Thirty-nine patients are alive, with 37 in continuous complete remission. The median duration of survival and median duration of remission have not been reached at a median follow-up time of 45 months. Adverse prognostic factors for survival were disease status at the time of HDC-ABMT (refractory versus relapse, with primarily refractory patients showing significantly poor survival) and the presence of liver involvement. High-dose chemotherapy with short-duration chemotherapy and non-cryopreserved bone marrow is an effective and safe treatment modality for patients with relapsed and poor-prognosis Hodgkin's disease. PMID:8080741

  7. Marrow-tumor interactions: the role of the bone marrow in controlling chemically induced tumors

    SciTech Connect

    Rosse, C

    1980-01-01

    This report summarizes work done to evaluate the role of the bone marrow in tumor growth regulation. Work done with the MCA tumor showed that several subclasses of mononuclear bone marrow cells (e.g. natural regulatory cell, NRC) play a major role in the regulation of tumor growth. Experiments with the spontaneous CE mammary carcinoma system illustrate that a rapid growth of certain neoplasms may be due to the fact that through some as yet undefined mechanism the tumor eliminates mononuclear cells in the bone marrow of the host and stops their production. (KRM)

  8. Marrow stromal fibroblastic cell cultivation in vitro on decellularized bone marrow extracellular matrix.

    PubMed

    Dutra, Timothy F; French, Samuel W

    2010-02-01

    The in vitro biocompatibility of decellularized bone marrow extracellular matrix was evaluated. Following a freeze-thaw cycle, sectioned discs of fresh frozen rat metaphyseal bone were sequentially incubated in solutions of hypertonic, then hypotonic Ringer's solution, followed by deoxycholic acid, then DNAase I. The adequacy of decellularization of marrow stroma was examined by light microscopy. Marrow stromal fibroblastic cells were harvested by dispersion of rat long bone marrow, followed by concentration by discontinuous Ficoll-Paque gradient centrifugation. The fibroblastic cells were expanded by in vitro cultivation, and second passage cells were cryopreserved until needed. Cryopreserved marrow stromal cells were applied dropwise to sections of decellularized bone marrow extracellular matrix, and cultured in BJGb medium with 20% fetal bovine serum for ten days. Mature cultures were formalin fixed, decalcified, and embedded in paraffin. Light microscopy of hematoxylin and eosin stained sections showed individual spindle cells invading the upper portion of the decellularized extracellular matrix, and also a monolayer of spindle cells on the upper surfaces of exposed trabecular and cortical bone. This experiment showed that decellularized marrow extracellular matrix is a biocompatible three dimensional in vitro substrate for marrow stromal fibroblastic cells.

  9. Three-dimensional polycaprolactone-hydroxyapatite scaffolds combined with bone marrow cells for cartilage tissue engineering.

    PubMed

    Wei, Bo; Yao, Qingqiang; Guo, Yang; Mao, Fengyong; Liu, Shuai; Xu, Yan; Wang, Liming

    2015-08-01

    The goal of this study was to investigate the chondrogenic potential of three-dimensional polycaprolactone-hydroxyapatite (PCL-HA) scaffolds loaded with bone marrow cells in vitro and the effect of PCL-HA scaffolds on osteochondral repair in vivo. Here, bone marrow was added to the prepared PCL-HA scaffolds and cultured in chondrogenic medium for 10 weeks. Osteochondral defects were created in the trochlear groove of 29 knees in 17 New Zealand white rabbits, which were then divided into four groups that underwent: implantation of PCL-HA scaffolds (left knee, n = 17; Group 1), microfracture (right knee, n = 6; Group 2), autologous osteochondral transplantation (right knee, n = 6; Group 3), and no treatment (right knee, n = 5; Control). Extracellular matrix produced by bone marrow cells covered the surface and filled the pores of PCL-HA scaffolds after 10 weeks in culture. Moreover, many cell-laden cartilage lacunae were observed, and cartilage matrix was concentrated in the PCL-HA scaffolds. After a 12-week repair period, Group 1 showed excellent vertical and lateral integration with host bone, but incomplete cartilage regeneration and matrix accumulation. An uneven surface of regenerated cartilage and reduced distribution of cartilage matrix were observed in Group 2. In addition, abnormal bone growth and unstable integration between repaired and host tissues were detected. For Group 3, the integration between transplanted and host cartilage was interrupted. Our findings indicate that the PCL-HA scaffolds loaded with bone marrow cells improved chondrogenesis in vitro and implantation of PCL-HA scaffolds for osteochondral repairenhanced integration with host bone. However, cartilage regeneration remained unsatisfactory. The addition of trophic factors or the use of precultured cell-PCL-HA constructs for accelerated osteochondral repair requires further investigation.

  10. Primary Splenic Angiosarcoma Revealed by Bone Marrow Metastasis

    PubMed Central

    Anoun, Soumaya; Marouane, Sofia; Quessar, Asmae; Benchekroun, Said

    2014-01-01

    Primary splenic angiosarcomas are the most common malignant non-hematopoietic tumors of the spleen. Metastatic diseases were found in 69% of patients in a reported series but the incidence of bone marrow involvement is unclear. We report a rare case of a 25-years-old Moroccan woman with unsuspected primary splenic angiosarcoma revealed by bone marrow metastasis. She presented with serious anemia and splenomegaly. Bone marrow biopsy revealed proliferating spindle cells. Computed tomography scanning showed an enlarged spleen with heterogeneous lesions. Splenectomy was performed and retrospective histological study of the spleen confirmed the diagnosis. She died 1 year after splenectomy. PMID:25541659

  11. Primary splenic angiosarcoma revealed by bone marrow metastasis.

    PubMed

    Anoun, Soumaya; Marouane, Sofia; Quessar, Asmae; Benchekroun, Said

    2014-12-05

    Primary splenic angiosarcomas are the most common malignant non-hematopoietic tumors of the spleen. Metastatic diseases were found in 69% of patients in a reported series but the incidence of bone marrow involvement is unclear. We report a rare case of a 25-years-old Moroccan woman with unsuspected primary splenic angiosarcoma revealed by bone marrow metastasis. She presented with serious anemia and splenomegaly. Bone marrow biopsy revealed proliferating spindle cells. Computed tomography scanning showed an enlarged spleen with heterogeneous lesions. Splenectomy was performed and retrospective histological study of the spleen confirmed the diagnosis. She died 1 year after splenectomy.

  12. Status and prospects of liver cirrhosis treatment by using bone marrow-derived cells and mesenchymal cells.

    PubMed

    Terai, Shuji; Takami, Taro; Yamamoto, Naoki; Fujisawa, Koichi; Ishikawa, Tsuyoshi; Urata, Yohei; Tanimoto, Haruko; Iwamoto, Takuya; Mizunaga, Yuko; Matsuda, Takashi; Oono, Takashi; Marumoto, Miho; Burganova, Guzel; Fernando Quintanilha, Luiz; Hidaka, Isao; Marumoto, Yoshio; Saeki, Issei; Uchida, Koichi; Yamasaki, Takahiro; Tani, Kenji; Taura, Yasuho; Fujii, Yasuhiko; Nishina, Hiroshi; Okita, Kiwamu; Sakaida, Isao

    2014-06-01

    In 2003, we started autologous bone marrow cell infusion (ABMi) therapy for treating liver cirrhosis. ABMi therapy uses 400 mL of autologous bone marrow obtained under general anesthesia and infused mononuclear cells from the peripheral vein. The clinical study expanded and we treated liver cirrhosis induced by HCV and HBV infection and alcohol consumption. We found that the ABMi therapy was effective for cirrhosis patients and now we are treating patients with combined HIV and HCV infection and with metabolic syndrome-induced liver cirrhosis. Currently, to substantiate our findings that liver cirrhosis can be successfully treated by the ABMi therapy, we are conducting randomized multicenter clinical studies designated "Advanced medical technology B" for HCV-related liver cirrhosis in Japan. On the basis of our clinical study, we developed a proof-of-concept showing that infusion of bone marrow cells (BMCs) improved liver fibrosis and sequentially activated proliferation of hepatic progenitor cells and hepatocytes, further promoting restoration of liver functions. To treat patients with severe forms of liver cirrhosis, we continued translational research to develop less invasive therapies by using mesenchymal stem cells derived from bone marrow. We obtained a small quantity of BMCs under local anesthesia and expanded them into mesenchymal stem cells that will then be used for treating cirrhosis. In this review, we present our strategy to apply the results of our laboratory research to clinical studies.

  13. Bone and bone-marrow blood flow in chronic granulocytic leukemia and primary myelofibrosis

    SciTech Connect

    Lahtinen, R.; Lahtinen, T.; Romppanen, T.

    1982-03-01

    Blood flow in hematopoietic bone marrow and in nonhematopoietic bone has been measured with a Xe-133 washout method in 20 patients with chronic granulocytic leukemia (CGL) and in seven with primary myelofibrosis. Age-matched healthy persons served as controls. Bone-marrow blood flow in CGL was dependent upon the phase of the disease. In the metamorphosis phase, bone-marrow blood flow was high compared with that in the well-controlled phase. Apart from the initial phase, the mean values for bone blood flow in CGL were increased compared with the values of the healthy controls. In myelofibrosis the bone blood flow was also increased. Bone-marrow blood flow in these diseases was dependent upon the cellularity of bone marrow as measured morphometrically.

  14. Enhancement by dimethyl myleran of donor type chimerism in murine recipients of bone marrow allografts

    SciTech Connect

    Lapidot, T.; Terenzi, A.; Singer, T.S.; Salomon, O.; Reisner, Y. )

    1989-05-15

    A major problem in using murine models for studies of bone marrow allograft rejection in leukemia patients is the narrow margin in which graft rejection can be analyzed. In mice irradiated with greater than 9 Gy total body irradiation (TBI) rejection is minimal, whereas after administration of 8 Gy TBI, which spares a significant number of clonable T cells, a substantial frequency of host stem cells can also be detected. In current murine models, unlike in humans, bone marrow allograft rejection is generally associated with full autologous hematopoietic reconstitution. In the present study, we investigated the effect of the myeloablative drug dimethyl myleran (DMM) on chimerism status following transplantation of T cell-depleted allogenic bone marrow (using C57BL/6 donors and C3H/HeJ recipients, conditioned with 8 Gy TBI). Donor type chimerism 1 to 2 months post-transplant of 1 to 3 x 10(6) bone marrow cells was markedly enhanced by using DMM one day after TBI and prior to transplantation. Conditioning with cyclophosphamide instead of DMM, in combination with 8 Gy TBI, did not enhance engraftment of donor type cells. Artificial reconstitution of T cells, after conditioning with TBI plus DMM, by adding mature thymocytes, or presensitization with irradiated donor type spleen cells 1 week before TBI and DMM, led to strong graft rejection and consequently to severe anemia. The anti-donor responses in these models were proportional to the number of added T cells and to the number of cells used for presensitization, and they could be neutralized by increasing the bone marrow inoculum.

  15. Infections and immunodeficiency in bone marrow transplantation.

    PubMed

    Tutschka, P J

    1988-05-01

    After allogeneic bone marrow transplantation certain patterns of infectious complications emerge that follow the clinical course, are correlated to the immunobiology of transplantation and are almost predictable in their character and expression. The preparative regimen, designed to generate complete aplasia, will be associated with severe and sometimes life-threatening bacterial infections, predominantly with Gram-negative organisms derived from bowel flora, but also Gram-positive skin saprophytes. In this early aplastic phase, life-threatening viral infections are less common, consisting mainly of herpes simplex and possibly Epstein-Barr stomatitis and BK papovavirus cystitis. Systemic infections with invasive filamentous fungi are rare and are seen only when the induced aplasia is markedly prolonged. Once early marrow recovery has been achieved, systemic infections will generally disappear unless acute graft-vs.-host disease develops. This complication, which will lead to the breakdown of natural barriers such as skin and gastrointestinal epithelium and the marked impairment of all systemic defense mechanisms, can cause polymicrobial infections as well as set the stage for life-threatening viral infections. Such opportunistic viral infections, leading to either interstitial pneumonia or hemorrhagic gastroenteritis, are the major threat in the early recovery phase after engraftment has taken place. Usually caused by cytomegalovirus and rotavirus, respectively, these infections are the primary expression of the severe combined immunodeficiency post transplant, statistically associated with the presence of acute graft-vs.-host disease and amenable to immunologic manipulations. With the recovery of cellular and humoral immune function derived from transplanted donor lymphoid cells, the third phase of infectious complications is reached, covering 3 months to 2 years post grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Bone marrow invasion in multiple myeloma and metastatic disease.

    PubMed

    Vilanova, J C; Luna, A

    2016-04-01

    Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases.

  17. Revision Rotator Cuff Reconstruction for Large Tears With Retraction: A Novel Technique Using Autogenous Tendon and Autologous Marrow.

    PubMed

    Skoff, Hillel D

    2015-07-01

    Revision rotator cuff reconstruction for large tears with retraction results in a high rate of recurrent cuff tearing. To try to obtain more consistent results, I conducted a study of a technique that addresses the potential factors involved. Ten patients (7 men, 3 women) were enrolled. Mean age was 58 years. Mean follow-up was 24 months. Mean time between primary and revision cuff surgery was 36 months. The cardinal inclusion criterion was a symptomatic, full-thickness rotator cuff tear with at least 3 cm of retraction in a shoulder that previously underwent rotator cuff repair. Ultrasound was used for postoperative radiographic assessment of cuff integrity. Validated Constant, American Shoulder and Elbow Surgeons (ASES), and University of California Los Angeles (UCLA) shoulder scoring systems were used. Surgical technique included mini-open incision, adequate débridement and mobilization of remaining cuff, reconstitution of cuff defect with autogenous biceps tendon incubated in concentrated autologous bone marrow, and sewing under zero tissue tension. Constant, ASES, and UCLA scores improved significantly (standard error at .001). Ultrasound revealed 0% incidence of full-thickness rotator cuff retearing. In patients with large recurrent retracted rotator cuff tears the technique presented in the current study consistently yields satisfactory clinical results and promotes rotator cuff tissue healing without full-thickness retearing.

  18. Bone Marrow Diseases - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bone Marrow Diseases URL of this page: https://medlineplus.gov/languages/bonemarrowdiseases.html Other topics A-Z A B ...

  19. Bone marrow infection with Mycobacterium fortuitum in a diabetic patient.

    PubMed

    Satti, Luqman; Abbasi, Shahid; Sattar, Abdul; Ikram, Aamer; Manzar, Muhammad Adnan; Khalid, Malik Muhammad

    2011-08-01

    Incidence and prevalence of Mycobacterium fortuitum infection vary greatly by location and death is very rare except in disseminated disease in immunocompromised individuals. We present what we believe is the first case of bone marrow infection with Mycobacterium fortuitum in an HIV negative patient. Bone marrow examination revealed presence of numerous acid fast bacilli which were confirmed as Mycobacterium fortuitum on culture and by molecular analysis. Patient was managed successfully with amikacin and ciprofloxacin.

  20. In vivo visualizing the dynamics of bone marrow stem cells in mouse retina and choroidal-retinal circulation

    NASA Astrophysics Data System (ADS)

    Wang, Heuy-Ching H.; Zwick, Harry; Edsall, Peter R.; Cheramie, Rachel D.; Lund, David J.; Stuck, Bruce

    2007-02-01

    It has recently been shown that bone marrow cells can differentiate into various lineage cells including neural cells in vitro and in vivo. Therefore it is an attractive therapeutic intervention to apply autologous bone marrow-derived stem cells that may offer neuroprotection to laser-induced retinal injuries. The purpose of this study is to develop a method with which to visualize bone marrow stem cells dynamics in mouse retinal circulation. We have used a physiological method, confocal scanning laser ophthalmoscope (SLO), to track the highly enriched stem/progenitor cells circulating in the retina. Stem cells were enriched by immunomagnetic depletion of cells committed to the T- and B lymphocytic, myeloid and erythorid lineages. CellTracker TM Green-labeled stem cells were injected into the tail veins of mice with laser-induced focal retinal injuries. Bone marrow stem cells labeled with CellTracker TM Green were visible in the retinal circulation for as long as 1 hour and 30 minutes. These studies suggest that stem cell-enriched bone marrow cells may have the ability to mobilize into laser-induced retinal injuries and possibly further proliferate, differentiate and functionally integrate into the retina.

  1. Radioimmune imaging of bone marrow in patients with suspected bone metastases from primary breast cancer

    SciTech Connect

    Duncker, C.M.; Carrio, I.; Berna, L.; Estorch, M.; Alonso, C.; Ojeda, B.; Blanco, R.; Germa, J.R.; Ortega, V. )

    1990-09-01

    Radioimmune imaging of bone marrow was performed by technetium-99m- (99mTc) labeled antigranulocyte monoclonal antibody BW 250/183 (AGMoAb) scans in 32 patients with suspected bone metastases from primary breast cancer. AGMoAb scans showed bone marrow defects in 25/32 (78%) patients; bone invasion was subsequently confirmed in 23 (72%) patients. Conventional bone scans performed within the same week detected bone metastases in 17/32 (53%) patients (p less than 0.001). AGMoAb scans detected more sites indicating metastatic disease than bone scans in 12 of these 17 patients (71%). All patients with bone metastases in the axial skeleton had bone marrow defects at least at the sites of bone metastases. Of 15 patients with normal, or indicative of, benign disease bone scans, 8 patients (53%) presented with bone marrow defects in the AGMoAb scans. Bone invasion was confirmed in six of them. AGMoAb bone marrow scans provide a method for the early detection of bone metastatic invasion in patients with breast cancer and suspected bone metastases.

  2. Solitary haemangioma of the shaft of long bones: resection and reconstruction with autologous bone graft.

    PubMed

    Li, Zhaoxu; Tang, Jicun; Ye, Zhaoming

    2013-04-01

    Bone haemangiomas are uncommon lesions, occurring in the skull or spine. A solitary haemangioma in the diaphysis of a long bone is rare. We retrospectively investigated six patients who presented with a solitary haemangioma in a long bone diaphysis. After segmental bone resection, the bone defect was replaced by a bone autograft. Patients were reviewed clinically and with radiographs. The mean follow-up was 6 years (range : 1-20 years). At the time of latest follow-up, no patient had a recurrence. Postoperative complications were one wound necrosis and one superficial wound infection. Union of the gap filling graft with the host bone was achieved in all patients at an average of 4 months (range: 3-8 months). The average Musculoskeletal Tumor Society functional score was 77% (range: 53%-90%) of normal at 6 months postoperatively, and 97% (range: 95%-99%) at the last follow-up evaluation. Segmental resection for solitary haemangioma and reconstruction with autologous bone graft can be considered as a suitable treatment option.

  3. The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

    PubMed

    Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

    2013-03-01

    Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

  4. Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

    PubMed Central

    Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

    2009-01-01

    Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

  5. Interleukin-15-activated natural killer cells kill autologous osteoclasts via LFA-1, DNAM-1 and TRAIL, and inhibit osteoclast-mediated bone erosion in vitro.

    PubMed

    Feng, Shan; Madsen, Suzi H; Viller, Natasja N; Neutzsky-Wulff, Anita V; Geisler, Carsten; Karlsson, Lars; Söderström, Kalle

    2015-07-01

    Osteoclasts reside on bone and are the main bone resorbing cells playing an important role in bone homeostasis, while natural killer (NK) cells are bone-marrow-derived cells known to play a crucial role in immune defence against viral infections. Although mature NK cells traffic through bone marrow as well as to inflammatory sites associated with enhanced bone erosion, including the joints of patients with rheumatoid arthritis, little is known about the impact NK cells may have on mature osteoclasts and bone erosion. We studied the interaction between human NK cells and autologous monocyte-derived osteoclasts from healthy donors in vitro. We show that osteoclasts express numerous ligands for receptors present on activated NK cells. Co-culture experiments revealed that interleukin-15-activated, but not resting, NK cells trigger osteoclast apoptosis in a dose-dependent manner, resulting in drastically decreased bone erosion. Suppression of bone erosion requires contact between NK cells and osteoclasts, but soluble factors also play a minor role. Antibodies masking leucocyte function-associated antigen-1, DNAX accessory molecule-1 or tumour necrosis factor-related apoptosis-inducing ligand enhance osteoclast survival when co-cultured with activated NK cells and restore the capacity of osteoclasts to erode bone. These results suggest that interleukin-15-activated NK cells may directly affect bone erosion under physiological and pathological conditions.

  6. Spinal nociceptive transmission by mechanical stimulation of bone marrow

    PubMed Central

    Tanaka, Satoshi; Sekiguchi, Takemi; Sugiyama, Daisuke; Kawamata, Mikito

    2016-01-01

    Background Since bone marrow receives innervation from A-delta and C-fibers and since an increase in intramedullary pressure in bone marrow may induce acute pain in orthopedic patients during surgery and chronic pain in patients with bone marrow edema, skeletal pain may partly originate from bone marrow. Intraosseous lesions, such as osteomyelitis and bone cancer, are also known to produce cutaneous hypersensitivity, which might be referred pain from bone. However, little is known about pain perception in bone marrow and referred pain induced by bone disease. Thus, we carried out an in vivo electrophysiological study and behavioral study to determine whether increased intraosseous pressure of the femur induces acute pain and whether increased intraosseous pressure induces referred pain in the corresponding receptive fields of the skin. Results Intraosseous balloon inflation caused spontaneous pain-related behavior and mechanical hyperalgesia and allodynia in the lumbosacral region. Single neuronal activities of spinal dorsal horn neurons were extracellularly isolated, and then evoked responses to non-noxious and noxious cutaneous stimuli and intraosseous balloon inflation were recorded. Ninety-four spinal dorsal horn neurons, which had somatic receptive fields at the lower back and thigh, were obtained. Sixty-two percent of the wide-dynamic-range neurons (24/39) and 86% of the high-threshold neurons (12/14) responded to intraosseous balloon inflation, while none of the low-threshold neurons (0/41) responded to intraosseous balloon inflation. Spinally administered morphine (1 µg) abolished balloon inflation-induced spontaneous pain-related behavior and mechanical hyperalgesia in awake rats and also suppressed evoked activities of wide-dynamic-range neurons to noxious cutaneous stimulation and intraosseous balloon inflation. Conclusions The results suggest that mechanical stimulation to bone marrow produces nociception, concomitantly producing its referred pain

  7. Concise Review: Bone Marrow Mononuclear Cells for the Treatment of Ischemic Syndromes: Medicinal Product or Cell Transplantation?

    PubMed Central

    Rico, Laura; Herrera, Concha

    2012-01-01

    In November of 2011, the Committee for Advanced Therapies (CAT) of the European Medicines Agency (EMA) published two scientific recommendations regarding the classification of autologous bone marrow-derived mononuclear cells (BM-MNCs) and autologous bone marrow-derived CD133+ cells as advanced therapy medicinal products (ATMPs), specifically tissue-engineered products, when intended for regeneration in ischemic heart tissue on the basis that they are not used for the same essential function (hematological restoration) that they fulfill in the donor. In vitro and in vivo evidence demonstrates that bone marrow cells are physiologically involved in adult neovascularization and tissue repair, making their therapeutic use for these purposes a simple exploitation of their own essential functions. Therefore, from a scientific/legal point of view, nonsubstantially manipulated BM-MNCs and CD133+ cells are not an ATMP, because they have a physiological role in the processes of postnatal neovascularization and, when used therapeutically for vascular restoration in ischemic tissues, they are carrying out one of their essential physiological functions (the legal definition recognizes that cells can have several essential functions). The consequences of classifying BM-MNCs and CD133+ cells as medicinal products instead of cellular transplantation, like bone marrow transplantation, in terms of costs and time for these products to be introduced into clinical practice, make this an issue of crucial importance. Therefore, the recommendations of EMA/CAT could be reviewed in collaboration with scientific societies, in light of organizational and economic consequences as well as scientific knowledge recently acquired about the mechanisms of postnatal neovascularization and the function of bone marrow in the regeneration of remote tissues. PMID:23197819

  8. Concise review: bone marrow mononuclear cells for the treatment of ischemic syndromes: medicinal product or cell transplantation?

    PubMed

    Cuende, Natividad; Rico, Laura; Herrera, Concha

    2012-05-01

    In November of 2011, the Committee for Advanced Therapies (CAT) of the European Medicines Agency (EMA) published two scientific recommendations regarding the classification of autologous bone marrow-derived mononuclear cells (BM-MNCs) and autologous bone marrow-derived CD133+ cells as advanced therapy medicinal products (ATMPs), specifically tissue-engineered products, when intended for regeneration in ischemic heart tissue on the basis that they are not used for the same essential function (hematological restoration) that they fulfill in the donor. In vitro and in vivo evidence demonstrates that bone marrow cells are physiologically involved in adult neovascularization and tissue repair, making their therapeutic use for these purposes a simple exploitation of their own essential functions. Therefore, from a scientific/legal point of view, nonsubstantially manipulated BM-MNCs and CD133+ cells are not an ATMP, because they have a physiological role in the processes of postnatal neovascularization and, when used therapeutically for vascular restoration in ischemic tissues, they are carrying out one of their essential physiological functions (the legal definition recognizes that cells can have several essential functions). The consequences of classifying BM-MNCs and CD133+ cells as medicinal products instead of cellular transplantation, like bone marrow transplantation, in terms of costs and time for these products to be introduced into clinical practice, make this an issue of crucial importance. Therefore, the recommendations of EMA/CAT could be reviewed in collaboration with scientific societies, in light of organizational and economic consequences as well as scientific knowledge recently acquired about the mechanisms of postnatal neovascularization and the function of bone marrow in the regeneration of remote tissues.

  9. Long-term survival of murine allogeneic bone marrow chimeras: effect of anti-lymphocyte serum and bone marrow dose

    SciTech Connect

    Norin, A.J.; Emeson, E.E.; Veith, F.J.

    1981-02-01

    Graft-vs-host disease (GVHD) and failure of donor stem cells to engraft permanently are two major obstacles to successful bone marrow transplantation. The effect of a single large dose of anti-lymphocyte serum (ALS) on mice receiving various numbers of H-2 incompatible bone marrow cells was evaluated. Most animals receiving lethal total body irradiation (TBI) and allogeneic marrow died within 45 days due to GVHD. Mice that were given ALS 6 to 24 h before TBI and bone marrow 24 h after irradiation survived in good health for more than 200 days. These cell preparations caused lethal GVHD in third party mice indicating that the lack of alloreactivity was specific to the strain in which the unresponsiveness was originally induced.

  10. Effects of Spaceflight on Cells of Bone Marrow Origin

    PubMed Central

    Özçivici, Engin

    2013-01-01

    Once only a subject for science fiction novels, plans for establishing habitation on space stations, the Moon, and distant planets now appear among the short-term goals of space agencies. This article reviews studies that present biomedical issues that appear to challenge humankind for long-term spaceflights. With particularly focus on cells of bone marrow origin, studies involving changes in bone, immune, and red blood cell populations and their functions due to extended weightlessness were reviewed. Furthermore, effects of mechanical disuse on primitive stem cells that reside in the bone marrow were also included in this review. Novel biomedical solutions using space biotechnology will be required in order to achieve the goal of space exploration without compromising the functions of bone marrow, as spaceflight appears to disrupt homeostasis for all given cell types. Conflict of interest:None declared. PMID:24385745

  11. Cell survival kinetics in peripheral blood and bone marrow during total body irradiation for marrow transplantation

    SciTech Connect

    Shank, B.; Andreeff, M.; Li, D.

    1983-11-01

    Cell survival kinetics in both peripheral blood and in bone marrow have been studied over the time course of hyperfractionated total body irradiation (TBI) for bone marrow transplantation. Our unique TBI regimen allows the study of the in vivo radiation effect uncomplicated by prior cyclophosphamide, since this agent is given after TBI in our cytoreduction scheme. Peripheral blood cell concentrations were monitored with conventional laboratory cell counts and differentials. Absolute bone marrow cell concentrations were monitored by measuring cell concentrations in an aspirate sample and correcting for dilution with blood by a cell cycle kinetic method using cytofluorometry. For lymphocytes in peripheral blood in patients in remission, the effective D/sub 0/ ranged from 373 rad in 10 children less than or equal to 10 y old, to 536 rad in the four patients between 11 to 17 y old, while n = 1.0 in all groups. There was no trend observed according to age. Granulocytes had a much higher effective D/sub 0/, approximately 1000 rad in vivo. Absolute nucleated cell concentration in marrow dropped slowly initially, due to an increased lymphocyte concentration in marrow during a concurrent drop in lymphocyte concentration in peripheral blood, but eventually fell on the last day of TBI ranging from 7 to 44% of the initial marrow nucleated cell concentration. Marrow myeloid elements, however, dropped continuously throughout the course of TBI.

  12. Usefulness of bone marrow imaging in childhood malignancies

    SciTech Connect

    Oseas, R.S.; Siddiqui, A.R.; Wellman, H.N.; Baehner, R.L.

    1982-08-01

    Two hundred six /sup 99m/Tc sulfur colloid bone marrow scans in 110 pediatrics patients were reviewed. The normal distribution of sulfur colloid in the lower extremities in various age groups was established. There was progressive loss of uptake with increasing age from less than two years to greater than ten years. Tumor replacement was seen as regions of decreased radioactivity, and the extent of the scan defect paralleled the response of the disease to therapy. Both chemotherapy and irradiation resulted in an extension of the /sup 99m/Tc SC to peripheral marrow sites. In irradiated areas, marrow scan defects were demonstrated and generally recovered normal activity by six months after the completion of therapy. Marrow scan abnormalities caused by tumor replacement were present in four patients despite normal bone scans and radiographs. Ultimate confirmation of tumor involvement was by needle aspiration or biopsy. Persistent marrow defects were seen in two patients with neuroblastoma who had remission of their disease: biopsy revealed myelofibrosis. /sup 99m/Tc sulfur colloid bone marrow scanning is a sensitive monitor of altered marrow activity associated with pediatric hematologic or oncologic diseases.

  13. Spatial mapping of functional pelvic bone marrow using FLT PET.

    PubMed

    McGuire, Sarah M; Menda, Yusuf; Boles Ponto, Laura L; Gross, Brandie; TenNapel, Mindi; Smith, Brian J; Bayouth, John E

    2014-07-08

    The purpose of this study was to determine the ability of regions identified with bony landmarks on CT imaging to accurately represent active bone marrow when compared to FLT PET imaging. These surrogate regions could then be used to create a bone marrow sparing radiation therapy plan when FLT PET imaging is not available. Whole body (WB) FLT PET images were obtained of 18 subjects prior to chemoradiation therapy. The FLT image of each subject was registered to a CT image acquired for that subject to obtain anatomic information of the pelvis. Seventeen regions were identified based on features of the pelvic bones, sacrum, and femoral heads. The probability of FLT uptake being located in each of 17 different CT-based regions of the bony pelvis was calculated using Tukey's multiple comparison test. Statistical analysis of FLT uptake in the pelvis indicated four distinct groups within the 17 regions that had similar levels of activity. Regions located in the central part of the pelvis, including the superior part of the sacrum, the inner halves of the iliac crests, and the L5 vertebral body, had greater FLT uptake than those in the peripheral regions (p-value < 0.05). We have developed a method to use CT-defined pelvic bone regions to represent FLT PET-identified functional bone marrow. Individual regions that have a statistically significant probability of containing functional bone marrow can be used as avoidance regions to reduce radiation dose to functional bone marrow in radiation therapy planning. However, because likely active bone marrow regions and pelvic targets typically overlap, patient-specific spatial detail may be advantageous in IMRT planning scenarios and may best be provided using FLT PET imaging.

  14. Bone marrow-derived mesenchymal stem cell plasticity and their application perspectives.

    PubMed

    Menabde, G; Gogilashvili, K; Kakabadze, Z; Berishvili, E

    2009-02-01

    The aim of this review is to summarize recent developments in research on the characteristics of bone marrow-derived mesenchymal stem cell plasticity. Stem cells are uncommitted entities capable of both self-renewal and differentiation into multiple cell lineages. In general, there are certain types of stem cell populations that are identified from embryonic and postnatal tissues. Embryonic stem cells are derived from mammalian blastocytes and theoretically have the ability to generate differentiated cell types arising from the three germ layers: mesoderm, ectoderm and endoderm. In contrast, postnatal stem cells are thought to be tissue specific, committed precursors capable of developing into a restricted number of cell lineages. Bone marrow stromal stem cells (BMSSCs), also known as mesenchymal stem cells, have been identified as a population of organized hierarchical postnatal stem cells with the potential to differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, myoblasts and neural cells. Recently, studies on the plasticity of BMSSCs challenge the traditional dogma that the differentiation and commitment of postnatal stem cells are limited to cell populations resident in their local environment. Current boneregenerative techniques, such as autologous bone grafting, allografts and alloplastic materials, have limitations that hinder their use in a wider range of clinical conditions. Hence, the development of improved methods, such as BMSSC-mediated bone regeneration, is necessary for achieving future viable therapeutic alternatives.

  15. Lasting engraftment of histoincompatible bone marrow cells in dogs

    SciTech Connect

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.C.; Zurcher, C.; van Bekkum, D.W.

    1981-05-01

    Conditioning protocols were tested for their efficacy in increasng the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradiation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-h interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplotype-mismatched donor. Possibilities for further improvement of this protocol are discussed.

  16. Lasting engraftment of histoincompatible bone marrow cells in dogs

    SciTech Connect

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.; Zurcher, C.; van Bekkum, D.W.

    1981-05-01

    Conditioning protocols were tested for their efficacy in increasing the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-hr interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplo-type-mismatched donor. Possibilities for further improvement of this protocol are discussed.

  17. Cells derived from young bone marrow alleviate renal aging.

    PubMed

    Yang, Hai-Chun; Rossini, Michele; Ma, Li-Jun; Zuo, Yiqin; Ma, Ji; Fogo, Agnes B

    2011-11-01

    Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.

  18. Hematopoietic bone marrow recovery after radiation therapy: MRI evaluation

    SciTech Connect

    Casamassima, F.; Ruggiero, C.; Caramella, D.; Tinacci, E.; Villari, N.; Ruggiero, M. )

    1989-05-01

    Magnetic resonance imaging (MRI) is able to detect the increase of adipocytes in the hematopoietic bone marrow that occurs as a consequence of radiotherapy and is indicative of the loss of myeloid tissue. By monitoring this process, it is also possible to determine the recovery of the bone marrow. The amount of viable hematopoietic tissue plays a fundamental role in determining whether the patient is able to undergo further antineoplastic therapy, particularly chemotherapy. We examined 35 patients who had been treated with radiotherapy for Hodgkin's lymphoma (12), uterine cervix carcinoma (nine), ovarian dysgerminoma (six), testicular seminoma (four), and non-Hodgkin's lymphoma (four). We observed that radiation-induced modifications of the MRI pattern in the bone marrow are tightly linked to two parameters; the administered radiation dose and the length of time passed after the treatment. Bone marrow recovery was observed only when patients were treated with doses lower than 50 Gy. The earlier radiation-induced modifications of the bone marrow MRI pattern occurred 6 to 12 months after irradiation, and they were most evident 5 to 6 years after the treatment. From 2 to 9 years after radiotherapy, we observed partial recovery. Complete recovery, when it occurred, was observed only 10 to 23 years after the treatment. Our results indicate that MRI studies are likely to be useful in the assessment of radiation-induced injuries.

  19. Spine fusion using cell matrix composites enriched in bone marrow-derived cells.

    PubMed

    Muschler, George F; Nitto, Hironori; Matsukura, Yoichi; Boehm, Cynthia; Valdevit, Antonio; Kambic, Helen; Davros, William; Powell, Kimerly; Easley, Kirk

    2003-02-01

    Bone marrow-derived cells including osteoblastic progenitors can be concentrated rapidly from bone marrow aspirates using the surface of selected implantable matrices for selective cell attachment. Concentration of cells in this way to produce an enriched cellular composite graft improves graft efficacy. The current study was designed to test the hypothesis that the biologic milieu of a bone marrow clot will significantly improve the efficacy of such a graft. An established posterior spinal fusion model and cancellous bone matrix was used to compare an enriched cellular composite bone graft alone, bone matrix plus bone marrow clot, and an enriched bone matrix composite graft plus bone marrow clot. Union score, quantitative computed tomography, and mechanical testing were used to define outcome. The union score for the enriched bone matrix plus bone marrow clot composite was superior to the enriched bone matrix alone and the bone matrix plus bone marrow clot. The enriched bone matrix plus bone marrow clot composite also was superior to the enriched bone matrix alone in fusion volume and in fusion area. These data confirm that the addition of a bone marrow clot to an enriched cell-matrix composite graft results in significant improvement in graft performance. Enriched composite grafts prepared using this strategy provide a rapid, simple, safe, and inexpensive method for intraoperative concentration and delivery of bone marrow-derived cells and connective tissue progenitors that may improve the outcome of bone grafting.

  20. Bone marrow endothelium-targeted therapeutics for metastatic breast cancer.

    PubMed

    Mai, Junhua; Huang, Yi; Mu, Chaofeng; Zhang, Guodong; Xu, Rong; Guo, Xiaojing; Xia, Xiaojun; Volk, David E; Lokesh, Ganesh L; Thiviyanathan, Varatharasa; Gorenstein, David G; Liu, Xuewu; Ferrari, Mauro; Shen, Haifa

    2014-08-10

    Effective treatment of cancer metastasis to the bone relies on bone marrow drug accumulation. The surface proteins in the bone marrow vascular endothelium provide docking sites for targeted drug delivery. We have developed a thioaptamer that specifically binds to E-selectin that is overexpressed in the vasculature of tumor and inflammatory tissues. In this study, we tested targeted delivery of therapeutic siRNA loaded in the E-selectin thioaptamer-conjugated multistage vector (ESTA-MSV) drug carrier to bone marrow for the treatment of breast cancer bone metastasis. We evaluated tumor type- and tumor growth stage-dependent targeting in mice bearing metastatic breast cancer in the bone, and carried out studies to identify factors that determine targeting efficiency. In a subsequent study, we delivered siRNA to knock down expression of the human STAT3 gene in murine xenograft models of human MDA-MB-231 breast tumor, and assessed therapeutic efficacy. Our studies revealed that the CD31(+)E-selectin(+) population accounted for 20.8%, 26.4% and 29.9% of total endothelial cells respectively inside the femur of mice bearing early, middle and late stage metastatic MDA-MB-231 tumors. In comparison, the double positive cells remained at a basal level in mice with early stage MCF-7 tumors, and jumped to 23.9% and 28.2% when tumor growth progressed to middle and late stages. Accumulation of ESTA-MSV inside the bone marrow correlated with the E-selectin expression pattern. There was up to 5-fold enrichment of the targeted MSV in the bone marrow of mice bearing early or late stage MDA-MB-231 tumors and of mice with late stage, but not early stage, MCF-7 tumors. Targeted delivery of STAT3 siRNA in ESTA-MSV resulted in knockdown of STAT3 expression in 48.7% of cancer cells inside the bone marrow. Weekly systemic administration of ESTA-MSV/STAT3 siRNA significantly extended survival of mice with MDA-MB-231 bone metastasis. In conclusion, targeting the overexpressed E

  1. Platelet lysate favours in vitro expansion of human bone marrow stromal cells for bone and cartilage engineering.

    PubMed

    Zaky, S H; Ottonello, A; Strada, P; Cancedda, R; Mastrogiacomo, M

    2008-12-01

    The heterogeneous population of non-haematopoietic cells residing in the bone marrow (bone marrow stromal cells, BMSCs) and the different fractions and components obtained from platelet-rich plasma provide an invaluable source of autologous cells and growth factors for bone and other connective tissue reconstruction. In this study, we investigated the effect of an allogenic platelet lysate on human BMSCs proliferation and differentiation. Cell proliferation and number of performed cell doublings were enhanced in cultures supplemented with the platelet-derived growth factors (platelet lysate, PL), either with or without the concomitant addition of fetal bovine serum (FBS), compared to cultures performed in the presence of FBS and FGF2. Both in vitro and in vivo osteogenic differentiation were unaltered in cells maintained in medium supplemented with PL and not FBS (Only PL) and in cells maintained in medium containing FBS and FGF2. Interestingly, the in vitro cartilage formation was more effective in the pellet of BMSCs expanded in the Only PL medium. In particular, a chondrogenic differentiation was observed in pellets of some in vitro-expanded BMSCs in the Only PL medium, whereas pellets from parallel cell cultures in medium containing FBS did not respond to the chondrogenic induction. We conclude that the platelet lysate from human source is an effective and even more beneficial substitute for fetal bovine serum to support the in vitro expansion of human BMSCs for subsequent tissue-engineering applications.

  2. Total Marrow Irradiation as Part of Autologous Stem Cell Transplantation for Asian Patients with Multiple Myeloma

    PubMed Central

    Lin, Shih-Chiang; Hsieh, Pei-Ying; Shueng, Pei-Wei; Tien, Hui-Ju; Wang, Li-Ying

    2013-01-01

    To compare the outcomes of melphalan 200 mg/m2 (HDM200) and 8 Gy total marrow irradiation (TMI) delivered by helical tomotherapy plus melphalan 140 mg/m2 (HDM140 + TMI 8 Gy) in newly diagnosed symptomatic multiple myeloma (MM) Asian patients. Between 2007 and 2010, nine consecutive myeloma patients who were scheduled to undergo autologous stem cell transplantation (ASCT) were studied. The patients received three cycles of vincristine-adriamycin-dexamethasone (VAD) regimen as induction chemotherapy, and if they had a partial response, peripheral blood stem cells were collected by dexamethasone-etoposide-cyclophosphamide-cisplatin (DECP). In arm A, six patients received the HDM200. In arm B, three patients received HDM140 + TMI 8 Gy. In arm B, the neutropenic duration was slightly longer than in arm A (P = 0.048). However, hematologic recovery (except for neutrophils), transfusion requirement, median duration of hospitalization, and the dose of G-CSF were similar in both arms. The median duration of overall survival and event-free survival was similar in the two arms (P = 0.387). As a conditioning regiment, HDM140 + TMI 8 Gy provide another chance for MM Asian patients who were not feasible for HDM200. PMID:24089671

  3. Composite vascularized skin/bone transplantation models for bone marrow-based tolerance studies.

    PubMed

    Ozmen, Selahattin; Ulusal, Betul G; Ulusal, Ali E; Izycki, Dariusz; Siemionow, Maria

    2006-03-01

    There is an ongoing need to understand the mechanisms of bone marrow-based allograft tolerance. This is important in clarifying the diverse variables influencing the ultimate outcome of the solid organ and composite tissue transplants. To establish bone marrow transplantation as a routine clinical application, further experimental studies should be conducted to overcome the obstacles related to the bone marrow transplantation. These obstacles include graft versus host disease, immunocompetence, and toxicity of the conditioning regimens. For these purposes, novel experimental models are needed. In an attempt to provide a reliable research tool for bone marrow-based tolerance induction studies, we introduced different experimental models of modified vascularized skin/bone marrow (VSBM) transplantation technique for tolerance induction, monitoring, and maintenance studies. In this skin/bone transplantation model, the technical feasibility of concurrent or consecutive transplantation of the combination of bilateral vascularized skin, vascularized bone marrow, or vascularized skin/bone marrow transplants was investigated. Isograft transplantations were performed between genetically identical Lewis (LEW, RT1) rats. Five different experimental designs in 5 groups of 5 animals each were studied. Group I: Bilateral vascularized skin (VS) transplantation; group II: bilateral vascularized skin/bone transplantation; group III: vascularized skin transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group IV: vascularized bone transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group V: vascularized bone transplantation on one side and vascularized skin transplantation on the contralateral side. Successful transplantations were performed in all groups. The survival of the isograft transplants was evaluated clinically and histologically. All skin flaps remained pink and pliable and grew new

  4. Mechanical stimulation of bone marrow in situ induces bone formation in trabecular explants.

    PubMed

    Birmingham, E; Kreipke, T C; Dolan, E B; Coughlin, T R; Owens, P; McNamara, L M; Niebur, G L; McHugh, P E

    2015-04-01

    Low magnitude high frequency (LMHF) loading has been shown to have an anabolic effect on trabecular bone in vivo. However, the precise mechanical signal imposed on the bone marrow cells by LMHF loading, which induces a cellular response, remains unclear. This study investigates the influence of LMHF loading, applied using a custom designed bioreactor, on bone adaptation in an explanted trabecular bone model, which isolated the bone and marrow. Bone adaptation was investigated by performing micro CT scans pre and post experimental LMHF loading, using image registration techniques. Computational fluids dynamic models were generated using the pre-experiment scans to characterise the mechanical stimuli imposed by the loading regime prior to adaptation. Results here demonstrate a significant increase in bone formation in the LMHF loaded group compared to static controls and media flow groups. The calculated shear stress in the marrow was between 0.575 and 0.7 Pa, which is within the range of stimuli known to induce osteogenesis by bone marrow mesenchymal stem cells in vitro. Interestingly, a correlation was found between the bone formation balance (bone formation/resorption), trabecular number, trabecular spacing, mineral resorption rate, bone resorption rate and mean shear stresses. The results of this study suggest that the magnitude of the shear stresses generated due to LMHF loading in the explanted bone cores has a contributory role in the formation of trabecular bone and improvement in bone architecture parameters.

  5. Cell Fate and Differentiation of Bone Marrow Mesenchymal Stem Cells

    PubMed Central

    Jimi, Eijiro

    2016-01-01

    Osteoblasts and bone marrow adipocytes originate from bone marrow mesenchymal stem cells (BMMSCs) and there appears to be a reciprocal relationship between adipogenesis and osteoblastogenesis. Alterations in the balance between adipogenesis and osteoblastogenesis in BMMSCs wherein adipogenesis is increased relative to osteoblastogenesis are associated with decreased bone quality and quantity. Several proteins have been reported to regulate this reciprocal relationship but the exact nature of the signals regulating the balance between osteoblast and adipocyte formation within the bone marrow space remains to be determined. In this review, we focus on the role of Transducin-Like Enhancer of Split 3 (TLE3), which was recently reported to regulate the balance between osteoblast and adipocyte formation from BMMSCs. We also discuss evidence implicating canonical Wnt signalling, which plays important roles in both adipogenesis and osteoblastogenesis, in regulating TLE3 expression. Currently, there is demand for new effective therapies that target the stimulation of osteoblast differentiation to enhance bone formation. We speculate that reducing TLE3 expression or activity in BMMSCs could be a useful approach towards increasing osteoblast numbers and reducing adipogenesis in the bone marrow environment. PMID:27298623

  6. Promising cell-based therapy for bone regeneration using stem cells from deciduous teeth, dental pulp, and bone marrow.

    PubMed

    Yamada, Yoichi; Ito, Kenji; Nakamura, Sayaka; Ueda, Minoru; Nagasaka, Tetsuro

    2011-01-01

    We attempted to regenerate bone in a significant osseous defect with various stem cells from deciduous teeth, extracted from puppies, and grafted them into a parent canine mandible as an allograft, parent dental pulp, and bone marrow by tissue engineering and regenerative medicine technology using platelet-rich plasma as an autologous scaffold and signal molecules. Initially, teeth were extracted from a child and parent hybrid canine mandible region and bone marrow (canine mesenchymal stem cells; cMSCs), and parent teeth (canine dental pulp stem cells; cDPSCs), and stem cells were extracted from deciduous teeth (puppy deciduous teeth stem cells; pDTSCs). After 4 weeks, bone defects were prepared on both sides of the mandible with a trephine bar. Graft materials were implanted into these defects: 1) control (defect only), 2) platelet-rich plasma (PRP), 3) cMSCs/PRP, 4) cDPSCs/PRP, and 5) pDTSCs/PRP to investigate the effect of stem cells. The newly formed bones were evaluated by histology and histomorphometric analysis in the defects at 2, 4, and 8 weeks. According to histological observations, the cMSCs/PRP, cDPSCs/PRP, and pDTSCs/PRP groups had well-formed mature bone and neovascularization compared with the control (defect only) and PRP groups at 4 and 8 weeks, respectively, and the mineralized tissues in cMSCs/PRP, cDPSCs/PRP, and pDTSCs/PRP specimens were positive for osteocalcin at 8 weeks. Histometrically, newly formed bone areas were 19.0 ± 2.9% (control), 19.7 ± 6.0% (PRP), 52.8 ± 3.5% (cMSCs/PRP), 61.6 ± 1.3% (cDPSCs/PRP), and 54.7 ± 2.2% (pDTSCs/PRP) at 8 weeks. There were significant differences between cMSCs, cDPSCs, pDTSCs/PRP, and control and PRP groups. These results demonstrate that stem cells from deciduous teeth, dental pulp, and bone marrow with PRP have the ability to form bone, and bone formation with DTSCs might have the potential to generate a graft between a child and parent. This preclinical study could pave the way for stem cell

  7. Qualitative Aspects of Bone Marrow Adiposity in Osteoporosis

    PubMed Central

    Pino, Ana María; Miranda, Melissa; Figueroa, Carolina; Rodríguez, Juan Pablo; Rosen, Clifford J.

    2016-01-01

    The function of marrow adipocytes and their origin has not been defined although considerable research has centered on their presence in certain conditions, such as osteoporosis. Less work has focused on the qualitative aspects of marrow fat. Bone marrow serum is composed of multiple nutrients that almost certainly relate to functional aspects of the niche. Previous studies using non-invasive techniques have shown that osteoporotic individuals have more marrow fat and that the ratio of saturated: unsaturated fatty acid is high. We recently reported that bone marrow sera from osteoporotic patients with fracture showed a switch toward decreased content of total saturated versus unsaturated fatty acids, compared to patients without fracture highlighting a dynamic relationship between the composition of fatty acids in the bone microenvironment and the metabolic requirements of cells. The relative distribution of fatty acids differed considerably from that in the serum providing further evidence that energy utilization is high and that marrow adipocytes may contribute to this pool. Whether these lipids can affect osteoblast function in a positive or negative manner is still not certain but will require further investigation. PMID:27826285

  8. Modeling selective elimination of quiescent cancer cells from bone marrow.

    PubMed

    Cavnar, Stephen P; Rickelmann, Andrew D; Meguiar, Kaille F; Xiao, Annie; Dosch, Joseph; Leung, Brendan M; Cai Lesher-Perez, Sasha; Chitta, Shashank; Luker, Kathryn E; Takayama, Shuichi; Luker, Gary D

    2015-08-01

    Patients with many types of malignancy commonly harbor quiescent disseminated tumor cells in bone marrow. These cells frequently resist chemotherapy and may persist for years before proliferating as recurrent metastases. To test for compounds that eliminate quiescent cancer cells, we established a new 384-well 3D spheroid model in which small numbers of cancer cells reversibly arrest in G1/G0 phase of the cell cycle when cultured with bone marrow stromal cells. Using dual-color bioluminescence imaging to selectively quantify viability of cancer and stromal cells in the same spheroid, we identified single compounds and combination treatments that preferentially eliminated quiescent breast cancer cells but not stromal cells. A treatment combination effective against malignant cells in spheroids also eliminated breast cancer cells from bone marrow in a mouse xenograft model. This research establishes a novel screening platform for therapies that selectively target quiescent tumor cells, facilitating identification of new drugs to prevent recurrent cancer.

  9. Whole bone marrow irradiation for the treatment of multiple myeloma

    SciTech Connect

    Coleman, M.; Saletan, S.; Wolf, D.; Nisce, L.; Wasser, J.; McIntyre, O.R.; Tulloh, M.

    1982-04-01

    Nine patients with multiple myeloma were treated with whole bone marrow irradiation. Six had heavily pretreated disease refractory to chemotherapy. Three had stable disease lightly pretreated by chemotherapy. A modification of the ''three and two'' total nodal radiation technique was employed. Although varying and often severe treatment related cytopenia occurred, infectious complications, clinical bleeding, and nonhematalogic complications were minimal. Five of nine patients showed a decrease in monoclonal protein components, and one showed an increase during treatment. These preliminary results indicate that a reduction of tumor cell burden may occur in patients following whole bone marrow irradiation and that the technique is feasible. Whole bone marrow irradiation combined with chemotherapy represents a new conceptual therapeutic approach for multiple myeloma.

  10. Risk factors in interstitial pneumonitis following allogenic bone marrow transplantation

    SciTech Connect

    Pino Y Torres, J.L.; Bross, D.S.; Lam, W.C.; Wharam, M.D.; Santos, G.W.; Order, S.E.

    1982-08-01

    Total body irradiation is part of the preparatory regimen for allogeneic bone marrow transplantation because of its cytotoxic and immunosuppressive properties. A major toxicity of bone marrow transplantation has been interstitial pneumonitis, which may be, in part, related to the lung irradiation. One hundred and sixty-one consecutive patients receiving allogeneic bone marrow transplantation for leukemia and aplastic anemia at Johns Hopkins Hospital (1968-1979) were retrospectively studied. The present study demonstrated that lung shielding to 600 rad maximum in single dose total body irradiation, fractionation of total body irradiation in comparison to single dose total body irradiation, and absence of graft versus host disease in the leukemia patients, each reduced the risk of interstitial pneumonitis. Total body irradiation significantly reduced the leukemia recurrence rate and/or the failure of remission induction.

  11. Limiting-dilution analysis for the determination of leukemic cell frequencies after bone marrow decontamination with mafosfamide or merocyanine 540

    SciTech Connect

    Porcellini, A.; Talevi, N.; Marchetti-Rossi, M.T.; Palazzi, M.; Manna, A.; Sparaventi, G.; Delfini, C.; Valentini, M.

    1987-11-01

    To stimulate a leukemia remission marrow, cell suspensions of normal human bone marrow were mixed with human acute lymphoblastic or myelogenous leukemic cells of the CCRF-SF, Nalm-6, and K-562 lines. The cell mixtures were incubated in vitro with mafosfamide (AZ) or with the photoreactive dye merocyanine 540 (MC-540). A quantity of 10(4) cells of the treated suspensions was dispensed into microculture plates, and graded cell numbers of the line used to contaminate the normal marrow were added. Limiting-dilution analysis was used to estimate the frequency of leukemia cells persisting after treatment with the decontaminating agents. Treatment with AZ or MC-540 produced a total elimination (ie, 6 logs or 5.3 logs respectively) of B cell acute leukemia cells (CCRF-SB), whereas nearly 1.7 logs and 2 logs of K-562 acute myelogenous blasts were still present in the cell mixtures after treatment with MC-540 and AZ, respectively. Treatment of the Nalm-6-contaminated cell mixtures with AZ resulted in 100% elimination of clonogenic cells, whereas nearly 80% decontamination was obtained with MC-540. Our results suggest that treatment with AZ could be an effective method of eliminating clonogenic tumor cells from human bone marrow. MC-540, shown by previous studies to spare sufficient pluripotential stem cells to ensure hemopoietic reconstitution in the murine model and in clinical application, has comparable effects and merits trials for possible clinical use in autologous bone marrow transplantation.

  12. Genotoxicity of ibuprofen in mouse bone marrow cells in vivo.

    PubMed

    Tripathi, Rina; Pancholi, Shyam S; Tripathi, Pankaj

    2012-10-01

    Genotoxicity of ibuprofen was evaluated by employing the mouse in vivo chromosomal aberration (CA) test. Ibuprofen administered orally at doses of 10, 20, 40, and 60 mg/kg body weight to mice resulted in mitotic depression and induction of CAs. A dose-related decrease in mitotic index (MI) and an increase in the frequencies of chromosomal aberrations per cell (CAs/cell) were recorded in bone marrow cells. However, a statistically significant reduction in MI and an increase in CAs/cell were found for both the higher doses. The results obtained indicate that ibuprofen is capable of inducing dose-dependent genotoxicity in bone marrow cells of mice.

  13. Systemic bone marrow disorders: Characterization with proton chemical shift imaging

    SciTech Connect

    Gueckel, F.B.; Brix, G.; Semmler, W.; Zuna, I.; Knauf, W.; Ho, A.D.; van Kaick, G. )

    1990-07-01

    In a prospective clinical study, 26 patients (22 with malignant lymphoma and 4 with myelofibrosis) and 9 healthy volunteers were examined by conventional magnetic resonance and proton chemical shift imaging (CSI; modified Dixon method). On the basis of the CSI data, a quantitative evaluation of the relative fat and water signal fractions in regions of interest of the femur, pelvis, and spine was performed. In 16 of 17 patients with biopsy-proven bone marrow disorders, CSI revealed a significant reduction in the fat fraction of the bone marrow relative to that of normal volunteers. The visual assessment could detect only 14 of the 17 pathological cases.

  14. 18F-FDG super bone marrow uptake

    PubMed Central

    Alam, Mohammed Shah; Fu, Lilan; Ren, Yun-Yan; Wu, Hu-Bing; Wang, Quan-Shi; Han, Yan-Jiang; Zhou, Wen-Lan; Li, Hong-Sheng; Wang, Zhen

    2016-01-01

    Abstract The present study was performed to investigate whether the markedly 2-deoxy-2-(fluorine-18) fluoro-D-glucose (18F-FDG) uptake in the bone marrow (BM) is a presentation of malignant infiltration (MI). Super bone marrow uptake (super BMU) was used to name the markedly 18F-FDG uptake on BM, which was similar to or higher than that of the brain. From April 2008 to December 2015, 31 patients with such presentation were retrospectively reviewed. The 18F-FDG uptake was semiquantified using SUVmax and BM to cerebellum (BM/C) ratio. The origin of super BMU was diagnosed by pathology. Some blood parameters, as well as fever, were also collected and analyzed. For comparison, 106 patients with mildly and moderately uptake in BM and 20 healthy subjects were selected as the control group. Bone marrow MI was diagnosed in 93.5% (29/31) patients with super BMU, which mostly originated from acute leukemia and highly aggressive lymphoma. The super BMU group had markedly higher 18F-FDG uptake in the BM than those of mildly and moderately uptake, and the control subjects (all P = 0.000) and the BM/C ratio reached a high of 1.24 ± 0.36. The incidence of bone marrow MI in the super BMU group was markedly higher than that of mildly and moderately uptake (93.5% vs 36.8%, P = 0.000). Based on the receiver operating characteristic analysis, when cut-off values of BM/C and SUVmax were set at 0.835 and 6.560, the diagnostic specificity for bone marrow MI reached the high levels of 91.4% and 95.7%, respectively. In 15 patients with bone marrow MI, the extra-BM malignant lesions were simultaneously detected by 18F-FDG PET/CT. The liver and the nasal cavity involvements were only found in the patients with lymphoma, but not in those with leukemia. A decrease of leukocyte, hemoglobin, and platelet counts was noted in 48.4%, 86.2%, and 51.5% of patients with bone marrow MI, respectively. The present study revealed that super BMU was a highly potent indicator for the bone

  15. Consequences of irradiation on bone and marrow phenotypes, and its relation to disruption of hematopoietic precursors

    PubMed Central

    Green, Danielle E.; Rubin, Clinton T.

    2014-01-01

    The rising levels of radiation exposure, specifically for medical treatments and accidental exposures, have added great concern for the long term risks of bone fractures. Both the bone marrow and bone architecture are devastated following radiation exposure. Even sub-lethal doses cause a deficit to the bone marrow microenvironment, including a decline in hematopoietic cells, and this deficit occurs in a dose dependent fashion. Certain cell phenotypes though are more susceptible to radiation damage, with mesenchymal stem cells being more resilient than the hematopoietic stem cells. The decline in total bone marrow hematopoietic cells is accompanied with elevated adipocytes into the marrow cavity, thereby inhibiting hematopoiesis and recovery of the bone marrow microenvironment. Poor bone marrow is also associated with a decline in bone architectural quality. Therefore, the ability to maintain the bone marrow microenvironment would hinder much of the trabecular bone loss caused by radiation exposure, ultimately decreasing some comorbidities in patients exposed to radiation. PMID:24607941

  16. Bone marrow chimera experiments to determine the contribution of hematopoietic stem cells to cerebral angiogenesis.

    PubMed

    Machein, Marcia Regina; Plate, Karl H

    2014-01-01

    The generation of bone marrow chimera in mice is a valuable tool to study a variety of cellular processes. Donor bone marrow cells expressing reporter genes have been used to study the process of cell differentiation and the mechanisms involved in bone marrow cell recruitment. Bone marrow cells bearing genetic manipulation have been used in bone marrow chimeras to elucidate the role of molecules in different physiological and pathological settings. Since in the normal adult brain angiogenesis does not occur, models of brain injury like ischemia and tumor growth have been used to study the contribution of bone marrow-derived cells to the cerebral vasculature. This chapter describes the procedures to perform bone marrow transplantation in order to study the contribution of bone marrow-derived cells to vascularization in an orthotopic glioma model.

  17. Hematopoietic Stem Cells in Neural-crest Derived Bone Marrow

    PubMed Central

    Jiang, Nan; Chen, Mo; Yang, Guodong; Xiang, Lusai; He, Ling; Hei, Thomas K.; Chotkowski, Gregory; Tarnow, Dennis P.; Finkel, Myron; Ding, Lei; Zhou, Yanheng; Mao, Jeremy J.

    2016-01-01

    Hematopoietic stem cells (HSCs) in the endosteum of mesoderm-derived appendicular bones have been extensively studied. Neural crest-derived bones differ from appendicular bones in developmental origin, mode of bone formation and pathological bone resorption. Whether neural crest-derived bones harbor HSCs is elusive. Here, we discovered HSC-like cells in postnatal murine mandible, and benchmarked them with donor-matched, mesoderm-derived femur/tibia HSCs, including clonogenic assay and long-term culture. Mandibular CD34 negative, LSK cells proliferated similarly to appendicular HSCs, and differentiated into all hematopoietic lineages. Mandibular HSCs showed a consistent deficiency in lymphoid differentiation, including significantly fewer CD229 + fractions, PreProB, ProB, PreB and B220 + slgM cells. Remarkably, mandibular HSCs reconstituted irradiated hematopoietic bone marrow in vivo, just as appendicular HSCs. Genomic profiling of osteoblasts from mandibular and femur/tibia bone marrow revealed deficiencies in several HSC niche regulators among mandibular osteoblasts including Cxcl12. Neural crest derived bone harbors HSCs that function similarly to appendicular HSCs but are deficient in the lymphoid lineage. Thus, lymphoid deficiency of mandibular HSCs may be accounted by putative niche regulating genes. HSCs in craniofacial bones have functional implications in homeostasis, osteoclastogenesis, immune functions, tumor metastasis and infections such as osteonecrosis of the jaw. PMID:28000662

  18. Impaired Function of Bone Marrow Stromal Cells in Systemic Mastocytosis

    PubMed Central

    Nemeth, K.; Wilson, T.M.; Ren, J.J.; Sabatino, M.; Stroncek, D.F.; Krepuska, M.; Bai, Y.; Robey, P.G.; Metcalfe, D.D.; Mezey, E.

    2015-01-01

    Patients with systemic mastocytosis (SM) have a wide variety of problems, including skeletal abnormalities. The disease results from a mutation of the stem cell receptor (c-kit) in mast cells and we wondered if the function of bone marrow stromal cells (BMSCs; also known as MSCs or mesenchymal stem cells) might be affected by the invasion of bone marrow by mutant mast cells. As expected, BMSCs from SM patients do not have a mutation in c-kit, but they proliferate poorly. In addition, while osteogenic differentiation of the BMSCs seems to be deficient, their adipogenic potential appears to be increased. Since the hematopoietic supportive abilities of BMSCs are also important, we also studied the engraftment in NSG mice of human CD34+ hematopoietic progenitors, after being co-cultured with BMSCs of healthy volunteers vs. BMSCs derived from patients with SM. BMSCs derived from the bone marrow of patients with SM could not support hematopoiesis to the extent that healthy BMSCs do. Finally, we performed an expression analysis and found significant differences between healthy and SM derived BMSCs in the expression of genes with a variety of functions, including the WNT signaling, ossification, and bone remodeling. We suggest that some of the symptoms associated with SM might be driven by epigenetic changes in BMSCs caused by dysfunctional mast cells in the bone marrow of the patients. PMID:26001169

  19. Growth Hormone Regulates the Balance Between Bone Formation and Bone Marrow Adiposity

    PubMed Central

    Menagh, Philip J; Turner, Russell T; Jump, Donald B; Wong, Carmen P; Lowry, Malcolm B; Yakar, Shoshana; Rosen, Clifford J; Iwaniec, Urszula T

    2010-01-01

    Cancellous bone decreases and bone marrow fat content increases with age. Osteoblasts and adipocytes are derived from a common precursor, and growth hormone (GH), a key hormone in integration of energy metabolism, regulates the differentiation and function of both cell lineages. Since an age-related decline in GH is associated with bone loss, we investigated the relationship between GH and bone marrow adiposity in hypophysectomized (HYPOX) rats and in mice with defects in GH signaling. HYPOX dramatically reduced body weight gain, bone growth and mineralizing perimeter, serum insulin-like growth factor 1 (IGF-1) levels, and mRNA levels for IGF-1 in liver and bone. Despite reduced body mass and adipocyte precursor pool size, HYPOX resulted in a dramatic increase in bone lipid levels, as reflected by increased bone marrow adiposity and bone triglyceride and cholesterol content. GH replacement normalized bone marrow adiposity and precursor pool size, as well as mineralizing perimeter in HYPOX rats. In contrast, 17β -estradiol, IGF-1, thyroxine, and cortisone were ineffective. Parathyroid hormone (PTH) reversed the inhibitory effects of HYPOX on mineralizing perimeter but had no effect on adiposity. Finally, bone marrow adiposity was increased in mice deficient in GH and IGF-1 but not in mice deficient in serum IGF-1. Taken together, our findings indicate that the reciprocal changes in bone and fat mass in GH signaling-deficient rodents are not directly coupled with one another. Rather, GH enhances adipocyte as well as osteoblast precursor pool size. However, GH increases osteoblast differentiation while suppressing bone marrow lipid accumulation. © 2010 American Society for Bone and Mineral Research PMID:19821771

  20. Autologous transplantation in poor risk Hodgkin's disease using high dose melphalan/etoposide conditioning with non-cryopreserved marrow rescue. The Newcastle and Northern Region Lymphoma Group.

    PubMed Central

    Taylor, P. R.; Jackson, G. H.; Lennard, A. L.; Lucraft, H.; Proctor, S. J.

    1993-01-01

    This study aimed to assess the safety and efficacy of using high dose melphalan and etoposide followed by autologous, non-cryopreserved marrow rescue in advanced Hodgkin's disease (HD). Seventeen patients with poor risk Hodgkin's disease from a single centre underwent autologous bone marrow transplant (ABMT) using high dose melphalan and etopside conditioning. Two patients had primary progressive resistant disease (PD), two were in fourth relapse, six in second or third complete remission (CR), one patient had good partial response (GPR) (> 75% reduction in initial bulk) to primary therapy and six were in first complete remission. The patients transplanted in first CR all has a Scotland and Newcastle Lymphoma Group (SNLG) Prognostic Index (Proctor et al., 1991) which indicated they were in a poor risk prognostic group. Melphalan and etoposide both have a short half life enabling ABMT to be accomplished using unmanipulated marrow stored at 4 degrees C. The marrow was returned to the patient within 56 h of harvest. Complete haematological reconstitution occurred in 16/17 patients, the rate of engraftment reflecting the amount of previous chemotherapy. One patient died of progressive Hodgkin's disease before full engraftment could occur. In patients autografted in first remission, the median number of days with neutropenia (< 0.5 x 10(9) l-1 neutrophils) was 19 (range 9-33) and, in those in subsequent remission, 27 days (range 18-36). The median number of days to 50 x 10(9) l-1 platelets in the same groups were 29 (21-80) and 50 (41-74) respectively. The number of days in hospital post transplant in both groups was similar; median 22 (15-27) and 23 (17-37) respectively. There were no procedural deaths and none of the patients transplanted in first, second or third CR have relapsed (median follow up 21 months). The two patients transplanted with progressive disease showed only temporary responses. The two patients transplanted in fourth relapse went into CR; one is

  1. Regulation of vitamin C transporter in the type 1 diabetic mouse bone and bone marrow.

    PubMed

    Sangani, Rajnikumar; Naime, Mohammad; Zakhary, Ibrahim; Ahmad, Saif; Chutkan, Norman; Zhu, Andy; Ha, Yonju; Hamrick, Mark; Isales, Carlos; Elsalanty, Mohammed; Smith, Sylvia; Liou, Gregory I; Fulzele, Sadanand

    2013-12-01

    A number of studies have revealed that Type I diabetes (T1D) is associated with bone loss and an increased risk of fractures. T1D induces oxidative stress in various tissues and organs. Vitamin C plays an important role in the attenuation of oxidative stress; however, little is known about the effect of T1D induced oxidative stress on the regulation of vitamin C transporter in bone and bone marrow cells. To investigate this, T1D was induced in mice by multiple low dose injections of streptozotocin. We have demonstrated that endogenous antioxidants, glutathione peroxidase (GPx) and superoxide dismutase (SOD) are down-regulated in the bone and bone marrow of T1D. The vitamin C transporter isoform SVCT2, the only known transporter expressed in bone and bone marrow stromal cells (BMSCs), is negatively regulated in the bone and bone marrow of T1D. The μCT imaging of the bone showed significantly lower bone quality in the 8 week T1D mouse. The in-vitro study in BMSCS showed that the knockdown of SVCT2 transporter decreases ascorbic acid (AA) uptake, and increases oxidative stress. The significant reversing effect of antioxidant vitamin C is only possible in control cells, not in knockdown cells. This study suggested that T1D induces oxidative stress and decreases SVCT2 expression in the bone and bone marrow environment. Furthermore, this study confirms that T1D increases bone resorption, decreases bone formation and changes the microstructure of bones. This study has provided evidence that the regulation of the SVCT2 transporter plays an important role not only in T1D osteoporosis but also in other oxidative stress-related musculoskeletal complications.

  2. HLA Typing for Bone Marrow Transplantation

    DTIC Science & Technology

    2007-10-31

    storage of the first product at the apheresis center. It is also common, particularly if products arrive late in the business day, for either PBSC or marrow...over time with products stored at 20°C whereas no notable change was observed with products stored at 4’C (p ɘ.0003). However for BM, platelet

  3. Total body irradiation in bone marrow transplantation: the influence of fractionation and delay of marrow infusion

    SciTech Connect

    Lichter, A.S.; Tracy, D.; Lam, W.C.; Order, S.E.

    1980-03-01

    Bone marrow transplantation (BMT) after total body irradiation (TBI) and cyclophosphamide is being employed increasingly in the therapy of end stage leukemia. Interstitial pneumonitis (IP) represents a major acute toxicity after allogeneic transplantation. A more rapid reconstitution of lymphoid organs and bone marrow post transplant may result in increased immune competence and hence fewer opportunistic pulmonary infections and IP. By delaying the infusion of marrow to 72 hr after TBI (1250 rad at 7.5 rad/min) instead of the customary 24 hr, we can demonstrate an increase in initial repopulation of thymus, spleen and bone marrow, with syngeneic transplants in Lewis rats. Interstitial pneumonitis may also be caused, in part, by the pulmonary toxicity of large single exposures of TBI. Clinical and laboratory data suggest that fractionated TBI may be less toxic to the lung. When fractionated TBI (625 rad x 2, 7.5 rad/min) is compared to single dose TBI (1250 rad, 7.5 rad/min), and increased initial repopulation of lymphoid organs is observed when fractionated therapy is employed. Delay in marrow infusion and fractionation of TBI exposure may have clinical advantages in patients who receive BMT.

  4. In vitro radiation studies on Ewing's sarcoma cell lines and human bone marrow: application to the clinical use of total body irradiation (TBI)

    SciTech Connect

    Kinsella, T.J.; Mitchell, J.B.; McPherson, S.; Miser, J.; Triche, T.; Glatstein, E.

    1984-07-01

    Patients with Ewing's sarcoma who present with a central axis or proximal extremity primary and/or with metastatic disease have a poor prognosis despite aggressive combination chemotherapy and local irradiation. In this high risk group of patients, total body irradiation (TBI) has been proposed as a systemic adjuvant. To aid in the design of a clinical TBI protocol, the authors have studied in the in vitro radiation response of two established cell lines of Ewing's sarcoma and human bone marrow CFUc. The Ewing's lines showed a larger D/sub 0/ and anti-n compared to the bone marrow CFU. No repair of potentially lethal radiation damage (PLDR) was found after 4.5 Gy in plateau phase Ewing's sarcoma cells. A theoretical split dose survival curve for both the Ewing's sarcoma lines and human bone marrow CFUc using this TBI schedule shows a significantly lower surviving fraction (10/sup -4/-10/sup -5/) for the bone marrow CFUc. Based on these in vitro results, two 4.0 Gy fractions separated by 24 hours is proposed as the TBI regimen. Because of the potentially irreversible damage to bone marrow, autologous bone marrow transplantation following the TBI is felt to be necessary. The details of this clinical protocol in high risk Ewing's sarcoma patients are outlined.

  5. Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major problem in patients with multiple myeloma is chemotherapy resistance, which develops in myeloma cells upon interaction with bone marrow stromal cells. However, few studies have determined the role of bone marrow adipocytes, a major component of stromal cells in the bone marrow, in myeloma ch...

  6. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 33 2012-07-01 2012-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a) Purpose. The in vivo bone marrow cytogenetic test is a mutagenicity test for the detection of...

  7. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 32 2014-07-01 2014-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a) Purpose. The in vivo bone marrow cytogenetic test is a mutagenicity test for the detection of...

  8. Identification of Bone Marrow-Derived Soluble Factors Regulating Human Mesenchymal Stem Cells for Bone Regeneration.

    PubMed

    Tsai, Tsung-Lin; Li, Wan-Ju

    2017-02-14

    Maintaining properties of human bone marrow-derived mesenchymal stem cells (BMSCs) in culture for regenerative applications remains a great challenge. An emerging approach of constructing a culture environment mimicking the bone marrow niche to regulate BMSC activities has been developed. In this study, we have demonstrated a systematic approach to identify soluble factors of interest extracted from human bone marrow and used them in BMSC culture for tissue regeneration. We have found that lipocalin-2 and prolactin are key factors in bone marrow, involved in regulating BMSC activities. Treating the cell with lipocalin-2 and prolactin delays cellular senescence of BMSCs and primes the cell for osteogenesis and chondrogenesis. We have also demonstrated that BMSCs pretreated with lipocalin-2 and prolactin can enhance the repair of calvarial defects in mice. Together, our study provides research evidence of using a viable approach to prime BMSC properties in vitro for improving cell-based tissue regeneration in vivo.

  9. Histochemistry of blood and bone marrow cells in pangolins.

    PubMed

    Caxton-Martins, A E

    1977-04-01

    Blood and bone marrow cells of pangolins have been examined histochemically. Sudanophilia, PAS positivity and acid phosphatase and alkaline phosphatase reactivity were confined to cells of the granulocytic and monocytic series, while peroxidase reactivity was confined to cells of the erythroid series. In this latter respect the pangolin is unique among mammals so far studied.

  10. Agent-Based Deterministic Modeling of the Bone Marrow Homeostasis.

    PubMed

    Kurhekar, Manish; Deshpande, Umesh

    2016-01-01

    Modeling of stem cells not only describes but also predicts how a stem cell's environment can control its fate. The first stem cell populations discovered were hematopoietic stem cells (HSCs). In this paper, we present a deterministic model of bone marrow (that hosts HSCs) that is consistent with several of the qualitative biological observations. This model incorporates stem cell death (apoptosis) after a certain number of cell divisions and also demonstrates that a single HSC can potentially populate the entire bone marrow. It also demonstrates that there is a production of sufficient number of differentiated cells (RBCs, WBCs, etc.). We prove that our model of bone marrow is biologically consistent and it overcomes the biological feasibility limitations of previously reported models. The major contribution of our model is the flexibility it allows in choosing model parameters which permits several different simulations to be carried out in silico without affecting the homeostatic properties of the model. We have also performed agent-based simulation of the model of bone marrow system proposed in this paper. We have also included parameter details and the results obtained from the simulation. The program of the agent-based simulation of the proposed model is made available on a publicly accessible website.

  11. Body/bone-marrow differential-temperature sensor

    NASA Technical Reports Server (NTRS)

    Anselmo, V. J.; Berdahl, C. M.

    1978-01-01

    Differential-temperature sensor developed to compare bone-marrow and body temperature in leukemia patients uses single stable amplifier to monitor temperature difference recorded by thermocouples. Errors are reduced by referencing temperatures to each other, not to separate calibration points.

  12. Agent-Based Deterministic Modeling of the Bone Marrow Homeostasis

    PubMed Central

    2016-01-01

    Modeling of stem cells not only describes but also predicts how a stem cell's environment can control its fate. The first stem cell populations discovered were hematopoietic stem cells (HSCs). In this paper, we present a deterministic model of bone marrow (that hosts HSCs) that is consistent with several of the qualitative biological observations. This model incorporates stem cell death (apoptosis) after a certain number of cell divisions and also demonstrates that a single HSC can potentially populate the entire bone marrow. It also demonstrates that there is a production of sufficient number of differentiated cells (RBCs, WBCs, etc.). We prove that our model of bone marrow is biologically consistent and it overcomes the biological feasibility limitations of previously reported models. The major contribution of our model is the flexibility it allows in choosing model parameters which permits several different simulations to be carried out in silico without affecting the homeostatic properties of the model. We have also performed agent-based simulation of the model of bone marrow system proposed in this paper. We have also included parameter details and the results obtained from the simulation. The program of the agent-based simulation of the proposed model is made available on a publicly accessible website. PMID:27340402

  13. Usefulness of bone marrow transplantation in the Hurler syndrome.

    PubMed

    Braunlin, Elizabeth A; Stauffer, Nanci R; Peters, Charles H; Bass, John L; Berry, James M; Hopwood, John J; Krivit, William

    2003-10-01

    The Hurler syndrome, an autosomal recessive storage disease of childhood, leads to death within the first decade of life from progressive deposition of glycosaminoglycans within the myointima of the coronary arteries and airways. Cardiac ultrasound findings of patients with this syndrome >10 years after successful bone marrow transplantation are described.

  14. Activation of Myeloid-Derived Suppressor Cells in Bone Marrow

    DTIC Science & Technology

    2013-12-01

    antigen in situ and in vitro. Atherosclerosis 135(1): 19–27. 21. Chow A, et al. (2011) Bone marrow CD169+ macrophages promote the retention of hematopoietic...renal injury-acceleration of atherosclerosis . Arterioscler Thromb Vasc Biol 31(12):2856–2864. 30. Lin SL, et al. (2010) Macrophage Wnt7b is critical for

  15. Treating Families of Bone Marrow Recipients and Donors

    ERIC Educational Resources Information Center

    Cohen, Marie; And Others

    1977-01-01

    Luekemia and aplastic anemia are beginning to be treated by bone marrow transplants, involving donors and recipients from the same family. Such intimate involvement in the patient's life and death struggles typically produces a family crisis and frequent maladaptive responses by various family members. (Author)

  16. Oestrogen-induced bone marrow aplasia in a dog.

    PubMed

    Bland-van den Berg, P; Bomzon, L; Lurie, A

    1978-12-01

    A case of oestrogen toxicity in the dog is described. The bone marrow was primarily affected with resultant non-regenerative anaemia, leukocytosis followed by leukopaenia, and thrombocytopaenia. Endometritis, toxaemia and disseminate intravascular coagulation were complicating factors. The case terminated fatally intensive therapy.

  17. Anaplasma platys in Bone Marrow Megakaryocytes of Young Dogs

    PubMed Central

    De Tommasi, A. Sara; Baneth, Gad; Breitschwerdt, Edward B.; Stanneck, Dorothee; Dantas-Torres, Filipe; Otranto, Domenico

    2014-01-01

    Anaplasma platys is an obligate intracellular rickettsial pathogen that infects platelets of dogs, forming basophilic intracellular morulae. In the present report, cellular inclusions were documented in bone marrow thrombocyte precursors of two young naturally infected dogs, indicating that A. platys can infect megakaryocytes and promegakaryocytes. PMID:24622106

  18. Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

    NASA Astrophysics Data System (ADS)

    Benkő, Klára; Pintye, Éva; Szabó, Boglárka; Géresi, Krisztina; Megyeri, Attila; Benkő, Ilona

    2008-12-01

    To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ—irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

  19. Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

    SciTech Connect

    Benko', Klara; Pintye, Eva; Szabo, Boglarka; Geresi, Krisztina; Megyeri, Attila; Benko, Ilona

    2008-12-08

    To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of {gamma}--irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD{sub 50} values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

  20. Biochemical and biophysical analyses of tissue-engineered bone obtained from three-dimensional culture of a subset of bone marrow mesenchymal stem cells.

    PubMed

    Ferro, Federico; Falini, Giuseppe; Spelat, Renza; D'Aurizio, Federica; Puppato, Elisa; Pandolfi, Maura; Beltrami, Antonio Paolo; Cesselli, Daniela; Beltrami, Carlo Alberto; Impiombato, Francesco Saverio Ambesi; Curcio, Francesco

    2010-12-01

    Grafts of tissue-engineered bone represent a promising alternative in the treatment of large and small bone defects. Current approaches are often badly tolerated by patients because of invasiveness, ethical problems, culture, and possibility of infection. Autologous grafts have been indicated as a solution to such problems. Because of tissue availability, many have proposed the use of cultured cells derived from bone marrow expanded in culture and induced to differentiate in bone tissue. Data reported in the literature show that it is possible to produce tissue substitutes in vitro indeed, but results are not always concordant regarding the in vitro produced bone quality. In the present work, we investigated bone formation in aggregates of human bone marrow-derived mesenchymal stem cells induced to differentiate in bone. After osteoinduction we characterized the mineral matrix produced using Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and X-ray powder diffraction. Cells were obtained from bone marrow, subjected to immunodepletion for CD3, CD11b, CD14, CD16, CD19, CD56, CD66b, and glycophorin A using RosetteSep and cultured in a new formulation of medium for four passages and then were allowed to form spontaneous aggregates. At the end of proliferation before aggregation, cells were analyzed by fluorescent activated cell sorting (FACS) for markers routinely used to characterize expanded mesenchymal stem cells and were found to be remarkably homogeneous for CD29 (99% ± 1%), CD73 (99% ± 1%), CD90 (95% ± 4%), CD105 (96% ± 4%), and CD133 (0% ± 1%) expression. Our results show that not only aggregated cells express the major markers of osteogenic differentiation, such as osteocalcin, osteonectin, osteopontin, and bone sialoprotein, but also the inorganic matrix is made of an apatite structurally and morphologically similar to native bone even without a scaffold.

  1. Bone marrow derived stem cell therapy for type 2 diabetes mellitus

    PubMed Central

    Chahine, Nassim Abi; Sissi, Salam; Abou-Joaude, Isabelle; Chalhoub, Louis

    2016-01-01

    In this study, 6 patients with type 2 diabetes (T2D) underwent autologous bone marrow mononuclear stem cell (BM-MNSC) infusion into the celiac and superior mesenteric arteries without pretreatment with any myeloablative or immune-suppressive therapy. Five of 6 (83%) showed normalization of their fasting glucose and the glycosylated hemoglobin (HbA1C) with significant reduction of their medication requirements. The HbA1C dropped on average 2.2 points. The three patients with diabetic complications showed improvement or stabilization and most patients reported improved energy and stamina. The durations of response varied between 6 months and 2 years. No patients had any significant adverse effects. PMID:28066789

  2. Estradiol synthesis and release in cultured female rat bone marrow stem cells.

    PubMed

    Zhang, Dalei; Yang, Bei; Zou, Weiying; Lu, Xiaying; Xiong, Mingdi; Wu, Lei; Wang, Jinglei; Gao, Junhong; Xu, Sifan; Zou, Ting

    2013-01-01

    Bone marrow stem cells (BMSCs) have the capacity to differentiate into mature cell types of multiple tissues. Thus, they represent an alternative source for organ-specific cell replacement therapy in degenerative diseases. In this study, we demonstrated that female rat BMSCs could differentiate into steroidogenic cells with the capacity for de novo synthesis of Estradiol-17 β (E2) under high glucose culture conditions with or without retinoic acid (RA). The cultured BMSCs could express the mRNA and protein for P450arom, the enzyme responsible for estrogen biosynthesis. Moreover, radioimmunoassay revealed that BMSCs cultured in the present culture system produced and secreted significant amounts of testosterone, androstenedione, and E2. In addition, RA promoted E2 secretion but did not affect the levels of androgen. These results indicate that BMSCs can synthesize and release E2 and may contribute to autologous transplantation therapy for estrogen deficiency.

  3. A Dosimetric Study of Radionuclide Therapy for Bone Marrow Ablation.

    NASA Astrophysics Data System (ADS)

    Bayouth, John Ellis

    In a phase I clinical trial, six multiple myeloma patients, who were non-responsive to conventional therapy and were scheduled for bone marrow transplantation, received Holmium-166 (166Ho) labeled to a bone seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane -1,4,7,10-tetramethylene-phosphonic acid), for the purpose of bone marrow ablation. The specific aims of my research within this protocol were to evaluate the toxicity and efficacy of 166Ho DOTMP by quantifying the in vivo pharmacokinetics and radiation dosimetry, and by correlating these results to the biologic response observed. The reproducibility of pharmacokinetics from multiple injections of 166 Ho DOTMP administered to these myeloma patients was demonstrated from both blood and whole body retention. The skeletal concentration of 166 Ho DOTMP was heterogenous in all six patients: high in the ribs, pelvis, and lumbar vertebrae regions, and relatively low in the femurs, arms, and head. A novel technique was developed to calculate the radiation dose to the bone marrow in each skeletal ROI, and was applied to all six 166 Ho DOTMP patients. Radiation dose estimates for the bone marrow calculated using the standard MIRD "S" factors were compared with the average values derived from the heterogenous distribution of activity in the skeleton (i.e., the regional technique). The results from the two techniques were significantly different; the average of the dose estimates from the regional technique were typically 30% greater. Furthermore, the regional technique provided a range of radiation doses for the entire marrow volume, while the MIRD "S" factors only provided a single value. Dose volume histogram analysis of data from the regional technique indicated a range of dose estimates that varied by a factor of 10 between the high dose and low dose regions. Finally, the observed clinical response of cells and abnormal proteins measured in bone marrow aspirates and peripheral blood samples were compared with

  4. Femoral fracture after harvesting of autologous bone graft using a reamer/irrigator/aspirator.

    PubMed

    Giori, Nicholas J; Beaupre, Gary S

    2011-02-01

    A case of postoperative fracture in the donor femur after obtaining autologous bone graft with a reamer/irrigator/aspirator is presented. This procedure was successful in healing a difficult femoral nonunion, but the patient sustained a fracture of the contralateral (bone graft donor) femur 20 days after surgery. A mechanical analysis is conducted of this case and recommendations are made. Unrestricted weightbearing on a limb that has undergone reamer/irrigator/aspirator bone graft harvesting, particularly in a noncompliant patient, is probably inadvisable. If possible, one should obtain bone graft from the same limb as the fracture being treated because this will leave the patient with one unaltered limb for mobilization.

  5. Transplantation of umbilical cord and bone marrow-derived mesenchymal stem cells in a patient with relapsing-remitting multiple sclerosis

    PubMed Central

    Hou, Zong-liu; Liu, Ying; Mao, Xi-Hong; Wei, Chuan-yu; Meng, Ming-yao; Liu, Yun-hong; Zhuyun Yang, Zara; Zhu, Hongmei; Short, Martin; Bernard, Claude; Xiao, Zhi-cheng

    2013-01-01

    There is currently great interest in the use of mesenchymal stem cells as a therapy for multiple sclerosis with potential to both ameliorate inflammatory processes as well as improve regeneration and repair. Although most clinical studies have used autologous bone marrow-derived mesenchymal stem cells, other sources such as allogeneic umbilical cord-derived cells may provide a more accessible and practical supply of cells for transplantation. In this case report we present the treatment of aggressive multiple sclerosis with multiple allogenic human umbilical cord-derived mesenchymal stem cell and autologous bone marrow-derived mesenchymal stem cells over a 4 y period. The treatments were tolerated well with no significant adverse events. Clinical and radiological disease appeared to be suppressed following the treatments and support the expansion of mesenchymal stem cell transplantation into clinical trials as a potential novel therapy for patients with aggressive multiple sclerosis. PMID:24192520

  6. Low-frequency vibration treatment of bone marrow stromal cells induces bone repair in vivo

    PubMed Central

    He, Shengwei; Zhao, Wenzhi; Zhang, Lu; Mi, Lidong; Du, Guangyu; Sun, Chuanxiu; Sun, Xuegang

    2017-01-01

    Objective(s): To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo. Materials and Methods: Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To test differentiation, bones were isolated and demineralized, supplemented with bone marrow stromal cells, and implanted into humerus bone defects. Varying frequencies of vibration (0, 12.5, 25, 50, and 100 Hz) were applied to each group for 30 min each day for four weeks. When the bone defects integrated, they were then removed for histological examination. mRNA transcript levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligan, and pre-collagen type 1 α were measured. Results: Humeri implanted with bone marrow stromal cells displayed elevated callus levels and wider, more prevalent, and denser trabeculae following treatment at 25 and 50 Hz. The mRNA levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligand, and pre-collagen type 1 α were also markedly higher following 25 and 50 Hz treatment. Conclusion: Low frequency (25–50 Hz) vibration in vivo can promote bone marrow stromal cell differentiation and repair bone injury. PMID:28133520

  7. Autologous bone grafting on steroids: preliminary clinical results. A novel treatment for nonunions and segmental bone defects.

    PubMed

    Miller, Micah A; Ivkovic, Alan; Porter, Ryan; Harris, Mitchel B; Estok, Daniel M; Smith, R Malcolm; Evans, Christopher H; Vrahas, Mark S

    2011-04-01

    Clinical management of delayed healing or nonunion of long bone fractures and segmental bone defects poses a substantial orthopaedic challenge. Surgical advances and bone tissue engineering are providing new avenues to stimulate bone growth in cases of bone loss and nonunion. The reamer-irrigator-aspirator (RIA) device allows surgeons to aspirate the medullary contents of long bones and use the progenitor-rich "flow-through" fraction in autologous bone grafting. Dexamethasone (DEX) is a synthetic steroid that has been shown to induce osteoblastic differentiation. A series of 13 patients treated with RIA bone grafting enhanced with DEX for nonunion or segmental defect was examined retrospectively to assess the quality of bony union and clinical outcomes. Despite the initial poor prognoses, promising results were achieved using this technique; and given the complexity of these cases the observed success is of great value and warrants controlled study into both standardisation of the procedure and concentration of the grafting material.

  8. Combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil causes trabecular bone loss, bone marrow cell depletion and marrow adiposity in female rats.

    PubMed

    Fan, Chiaming; Georgiou, Kristen R; McKinnon, Ross A; Keefe, Dorothy M K; Howe, Peter R C; Xian, Cory J

    2016-05-01

    The introduction of anthracyclines to adjuvant chemotherapy has increased survival rates among breast cancer patients. Cyclophosphamide, epirubicin and 5-fluorouracil (CEF) combination therapy is now one of the preferred regimens for treating node-positive breast cancer due to better survival with less toxicity involved. Despite the increasing use of CEF, its potential in causing adverse skeletal effects remains unclear. Using a mature female rat model mimicking the clinical setting, this study examined the effects of CEF treatment on bone and bone marrow in long bones. Following six cycles of CEF treatment (weekly intravenous injections of cyclophosphamide at 10 mg/kg, epirubicin at 2.5 mg/kg and 5-flurouracil at 10 mg/kg), a significant reduction in trabecular bone volume was observed at the metaphysis, which was associated with a reduced serum level of bone formation marker alkaline phosphatase (ALP), increased trends of osteoclast density and osteoclast area at the metaphysis, as well as an increased size of osteoclasts being formed from the bone marrow cells ex vivo. Moreover, a severe reduction of bone marrow cellularity was observed following CEF treatment, which was accompanied by an increase in marrow adipose tissue volume. This increase in marrow adiposity was associated with an expansion in adipocyte size but not in marrow adipocyte density. Overall, this study indicates that six cycles of CEF chemotherapy may induce some bone loss and severe bone marrow damage. Mechanisms for CEF-induced bone/bone marrow pathologies and potential preventive strategies warrant further investigation.

  9. High-dose melphalan and total body irradiation with bone marrow transplantation for refractory malignancies.

    PubMed

    Spitzer, G; Jagannath, S; Dicke, K A; Armitage, J; Zander, A R; Vellekoop, L; Horwitz, L; Cabanillas, F; Zagars, G K; Velasquez, W S

    1986-06-01

    We investigated if high dose melphalan and total body irradiation could be administered to adult patients with acceptable toxicity. Nineteen adult patients with relapsed disease, 15 of them having hematologic malignancies, were treated with high-dose melphalan (100 mg/m2-140 mg/m2) divided over 2 consecutive days followed by a rest period of 4 days before receiving total body irradiation, 850 rad administered in five fractionated doses over 3 days. Subsequently 11 patients received autologous, seven allogeneic and one syngeneic, bone marrow transplantation. All patients had severe myelosuppression and the major extramedullary toxicity was mucositis. There were three early deaths, two related to septicemia and one to graft-versus-host disease with associated cytomegalovirus pneumonitis. All patients were heavily pretreated, and 16 were demonstrating progressive disease on alternative salvage therapies at the time of bone marrow transplantation. Two of the 16 evaluable patients (12.5%) achieved complete remissions, and 10 (63%) achieved partial remissions for a total response rate of 75%. One patient is a long-term disease-free survivor (over 1 yr). An occasional patient may be cured by this approach. The combination of melphalan, an alternative alkylating agent to cyclophosphamide and total body irradiation are associated with moderate gastrointestinal toxicity in heavily pretreated adult patients. The combination warrants further investigation in a less heavily pretreated population to determine more accurately the complete response rate.

  10. Adipose Stem Cells as Alternatives for Bone Marrow Mesenchymal Stem Cells in Oral Ulcer Healing

    PubMed Central

    Aziz Aly, Lobna Abdel; Menoufy, Hala El-; Ragae, Alyaa; Rashed, Laila Ahmed; Sabry, Dina

    2012-01-01

    Background and Objectives Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. Methods and Results Oral ulcers were induced by topical application of formocresol in the oral cavity of dogs. Transplantation of undifferentiated GFP-labeled Autologous Bone Marrow Stem Cell (BMSCs), Adipose Derived Stem Cell (ADSCs) or vehicle (saline) was injected around the ulcer in each group. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) was detected in MSCs by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Expression of VEGF and collagen genes was detected in biopsies from all ulcers. Results: MSCs expressed mRNA for VEGF MSCs transplantation significantly accelerated oral ulcer healing compared with controls. There was increased expression of both collagen and VEGF genes in MSCs-treated ulcers compared to controls. Conclusions MSCs transplantation may help to accelerate oral ulcer healing, possibly through the induction of angiogenesis by VEGF together with increased intracellular matrix formation as detected by increased collagen gene expression. This body of work has provided evidence supporting clinical applications of adipose-derived cells in safety and efficacy trials as an alternative for bone marrow mesenchymal stem cells in oral ulcer healing. PMID:24298363

  11. Differentiation of lymphatic endothelial cells from bone marrow mesenchymal stem cells with VEGFs.

    PubMed

    Wei, Luwan; Liu, Yanli; Chen, Guoling; Fang, Yunhai; Song, Xianrang; Dong, Ping; Gao, Jie; Liu, Rong; Ding, Zhaoxi; Bi, Yushun; Liu, Zhiyu

    2012-12-01

    Although there have been many experimental studies demonstrating that bone marrow-derived mesenchymal stem cells (MSCs) have the potential to differentiate into mesenchymal tissues such as osteocytes, chondrocytes, and adipocytes in vivo and in vitro, little information is available regarding their potential to differentiate into lymphatic endothelial cells. Therefore, we chose to investigate differentiation of MSCs into lymphatic endothelial cells using stimulation with members of the vascular endothelial growth factor (VEGFs) family. Rat MSCs were isolated from bone marrow aspirate of Sprague-Dawley rats as previously described and characterized with flow cytometry for surface markers CD14, CD34, CD29, and CD90. Purified MSCs were plated and cultured in the presence of VEGF-A, VEGF-C, or the combination of both for 10 days. We examined the cells for Prox-1 and LYVE-1 by immunocytochemistry, RT-PCR, and Western blot analysis. Results demonstrated that compared to controls, cell differentiated with VEGF-A, VEGF-C and VEGF-A+VEGF-C expressed Prox-1 and LYVE-1. Our results indicate that MSCs induced by VEGFs are capable of differentiating into lymphatic endothelial-like cells in vitro, and this response has the potential to make them attractive candidates for the development of autologous tissue grafts for future therapy.

  12. Bone marrow necrosis in a cat infected with feline leukemia virus.

    PubMed

    Shimoda, T; Shiranaga, N; Mashita, T; Hasegawa, A

    2000-01-01

    A one-year old castrated male cat was admitted to the hospital with vomiting and diarrhea. Laboratory examination revealed pancytopenia and positive for FeLV antigen. A bone marrow examination indicated necrosis of the nucleated cells. Based on these findings, the cat was diagnosed as bone marrow necrosis. Pancytopenia was effectively treated with corticosteroids. Re-examination of the bone marrow confirmed a recovery of normal hematopoietic cells with a infiltration of many macrophages. It is strongly suspected that the bone marrow necrosis in this case could be associated with a bone marrow suppression due to FeLV infection.

  13. Stem cell niche failure concerns bone marrow failure--a diagnostic and therapeutic consideration.

    PubMed

    Law, Sujata; Chaudhuri, Samaresh

    2011-01-01

    Diseases of the bone marrow often referred to as "Bone marrow failure" have complicated pathophysiological picture with respect to hematopoietic systemic function. The reason for such bone marrow disorder is not well understood till date, although some sporadic etiological sources have been described earlier. With the advent of current investigations, hematopoietic stem cell involvement together with the failure of signaling interaction within the bone marrow niche has been found to reveal interesting correlations with the disease onset. The present review furnishes justification for bone marrow failure as a concern of stem cell niche failure and hints at providing important clues for disease diagnosis and therapeutic maneuver.

  14. Demineralized Bone Matrix (DBM) as a Bone Void Filler in Lumbar Interbody Fusion: A Prospective Pilot Study of Simultaneous DBM and Autologous Bone Grafts

    PubMed Central

    Kim, Bum-Joon; Kim, Se-Hoon; Lee, Haebin; Lee, Seung-Hwan; Kim, Won-Hyung; Jin, Sung-Won

    2017-01-01

    Objective Solid bone fusion is an essential process in spinal stabilization surgery. Recently, as several minimally invasive spinal surgeries have developed, a need of artificial bone substitutes such as demineralized bone matrix (DBM), has arisen. We investigated the in vivo bone growth rate of DBM as a bone void filler compared to a local autologous bone grafts. Methods From April 2014 to August 2015, 20 patients with a one or two-level spinal stenosis were included. A posterior lumbar interbody fusion using two cages and pedicle screw fixation was performed for every patient, and each cage was packed with autologous local bone and DBM. Clinical outcomes were assessed using the Numeric Rating Scale (NRS) of leg pain and back pain and the Korean Oswestry Disability Index (K-ODI). Clinical outcome parameters and range of motion (ROM) of the operated level were collected preoperatively and at 3 months, 6 months, and 1 year postoperatively. Computed tomography was performed 1 year after fusion surgery and bone growth of the autologous bone grafts and DBM were analyzed by ImageJ software. Results Eighteen patients completed 1 year of follow-up, including 10 men and 8 women, and the mean age was 56.4 (32–71). The operated level ranged from L3/4 to L5/S1. Eleven patients had single level and 7 patients had two-level repairs. The mean back pain NRS improved from 4.61 to 2.78 (p=0.003) and the leg pain NRS improved from 6.89 to 2.39 (p<0.001). The mean K-ODI score also improved from 27.33 to 13.83 (p<0.001). The ROM decreased below 2.0 degrees at the 3-month assessment, and remained less than 2 degrees through the 1 year postoperative assessment. Every local autologous bone graft and DBM packed cage showed bone bridge formation. On the quantitative analysis of bone growth, the autologous bone grafts showed significantly higher bone growth compared to DBM on both coronal and sagittal images (p<0.001 and p=0.028, respectively). Osteoporotic patients showed less bone

  15. Bone marrow-derived cells homing for self-repair of periodontal tissues: a histological characterization and expression analysis.

    PubMed

    Wang, Yan; Zhou, Lili; Li, Chen; Xie, Han; Lu, Yuwang; Wu, Ying; Liu, Hongwei

    2015-01-01

    Periodontitis, a disease leads to the formation of periodontal defect, can result in tooth loss if left untreated. The therapies to repair/regenerate periodontal tissues have attracted lots of attention these years. Bone marrow-derived cells (BMDCs), a group of cells containing heterogeneous stem/progenitor cells, are capable of homing to injured tissues and participating in tissue repair/regeneration. The amplification of autologous BMDCs' potential in homing for self-repair/regeneration, therefore, might be considered as an alternative therapy except for traditional cell transplantation. However, the knowledge of the BMDCs' homing and participation in periodontal repair/regeneration is still known little. For the purpose of directly observing BMDCs' involvement in periodontal repair, chimeric mouse models were established to make their bone marrow cells reconstituted with cells expressing green enhanced fluorescence protein (EGFP) in this study. One month after bone marrow transplantation, periodontal defects were made on the mesial side of bilateral maxillary first molars in chimeric mice. The green fluorescence protein-positive (GFP+) BMDCS in periodontal defect regions were examined by bioluminescent imaging and immunofluorescence staining. GFP+ BMDCs were found to aggregate in the periodontal defect regions and emerge in newly-formed bones or fibers. Some of them also co-expressed markers of fibroblasts, osteoblasts or vascular endothelial cells. These results indicated that BMDCs might contribute to the formation of new fibers, bones and blood vessels during periodontal repair. In conclusion, we speculated that autologous BMDCs were capable of negotiating into the surgical sites created by periodontal operation and participating in tissue repair.

  16. Bone marrow-derived cells homing for self-repair of periodontal tissues: a histological characterization and expression analysis

    PubMed Central

    Wang, Yan; Zhou, Lili; Li, Chen; Xie, Han; Lu, Yuwang; Wu, Ying; Liu, Hongwei

    2015-01-01

    Periodontitis, a disease leads to the formation of periodontal defect, can result in tooth loss if left untreated. The therapies to repair/regenerate periodontal tissues have attracted lots of attention these years. Bone marrow-derived cells (BMDCs), a group of cells containing heterogeneous stem/progenitor cells, are capable of homing to injured tissues and participating in tissue repair/regeneration. The amplification of autologous BMDCs’ potential in homing for self-repair/regeneration, therefore, might be considered as an alternative therapy except for traditional cell transplantation. However, the knowledge of the BMDCs’ homing and participation in periodontal repair/regeneration is still known little. For the purpose of directly observing BMDCs’ involvement in periodontal repair, chimeric mouse models were established to make their bone marrow cells reconstituted with cells expressing green enhanced fluorescence protein (EGFP) in this study. One month after bone marrow transplantation, periodontal defects were made on the mesial side of bilateral maxillary first molars in chimeric mice. The green fluorescence protein-positive (GFP+) BMDCS in periodontal defect regions were examined by bioluminescent imaging and immunofluorescence staining. GFP+ BMDCs were found to aggregate in the periodontal defect regions and emerge in newly-formed bones or fibers. Some of them also co-expressed markers of fibroblasts, osteoblasts or vascular endothelial cells. These results indicated that BMDCs might contribute to the formation of new fibers, bones and blood vessels during periodontal repair. In conclusion, we speculated that autologous BMDCs were capable of negotiating into the surgical sites created by periodontal operation and participating in tissue repair. PMID:26722424

  17. Bone marrow to liver: the blood of Prometheus.

    PubMed

    Theise, Neil D; Krause, Diane S

    2002-12-01

    The existence of hepatic stem or progenitor cells has been controversial for decades, though it was presumed that if such cells existed, they would lie within the liver. There is now consensus, however, that not only do facultative hepatic stem cells exist within the liver, but also that cells from extra-hepatic sites, in particular the bone marrow, can contribute to hepatocyte and cholangiocyte regeneration. Despite confidence that engraftment of marrow cells in the liver occurs, the mechanistic details of this process remain poorly understood. Moreover, the physiological importance and therapeutic utility of this phenomenon remains controversial.

  18. Pressure and shear stress in trabecular bone marrow during whole bone loading.

    PubMed

    Metzger, Thomas A; Schwaner, Stephen A; LaNeve, Anthony J; Kreipke, Tyler C; Niebur, Glen L

    2015-09-18

    Skeletal adaptation to mechanical loading is controlled by mechanobiological signaling. Osteocytes are highly responsive to applied strains, and are the key mechanosensory cells in bone. However, many cells residing in the marrow also respond to mechanical cues such as hydrostatic pressure and shear stress, and hence could play a role in skeletal adaptation. Trabecular bone encapsulates marrow, forming a poroelastic solid. According to the mechanical theory, deformation of the pores induces motion in the fluid-like marrow, resulting in pressure and velocity gradients. The latter results in shear stress acting between the components of the marrow. To characterize the mechanical environment of trabecular bone marrow in situ, pore pressure within the trabecular compartment of whole porcine femurs was measured with miniature pressure transducers during stress-relaxation and cyclic loading. Pressure gradients ranging from 0.013 to 0.46 kPa/mm were measured during loading. This range was consistent with calculated pressure gradients from continuum scale poroelastic models with the same permeability. Micro-scale computational fluid dynamics models created from computed tomography images were used to calculate the micromechanical stress in the marrow using the measured pressure differentials as boundary conditions. The volume averaged shear stress in the marrow ranged from 1.67 to 24.55 Pa during cyclic loading, which exceeds the mechanostimulatory threshold for mesenchymal lineage cells. Thus, the loading of bone through activities of daily living may be an essential component of bone marrow health and mechanobiology. Additional studies of cell-level interactions during loading in healthy and disease conditions will provide further incite into marrow mechanobiology.

  19. Bone marrow regeneration following fractionated radiation therapy. [/sup 60/Co or HMV linear accelerator

    SciTech Connect

    Hill, D.R.; Benak, S.B.; Phillips, T.L.; Price, D.C.

    1980-09-01

    Eight patients were studied with /sup 99m/Tc-S colloid bone marrow scans prior to or at various intervals following megavoltage irradiation. None had marrow tumor involvement and none had chemotherapy during the study period. If reticuloendothelial marrow activity reflects hematopoietic activity, there appears to be maximal depression of marrow activity 6 months post irradiation. Total nodal irradiated patients regenerated marrow as well as local field patients despite the larger marrow volume irradiated.

  20. Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

    PubMed

    Prisby, Rhonda D

    2014-07-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p<0.05) in the old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p<0.05) 262%, 375% and 263%, respectively, in the old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in the old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in "microvascular dead space" in regard to loss of patency and vasomotor function as opposed to necrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the

  1. Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms

    PubMed Central

    Herroon, Mackenzie K.; Rajagurubandara, Erandi; Hardaway, Aimalie L.; Powell, Katelyn; Turchick, Audrey; Feldmann, Daniel; Podgorski, Izabela

    2013-01-01

    Incidence of skeletal metastases and death from prostate cancer greatly increases with age and obesity, conditions which increase marrow adiposity. Bone marrow adipocytes are metabolically active components of bone metastatic niche that modulate the function of neighboring cells; yet the mechanisms of their involvement in tumor behavior in bone have not been explored. In this study, using experimental models of intraosseous tumor growth and diet-induced obesity, we demonstrate the promoting effects of marrow fat on growth and progression of skeletal prostate tumors. We reveal that exposure to lipids supplied by marrow adipocytes induces expression of lipid chaperone FABP4, pro-inflammatory interleukin IL-1β, and oxidative stress protein HMOX-1 in metastatic tumor cells and stimulates their growth and invasiveness. We show that FABP4 is highly overexpressed in prostate skeletal tumors from obese mice and in bone metastasis samples from prostate cancer patients. In addition, we provide results suggestive of bi-directional interaction between FABP4 and PPARγ pathways that may be driving aggressive tumor cell behavior in bone. Together, our data provide evidence for functional relationship between bone marrow adiposity and metastatic prostate cancers and unravel the FABP4/IL-1β axis as a potential therapeutic target for this presently incurable disease. PMID:24240026

  2. [Bone and Stem Cells. Immune cell regulation by the bone marrow niche].

    PubMed

    Terashima, Asuka; Takayanagi, Hiroshi

    2014-04-01

    Adult hematopoietic stem cells (HSCs) are maintained in the bone marrow and give rise to all blood cell types. The maintenance and the differentiation of blood cells including immune cells are essential for host defense and oxygen delivery. HSCs are maintained in microenvironments called stem cell niches, which consists of various cell types in bone marrow. Recently, new visualization technologies and assay systems brought advances in studies on the stem cell niche. In addition, several reports demonstrated that osteoblasts and osteocytes regulate not only HSC homeostasis but also immune cell differentiation, suggesting a close relationship between bone cells and HSCs.

  3. Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow

    PubMed Central

    Yu, Vionnie W.C.; Saez, Borja; Cook, Colleen; Lotinun, Sutada; Pardo-Saganta, Ana; Wang, Ying-Hua; Lymperi, Stefania; Ferraro, Francesca; Raaijmakers, Marc H.G.P.; Wu, Joy Y.; Zhou, Lan; Rajagopal, Jayaraj; Kronenberg, Henry M.; Baron, Roland

    2015-01-01

    Production of the cells that ultimately populate the thymus to generate α/β T cells has been controversial, and their molecular drivers remain undefined. Here, we report that specific deletion of bone-producing osteocalcin (Ocn)-expressing cells in vivo markedly reduces T-competent progenitors and thymus-homing receptor expression among bone marrow hematopoietic cells. Decreased intrathymic T cell precursors and decreased generation of mature T cells occurred despite normal thymic function. The Notch ligand DLL4 is abundantly expressed on bone marrow Ocn+ cells, and selective depletion of DLL4 from these cells recapitulated the thymopoietic abnormality. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell–based adaptive immunity. PMID:25918341

  4. [Bone and Stem Cells. Bone marrow microenvironment niches for hematopoietic stem and progenitor cells].

    PubMed

    Nagasawa, Takashi

    2014-04-01

    In bone marrow, the special microenvironments known as niches control proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs) . However, the identity and functions of the niches has been a subject of longstanding debate. Although it has been reported previously that osteoblasts lining the bone surface act as HSC niches, their precise role in HSC maintenance remains unclear. On the other hand, the adipo-osteogenic progenitors with long processes, termed CXCL12-abundant reticular (CAR) cells, which preferentially express the chemokine CXCL12, stem cell factor (SCF) , leptin receptor and PDGF receptor-β were identified in the bone marrow. Recent studies revealed that endothelial cells of bone marrow vascular sinuses and CAR cells provided niches for HSCs. The identity and functions of various other candidate HSC niche cells, including nestin-expressing cells and Schwann cells would also be discussed in this review.

  5. Discoidin Receptor 2 Controls Bone Formation and Marrow Adipogenesis.

    PubMed

    Ge, Chunxi; Wang, Zhengyan; Zhao, Guisheng; Li, Binbin; Liao, Jinhui; Sun, Hanshi; Franceschi, Renny T

    2016-12-01

    Cell-extracellular matrix (ECM) interactions play major roles in controlling progenitor cell fate and differentiation. The receptor tyrosine kinase, discoidin domain receptor 2 (DDR2), is an important mediator of interactions between cells and fibrillar collagens. DDR2 signals through both ERK1/2 and p38 MAP kinase, which stimulate osteoblast differentiation and bone formation. Here we show that DDR2 is critical for skeletal development and differentiation of marrow progenitor cells to osteoblasts while suppressing marrow adipogenesis. Smallie mice (Ddr2(slie/slie) ), which contain a nonfunctional Ddr2 allele, have multiple skeletal defects. A progressive decrease in tibial trabecular bone volume/total volume (BV/TV) was observed when wild-type (WT), Ddr2(wt/slie) , and Ddr2(slie/slie) mice were compared. These changes were associated with reduced trabecular number (Tb.N) and trabecular thickness (Tb.Th) and increased trabecular spacing (Tb.Sp) in both males and females, but reduced cortical thickness only in Ddr2(slie/slie) females. Bone changes were attributed to decreased bone formation rather than increased osteoclast activity. Significantly, marrow fat and adipocyte-specific mRNA expression were significantly elevated in Ddr2(slie/slie) animals. Additional skeletal defects include widened calvarial sutures and reduced vertebral trabecular bone. To examine the role of DDR2 signaling in cell differentiation, bone marrow stromal cells (BMSCs) were grown under osteogenic and adipogenic conditions. Ddr2(slie/slie) cells exhibited defective osteoblast differentiation and accelerated adipogenesis. Changes in differentiation were related to activity of runt-related transcription factor 2 (RUNX2) and PPARγ, transcription factors that are both controlled by MAPK-dependent phosphorylation. Specifically, the defective osteoblast differentiation in calvarial cells from Ddr2(slie/slie) mice was associated with reduced ERK/MAP kinase and RUNX2-S319 phosphorylation and could

  6. A patient with familial bone marrow failure and an inversion of chromosome 8.

    PubMed

    Buchbinder, David Kyle; Zadeh, Touran; Nugent, Diane

    2011-12-01

    Familial bone marrow failure has been associated with a variety of chromosomal aberrations. Chromosome 8 abnormalities have been described in association with neoplastic and hematologic disorders; however, to our knowledge, inversion of the long arm of chromosome 8 has not been described in the context of familial bone marrow failure. We describe a 9-year-old female with familial bone marrow failure and an inversion of chromosome 8 [inv (8) (q22, q24.3)]. Given the importance of considering the genetic determinants of familial bone marrow failure, the potential role of chromosome 8 abnormalities in the development of marrow failure is discussed.

  7. Treatment of oroantral fistula with autologous bone graft and application of a non-reabsorbable membrane

    PubMed Central

    Scattarella, Adele; Ballini, Andrea; Grassi, Felice Roberto; Carbonara, Andrea; Ciccolella, Francesco; Dituri, Angela; Nardi, Gianna Maria; Cantore, Stefania; Pettini, Francesco

    2010-01-01

    Aim: The aim of the current report is to illustrate an alternative technique for the treatment of oroantral fistula (OAF), using an autologous bone graft integrated by xenologous particulate bone graft. Background: Acute and chronic oroantral communications (OAC, OAF) can occur as a result of inadequate treatment. In fact surgical procedures into the maxillary posterior area can lead to inadvertent communication with the maxillary sinus. Spontaneous healing can occur in defects smaller than 3 mm while larger communications should be treated without delay, in order to avoid sinusitis. The most used techniques for the treatment of OAF involve buccal flap, palatal rotation - advancement flap, Bichat fat pad. All these surgical procedures are connected with a significant risk of morbidity of the donor site, infections, avascular flap necrosis, impossibility to repeat the surgical technique after clinical failure, and patient discomfort. Case presentation: We report a 65-years-old female patient who came to our attention for the presence of an OAF and was treated using an autologous bone graft integrated by xenologous particulate bone graft. An expanded polytetrafluoroethylene titanium-reinforced membrane (Gore-Tex ®) was used in order to obtain an optimal reconstruction of soft tissues and to assure the preservation of the bone graft from epithelial connection. Conclusions: This surgical procedure showed a good stability of the bone grafts, with a complete resolution of the OAF, optimal management of complications, including patient discomfort, and good regeneration of soft tissues. Clinical significance: The principal advantage of the use of autologous bone graft with an expanded polytetrafluoroethylene titanium-reinforced membrane (Gore-Tex ®) to guide the bone regeneration is that it assures a predictable healing and allows a possible following implant-prosthetic rehabilitation. PMID:20714437

  8. Bone Marrow Blood Vessels: Normal and Neoplastic Niche

    PubMed Central

    Shahrabi, Saeid; Rezaeeyan, Hadi; Ahmadzadeh, Ahmad; Shahjahani, Mohammad; Saki, Najmaldin

    2016-01-01

    Blood vessels are among the most important factors in the transport of materials such as nutrients and oxygen. This study will review the role of blood vessels in normal bone marrow hematopoiesis as well as pathological conditions like leukemia and metastasis. Relevant literature was identified by a Pubmed search (1992-2016) of English-language papers using the terms bone marrow, leukemia, metastasis, and vessel. Given that blood vessels are conduits for the transfer of nutrients, they create a favorable situation for cancer cells and cause their growth and development. On the other hand, blood vessels protect leukemia cells against chemotherapy drugs. Finally, it may be concluded that the vessels are an important factor in the development of malignant diseases. PMID:27994770

  9. Total lymphatic irradiation and bone marrow in human heart transplantation

    SciTech Connect

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-08-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem.

  10. Juvenile xanthogranuloma with clonal proliferation in the bone marrow.

    PubMed

    Mały, Ewa; Przyborska, Marta; Rybczyńska, Aleksandra; Konatkowska, Benigna; Nowak, Jerzy; Januszkiewicz, Danuta

    2012-04-01

    The triple association between juvenile xanthogranuloma (JXG), juvenile myelomonocytic leukemia and neurofibromatosis was described in literature in about 20 cases. In this paper, the case of an 11-month-old infant boy with a disseminated JXG with unusual cytogenetic representation in the bone marrow was reported. Neurofibromatosis and juvenile myelomonocytic leukemia were excluded, just the same as other leukemias. Bone marrow and peripheral blood cytogenetic analysis revealed a karyotype with many rearrangements 46,XY,-6,der(12)t(6;12)(p21;p13),del(7)(p13p22),+9 once described in the literature as a B-acute lymphoblastic leukemia case. On the contrary, in our patient immunologic testing demonstrated a high activity of T lymphocytes, however, inflammation was excluded. To the best of our knowledge this is the first described case of systemic JXG with determined karyotype representing unusual chromosomal aberrations.

  11. Bone marrow-derived stem cells initiate pancreatic regeneration.

    PubMed

    Hess, David; Li, Li; Martin, Matthew; Sakano, Seiji; Hill, David; Strutt, Brenda; Thyssen, Sandra; Gray, Douglas A; Bhatia, Mickie

    2003-07-01

    We show that transplantation of adult bone marrow-derived cells expressing c-kit reduces hyperglycemia in mice with streptozotocin-induced pancreatic damage. Although quantitative analysis of the pancreas revealed a low frequency of donor insulin-positive cells, these cells were not present at the onset of blood glucose reduction. Instead, the majority of transplanted cells were localized to ductal and islet structures, and their presence was accompanied by a proliferation of recipient pancreatic cells that resulted in insulin production. The capacity of transplanted bone marrow-derived stem cells to initiate endogenous pancreatic tissue regeneration represents a previously unrecognized means by which these cells can contribute to the restoration of organ function.

  12. A stochastic model of radiation-induced bone marrow damage

    SciTech Connect

    Cotlet, G.; Blue, T.E.

    2000-03-01

    A stochastic model, based on consensus principles from radiation biology, is used to estimate bone-marrow stem cell pool survival (CFU-S and stroma cells) after irradiation. The dose response model consists of three coupled first order linear differential equations which quantitatively describe time dependent cellular damage, repair, and killing of red bone marrow cells. This system of differential equations is solved analytically through the use of a matrix approach for continuous and fractionated irradiations. The analytic solutions are confirmed through the dynamical solution of the model equations using SIMULINK. Rate coefficients describing the cellular processes of radiation damage and repair, extrapolated to humans from animal data sets and adjusted for neutron-gamma mixed fields, are employed in a SIMULINK analysis of criticality accidents. The results show that, for the time structures which may occur in criticality accidents, cell survival is established mainly by the average dose and dose rate.

  13. Isolation, characterization, and biologic features of bone marrow endothelial cells.

    PubMed

    Almeida-Porada, G; Ascensão, J L

    1996-10-01

    Bone marrow endothelial cells (BMECs) are an integral part of the bone marrow microenvironment and are likely to play an important role in the regulation of hematopoiesis, either by producing growth factors or inhibitory cytokines or by displaying adhesion molecules that can interact with hematopoietic progenitors. In the present study we demonstrate the isolation, propagation, and characterization of BMECs with regard to morphology, growth characteristics, phenotype, and production of cytokines. Furthermore, we report the creation of a cell line with "BMEC-like" characteristics and compare the characteristics of primary BMEC cultures to those of the immortalized cell line. In addition, we demonstrate that BMECs are susceptible to infection by a laboratory strain of human cytomegalovirus (CMV), suggesting that CMV infection of endothelial cells in vivo could potentially play a role in the hematologic abnormalities observed during CMV infection.

  14. Bone marrow hypoplasia associated with fenbendazole administration in a dog.

    PubMed

    Gary, Anthony T; Kerl, Marie E; Wiedmeyer, Charles E; Turnquist, Susan E; Cohn, Leah A

    2004-01-01

    A 1.5-year-old Doberman pinscher was presented with sudden-onset of fever and malaise. Twelve days prior to presentation, fenbendazole therapy was initiated for a suspected lungworm infection. Results of a complete blood count on presentation showed pancytopenia, while histopathological evaluation of a bone marrow core sample revealed bone marrow hypoplasia of undetermined etiology. Bactericidal antibiotics and fluid therapy, as well as discontinuation of fenbendazole administration, led to a complete resolution of clinical and hematological abnormalities within 15 days. An idiosyncratic reaction to fenbendazole was suspected based on the absence of infectious, neoplastic, autoimmune, and toxic etiologies, as well as resolution of clinical signs and pancytopenia upon drug withdrawal.

  15. Haemopoietic recovery in spleen and marrow after transplantation of bone marrow from either normal or hydroxyurea treated mice.

    PubMed

    Hasthorpe, S; Hodgson, G S

    1977-09-01

    Haemopoietic regeneration was studied following x-irradiation and transplantation of bone marrow from either normal or hydroxyurea-treated donor mice, to ascertain the contribution of proliferating progenitor cells to regeneration. With transplantation of equivalent numbers of CFU-S, total DNA and 3HTdR uptake into DNA in spleen and femoral bone marrow and the erythroid, granulocytic and mononuclear cell populations were not significantly different between normal (NBM) and hydroxyurea-treated (HUBM) marrow. The response of hypertransfused x-irradiated mice to erythropoietin (EPO) administration was also not significantly different in spleens of mice receiving normal or hydroxyurea-treated marrow.

  16. Collagen-containing scaffolds enhance attachment and proliferation of non-cultured bone marrow multipotential stromal cells.

    PubMed

    El-Jawhari, Jehan J; Sanjurjo-Rodríguez, Clara; Jones, Elena; Giannoudis, Peter V

    2016-04-01

    Large bone defects are ideally treated with autografts, which have many limitations. Therefore, osteoconductive scaffolds loaded with autologous bone marrow (BM) aspirate are increasingly used as alternatives. The purpose of this study was to compare the growth of multipotential stromal cells (MSCs) from unprocessed BM on a collagen-containing bovine bone scaffold (Orthoss(®) Collagen) with a non-collagen-containing bovine bone scaffold, Orthoss(®) . Another collagen-containing synthetic scaffold, Vitoss(®) was included in the comparison. Colonization of scaffolds by BM MSCs (n = 23 donors) was evaluated using microscopy, colony forming unit-fibroblast assay and flow-cytometry. The number of BM MSCs initially attached to Orthoss(®) Collagen and Vitoss(®) was similar but greater than Orthoss(®) (p = 0.001 and p = 0.041, respectively). Furthermore, the number of MSCs released from Orthoss(®) Collagen and Vitoss(®) after 2-week culture was also higher compared to Orthoss(®) (p = 0.010 and p = 0.023, respectively). Interestingly, collagen-containing scaffolds accommodated larger numbers of lymphocytic and myelomonocytic cells. Additionally, the proliferation of culture-expanded MSCs on Orthoss(®) collagen and Vitoss(®) was greater compared to Orthoss(®) (p = 0.047 and p = 0.004, respectively). Collectively, collagen-containing scaffolds were superior in supporting the attachment and proliferation of MSCs when they were loaded with unprocessed BM aspirates. This highlights the benefit of collagen incorporation into bone scaffolds for use with autologous bone marrow aspirates as autograft substitutes.

  17. Collagen‐containing scaffolds enhance attachment and proliferation of non‐cultured bone marrow multipotential stromal cells

    PubMed Central

    El‐Jawhari, Jehan J.; Sanjurjo‐Rodríguez, Clara; Jones, Elena

    2015-01-01

    ABSTRACT Large bone defects are ideally treated with autografts, which have many limitations. Therefore, osteoconductive scaffolds loaded with autologous bone marrow (BM) aspirate are increasingly used as alternatives. The purpose of this study was to compare the growth of multipotential stromal cells (MSCs) from unprocessed BM on a collagen‐containing bovine bone scaffold (Orthoss® Collagen) with a non‐collagen‐containing bovine bone scaffold, Orthoss®. Another collagen‐containing synthetic scaffold, Vitoss® was included in the comparison. Colonization of scaffolds by BM MSCs (n = 23 donors) was evaluated using microscopy, colony forming unit‐fibroblast assay and flow‐cytometry. The number of BM MSCs initially attached to Orthoss® Collagen and Vitoss® was similar but greater than Orthoss® (p = 0.001 and p = 0.041, respectively). Furthermore, the number of MSCs released from Orthoss® Collagen and Vitoss® after 2‐week culture was also higher compared to Orthoss® (p = 0.010 and p = 0.023, respectively). Interestingly, collagen‐containing scaffolds accommodated larger numbers of lymphocytic and myelomonocytic cells. Additionally, the proliferation of culture‐expanded MSCs on Orthoss® collagen and Vitoss® was greater compared to Orthoss® (p = 0.047 and p = 0.004, respectively). Collectively, collagen‐containing scaffolds were superior in supporting the attachment and proliferation of MSCs when they were loaded with unprocessed BM aspirates. This highlights the benefit of collagen incorporation into bone scaffolds for use with autologous bone marrow aspirates as autograft substitutes. © 2015 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 34:597–606, 2016. PMID:26466765

  18. Bone Marrow-Derived Mesenchymal Stromal Cells from Patients with Sickle Cell Disease Display Intact Functionality.

    PubMed

    Stenger, Elizabeth O; Chinnadurai, Raghavan; Yuan, Shala; Garcia, Marco; Arafat, Dalia; Gibson, Greg; Krishnamurti, Lakshmanan; Galipeau, Jacques

    2017-01-26

    Hematopoietic cell transplantation (HCT) is the only cure for sickle cell disease (SCD), but engraftment remains challenging in patients lacking matched donors. Infusion of mesenchymal stromal cells (MSCs) at the time of HCT may promote hematopoiesis and ameliorate graft-versus-host disease. Experimental murine models suggest MSC major histocompatibility complex compatibility with recipient impacts their in vivo function, suggesting autologous MSCs could be superior to third-party MSCs for promoting HCT engraftment. Here we tested whether bone marrow (BM)-derived MSCs from SCD subjects have comparable functionality compared with MSCs from healthy volunteers. SCD MSC doubling time and surface marker phenotype did not differ significantly from non-SCD. Third-party and autologous (SCD) T cell proliferation was suppressed in a dose-dependent manner by all MSCs. SCD MSCs comparably expressed indoleamine-2,3-dioxygenase, which based on transwell and blocking experiments appeared to be the dominant immunomodulatory pathway. The expression of key genes involved in hematopoietic stem cell (HSC)-MSC interactions was minimally altered between SCD and non-SCD MSCs. Expression was, however, altered by IFN-γ stimulation, particularly CXCL14, CXCL26, CX3CL1, CKITL, and JAG1, indicating the potential to augment MSC expression by cytokine stimulation. These data demonstrate the feasibility of expanding BM-derived MSCs from SCD patients that phenotypically and functionally do not differ per International Society of Cell Therapy essential criteria from non-SCD MSCs, supporting initial evaluation (primarily for safety) of autologous MSCs to enhance haploidentical HSC engraftment in SCD.

  19. Primary cutaneous aspergillosis and idiopathic bone marrow aplasia*

    PubMed Central

    Furlan, Karina Colossi; Pires, Mario Cezar; Kakizaki, Priscila; Chartuni, Juliana Cabral Nunes; Valente, Neusa Yuriko Sakai

    2016-01-01

    We describe the case of a 9-year-old boy with idiopathic bone marrow aplasia and severe neutropenia, who developed skin ulcers under cardiac monitoring electrodes. The diagnosis of primary cutaneous aspergillosis was made after the second biopsy and culture. Imaging investigation did not reveal internal fungal infection. The child was treated, but did not improve and died 3 months after admission. The report highlights and discusses the preventable risk of aspergillus skin infection in immunocompromised patients. PMID:27438213

  20. Thymopoietic and Bone Marrow Response to Murine Pneumocystis Pneumonia▿

    PubMed Central

    Shi, Xin; Zhang, Ping; Sempowski, Gregory D.; Shellito, Judd E.

    2011-01-01

    CD4+ T cells play a key role in host defense against Pneumocystis infection. To define the role of naïve CD4+ T cell production through the thymopoietic response in host defense against Pneumocystis infection, Pneumocystis murina infection in the lung was induced in adult male C57BL/6 mice with and without prior thymectomy. Pneumocystis infection caused a significant increase in the number of CCR9+ multipotent progenitor (MPP) cells in the bone marrow and peripheral circulation, an increase in populations of earliest thymic progenitors (ETPs) and double negative (DN) thymocytes in the thymus, and recruitment of naïve and total CD4+ T cells into the alveolar space. The level of murine signal joint T cell receptor excision circles (msjTRECs) in spleen CD4+ cells was increased at 5 weeks post-Pneumocystis infection. In thymectomized mice, the numbers of naïve, central memory, and total CD4+ T cells in all tissues examined were markedly reduced following Pneumocystis infection. This deficiency of naïve and central memory CD4+ T cells was associated with delayed pulmonary clearance of Pneumocystis. Extracts of Pneumocystis resulted in an increase in the number of CCR9+ MPPs in the cultured bone marrow cells. Stimulation of cultured bone marrow cells with ligands to Toll-like receptor 2 ([TLR-2] zymosan) and TLR-9 (ODN M362) each caused a similar increase in CCR9+ MPP cells via activation of the Jun N-terminal protein kinase (JNK) pathway. These results demonstrate that enhanced production of naïve CD4+ T lymphocytes through the thymopoietic response and enhanced delivery of lymphopoietic precursors from the bone marrow play an important role in host defense against Pneumocystis infection. PMID:21343353

  1. [Functional activity of bone marrow-derived peptides (myelopeptides)].

    PubMed

    Mikhaĭlova, A A; Petrov, R V

    2009-12-01

    The review describes structure and functions of bone marrow-derived peptides (myelopeptides). The final biological effects of these endogenous bioregulators (antitumor, antiviral, anti-infectious, antileukemia etc.) are due to their immunocorrecting and differentiating activity. Myelopeptides are the integral parts of the immune homeostasis maintenance system. Nowadays, medical preparations with no side effects and natural mechanisms of action are being developed on the basis of synthesized myelopeptides.

  2. MR-Based Assessment of Bone Marrow Fat in Osteoporosis, Diabetes, and Obesity

    PubMed Central

    Cordes, Christian; Baum, Thomas; Dieckmeyer, Michael; Ruschke, Stefan; Diefenbach, Maximilian N.; Hauner, Hans; Kirschke, Jan S.; Karampinos, Dimitrios C.

    2016-01-01

    Bone consists of the mineralized component (i.e., cortex and trabeculae) and the non-mineralized component (i.e., bone marrow). Most of the routine clinical bone imaging uses X-ray-based techniques and focuses on the mineralized component. However, bone marrow adiposity has been also shown to have a strong linkage with bone health. Specifically, multiple previous studies have demonstrated a negative association between bone marrow fat fraction (BMFF) and bone mineral density. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are ideal imaging techniques for non-invasively investigating the properties of bone marrow fat. In the present work, we first review the most important MRI and MRS methods for assessing properties of bone marrow fat, including methodologies for measuring BMFF and bone marrow fatty acid composition parameters. Previous MRI and MRS studies measuring BMFF and fat unsaturation in the context of osteoporosis are then reviewed. Finally, previous studies investigating the relationship between bone marrow fat, other fat depots, and bone health in patients with obesity and type 2 diabetes are presented. In summary, MRI and MRS are powerful non-invasive techniques for measuring properties of bone marrow fat in osteoporosis, obesity, and type 2 diabetes and can assist in future studies investigating the pathophysiology of bone changes in the above clinical scenarios. PMID:27445977

  3. Bone marrow stromal stem cells: nature, biology, and potential applications.

    PubMed

    Bianco, P; Riminucci, M; Gronthos, S; Robey, P G

    2001-01-01

    Bone marrow stromal cells are progenitors of skeletal tissue components such as bone, cartilage, the hematopoiesis-supporting stroma, and adipocytes. In addition, they may be experimentally induced to undergo unorthodox differentiation, possibly forming neural and myogenic cells. As such, they represent an important paradigm of post-natal nonhematopoietic stem cells, and an easy source for potential therapeutic use. Along with an overview of the basics of their biology, we discuss here their potential nature as components of the vascular wall, and the prospects for their use in local and systemic transplantation and gene therapy.

  4. The bone marrow niche for haematopoietic stem cells

    PubMed Central

    Morrison, Sean J.; Scadden, David T.

    2015-01-01

    Preface Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a paradigm for understanding mammalian stem cells and their niches, yet the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Here we review progress in elucidating the location and cellular components of the HSC niche in the bone marrow. The niche is perivascular, created partly by mesenchymal stromal cells and endothelial cells and often, but not always, located near trabecular bone. Outstanding questions concern the cellular complexity of the niche, the role of the endosteum, and functional heterogeneity among perivascular microenvironments. PMID:24429631

  5. Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells.

    PubMed

    Cox, Charles S; Hetz, Robert A; Liao, George P; Aertker, Benjamin M; Ewing-Cobbs, Linda; Juranek, Jenifer; Savitz, Sean I; Jackson, Margaret L; Romanowska-Pawliczek, Anna M; Triolo, Fabio; Dash, Pramod K; Pedroza, Claudia; Lee, Dean A; Worth, Laura; Aisiku, Imoigele P; Choi, Huimahn A; Holcomb, John B; Kitagawa, Ryan S

    2017-04-01

    that correlated with functional outcomes. Key inflammatory cytokines were downregulated. Treatment of severe, adult traumatic brain injury using an intravenously delivered autologous bone marrow mononuclear cell infusion is safe and logistically feasible. There appears to be a treatment signal as evidenced by central nervous system structural preservation, consistent with previous pediatric trial data. Inflammatory biomarkers are downregulated after cell infusion. Stem Cells 2016 Video Highlight: https://youtu.be/UiCCPIe-IaQ Stem Cells 2017;35:1065-1079.

  6. CNS Inflammation and Bone Marrow Neuropathy in Type 1 Diabetes

    PubMed Central

    Hu, Ping; Thinschmidt, Jeffrey S.; Yan, Yuanqing; Hazra, Sugata; Bhatwadekar, Ashay; Caballero, Sergio; Salazar, Tatiana; Miyan, Jaleel A.; Li, Wencheng; Derbenev, Andrei; Zsombok, Andrea; Tikhonenko, Maria; Dominguez, James M.; McGorray, Susan P.; Saban, Daniel R.; Boulton, Michael E.; Busik, Julia V.; Raizada, Mohan K.; Chan-Ling, Tailoi; Grant, Maria B.

    2014-01-01

    By using pseudorabies virus expressing green fluorescence protein, we found that efferent bone marrow–neural connections trace to sympathetic centers of the central nervous system in normal mice. However, this was markedly reduced in type 1 diabetes, suggesting a significant loss of bone marrow innervation. This loss of innervation was associated with a change in hematopoiesis toward generation of more monocytes and an altered diurnal release of monocytes in rodents and patients with type 1 diabetes. In the hypothalamus and granular insular cortex of mice with type 1 diabetes, bone marrow–derived microglia/macrophages were activated and found at a greater density than in controls. Infiltration of CD45+/CCR2+/GR-1+/Iba-1+ bone marrow–derived monocytes into the hypothalamus could be mitigated by treatment with minocycline, an anti-inflammatory agent capable of crossing the blood-brain barrier. Our studies suggest that targeting central inflammation may facilitate management of microvascular complications. PMID:24160325

  7. The in situ mechanics of trabecular bone marrow: the potential for mechanobiological response.

    PubMed

    Metzger, Thomas A; Kreipke, Tyler C; Vaughan, Ted J; McNamara, Laoise M; Niebur, Glen L

    2015-01-01

    Bone adapts to habitual loading through mechanobiological signaling. Osteocytes are the primary mechanical sensors in bone, upregulating osteogenic factors and downregulating osteoinhibitors, and recruiting osteoclasts to resorb bone in response to microdamage accumulation. However, most of the cell populations of the bone marrow niche,which are intimately involved with bone remodeling as the source of bone osteoblast and osteoclast progenitors, are also mechanosensitive. We hypothesized that the deformation of trabecular bone would impart mechanical stress within the entrapped bone marrow consistent with mechanostimulation of the constituent cells. Detailed fluid-structure interaction models of porcine femoral trabecular bone and bone marrow were created using tetrahedral finite element meshes. The marrow was allowed to flow freely within the bone pores, while the bone was compressed to 2000 or 3000 microstrain at the apparent level.Marrow properties were parametrically varied from a constant 400 mPas to a power law rule exceeding 85 Pas. Deformation generated almost no shear stress or pressure in the marrow for the low viscosity fluid, but exceeded 5 Pa when the higher viscosity models were used. The shear stress was higher when the strain rate increased and in higher volume fraction bone. The results demonstrate that cells within the trabecular bone marrow could be mechanically stimulated by bone deformation, depending on deformation rate, bone porosity, and bone marrow properties. Since the marrow contains many mechanosensitive cells, changes in the stimulatory levels may explain the alterations in bone marrow morphology with aging and disease, which may in turn affect the trabecular bone mechanobiology and adaptation.

  8. [Effect of aclacinomycin A on bone marrow (author's transl)].

    PubMed

    Ohmori, K; Shirai, M; Kiyosaki, T; Hori, S; Tone, H

    1980-04-01

    Japan White rabbits were treated with aclacinomycin A, a new anthracycline antitumor antibiotic, at a dose of 6.25 or 25.0 mg/kg by single intravenous, or 12.5 or 50.0 mg/kg by single oral administration, respectively. Beagle dogs were treated at a dose of 3.0 or 6.0 mg/kg by single intravenous injection. In rabbits in higher dose groups, RBC and WBC counts as well as lymphocyte ratio in peripheral blood decreased on day 1. Nucleated cell counts and erythroid elements in bone marrow decreased to raise M/E ratio (Myeloid/Erythroid ratio) on day 3. In a dog given at 6.0 mg/kg, WBC and platelet counts, lymphocyte and neutrocyte per cents in peripheral blood and also nucleated cells, particularly erythroid elements in bone marrow remarkably decreased on day 3 accompanied with an increase in M/E ratio. These changes were almost completely recovered by day 14 in both animals. No abnormalities were found in lower dose groups. Male Wistar rats, treated with the drug at a dose of 1.5 mg/kg by daily intraperitoneal injection for 30 days, showed slight decreases in peripheral WBC and RBC counts and M/E ratio in bone marrow. No change was observed in rats treated at 0.75 mg/kg and less for 30 days.

  9. Effect of cyclophosphamide and electromagnetic fields on mouse bone marrow

    SciTech Connect

    Cadossi, R.; Zucchini, P.; Emilia, G.; Torelli, G. )

    1990-02-26

    The authors have previously shown that the exposure to low frequency pulsing electromagnetic fields (PEMF) of mice X-ray irradiated resulted in an increased damage to the bone marrow. The series of experiments here reported were designed to investigate the effect of PEMF exposure after intraperitoneum injection of 200mg/kg of cyclophosphamide (CY). Control mice were CY injected only; experimental mice were CY injected and then exposed to PEMF. Exposure to PEMF (24 hours/day) increased the rate of decline of white blood cells in peripheral blood. Spleen weight was statistically higher among control mice than among mice exposed to PEMF at day 6, 8 and 10 after CY injection. Spleen autoradiography proved to be higher among PEMF exposed mice than among controls at day 8 and 9 after CY injection. The grafting efficiency of the bone marrow obtained from control mice was higher than the grafting efficiency of the bone marrow recovered from mice exposed to PEMF. All these data indicate that the exposure to PEMF increases the cytotoxic effect of CY.

  10. Bone Marrow Stem Cell Contribution to Pulmonary Homeostasis and Disease

    PubMed Central

    McDonald, Lindsay T; LaRue, Amanda C

    2015-01-01

    The understanding of bone marrow stem cell plasticity and contribution of bone marrow stem cells to pathophysiology is evolving with the advent of innovative technologies. Recent data has led to new mechanistic insights in the field of mesenchymal stem cell (MSC) research, and an increased appreciation for the plasticity of the hematopoietic stem cell (HSC). In this review, we discuss current research examining the origin of pulmonary cell types from endogenous lung stem and progenitor cells as well as bone marrow-derived stem cells (MSCs and HSCs) and their contributions to lung homeostasis and pathology. We specifically highlight recent findings from our laboratory that demonstrate an HSC origin for pulmonary fibroblasts based on transplantation of a clonal population of cells derived from a single HSC. These findings demonstrate the importance of developing an understanding of the sources of effector cells in disease state. Finally, a perspective is given on the potential clinical implications of these studies and others addressing stem cell contributions to lung tissue homeostasis and pathology. PMID:26798846

  11. FANCD2 protects against bone marrow injury from ferroptosis.

    PubMed

    Song, Xinxin; Xie, Yangchun; Kang, Rui; Hou, Wen; Sun, Xiaofang; Epperly, Michael W; Greenberger, Joel S; Tang, Daolin

    2016-11-18

    Bone marrow injury remains a serious concern in traditional cancer treatment. Ferroptosis is an iron- and oxidative-dependent form of regulated cell death that has become part of an emerging strategy for chemotherapy. However, the key regulator of ferroptosis in bone marrow injury remains unknown. Here, we show that Fanconi anemia complementation group D2 (FANCD2), a nuclear protein involved in DNA damage repair, protects against ferroptosis-mediated injury in bone marrow stromal cells (BMSCs). The classical ferroptosis inducer erastin remarkably increased the levels of monoubiquitinated FANCD2, which in turn limited DNA damage in BMSCs. FANCD2-deficient BMSCs were more sensitive to erastin-induced ferroptosis (but not autophagy) than FANCD2 wild-type cells. Knockout of FANCD2 increased ferroptosis-associated biochemical events (e.g., ferrous iron accumulation, glutathione depletion, and malondialdehyde production). Mechanically, FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4). Collectively, these findings indicate that FANCD2 plays a novel role in the negative regulation of ferroptosis. FANCD2 could represent an amenable target for the development of novel anticancer therapies aiming to reduce the side effects of ferroptosis inducers.

  12. Mobilised bone marrow-derived cells accelerate wound healing.

    PubMed

    Wang, Yu; Sun, Yu; Yang, Xiao-Yan; Ji, Shi-Zhao; Han, Shu; Xia, Zhao-Fan

    2013-08-01

    Massive skin defects caused by severe burn and trauma are a clinical challenge to surgeons. Timely and effective wound closure is often hindered by the lack of skin donor site. Bone marrow-derived cells (BMDCs) have been shown to 'differentiate' into multiple tissue cells. In this study we focused on the direct manipulation of endogenous BMDCs, avoiding the immunocompatibility issues and complicated cell isolation, purification, identification and amplification procedures in vitro on wound repair. We found that mobilisation of the BMDCs into the circulation significantly increased the amount of BMDCs at the injury site which in turn accelerated healing of large open wound. We used a chimeric green fluorescent protein (GFP) mouse model to track BMDCs and to investigate their role in full-thickness skin excisional wounds. We have shown that bone marrow mobilisation by granulocyte colony stimulating factor (G-CSF) exerted multiple beneficial effects on skin repair, both by increasing the engraftment of BMDCs into the skin to differentiate into multiple skin cell types and by upregulating essential cytokine mRNAs critical to wound repair. The potential trophic effects of G-CSF on bone marrow stem cells to accelerate wound healing could have a significant clinical impact.

  13. Bone Marrow Microenvironment Modulation of Acute Lymphoblastic Leukemia Phenotype

    PubMed Central

    Moses, Blake S; Slone, William L; Thomas, Patrick; Evans, Rebecca; Piktel, Debbie; Angel, Peggi M; Walsh, Callee M; Cantrell, Pamela S; Rellick, Stephanie L; Martin, Karen H; Simpkins, James W; Gibson, Laura F

    2015-01-01

    Acute lymphoblastic leukemia (ALL) treatment regimens have dramatically improved the survival of ALL patients. However, chemoresistant minimal residual disease (MRD) that persists following cessation of therapy contributes to aggressive relapse. The bone marrow microenvironment (BMM) is an established “site of sanctuary” for ALL as well as myeloid lineage hematopoietic disease, with signals in this unique anatomical location contributing to drug resistance. Several models have been developed to recapitulate the interactions between the BMM and ALL cells. However, many in vitro models fail to accurately reflect the level of protection afforded to the most resistant sub-set of leukemic cells during co-culture with BMM elements. Pre-clinical in vivo models have advantages, but can be costly, and are often not fully informed by optimal in vitro studies. In the current report we describe an innovative extension of 2D co-culture wherein ALL cells uniquely interact with bone marrow derived stromal cells. Tumor cells in this model bury beneath primary human bone marrow derived stromal cells or osteoblasts, termed “phase dim” (PD) ALL, and exhibit a unique phenotype characterized by altered metabolism, distinct protein expression profiles, increased quiescence, and pronounced chemotherapy resistance. Investigation focused on the PD subpopulation may more efficiently inform pre-clinical design and investigation of MRD and relapse that arises from BMM supported leukemic tumor cells. PMID:26407636

  14. Bone marrow-derived cells are present in Mooren's ulcer.

    PubMed

    Ye, Juan; Chen, Jian; Kim, Jae Chan; Yao, Ke

    2004-01-01

    To investigate whether bone marrow-derived cells are present in Mooren's ulcer and involved in its destructive and regenerative disease course, tissue specimens were collected from 3 eyes of 3 patients with Mooren's ulcer that underwent lamellar keratectomy. Three normal donor limbal corneoscleras served as controls. Immunohistochemical staining patterns were analyzed by using the following antibodies: CD34 (a marker of hematopoietic progenitor cells and endothelium), c-kit (a marker of hematopoietic and stromal progenitor cells) and STRO-1 (a differentiation antigen present on bone marrow fibroblast cells and on various nonhematopoietic progenitor cells). Strong positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens, especially in the superficial stroma. A few weakly expressed CD34 stromal cells were seen in normal limbal cornea, but no immunoreactivity for c-kit and STRO-1 was found. Bone marrow-derived cells are present in Mooren's ulcer and contribute to its destructive and regeneration process by synergizing with other factors. Specific therapeutic strategies that target the role of these cells in Mooren's ulcer are anticipated.

  15. T2 vertebral bone marrow changes after space flight

    NASA Technical Reports Server (NTRS)

    LeBlanc, A.; Lin, C.; Evans, H.; Shackelford, L.; Martin, C.; Hedrick, T.

    1999-01-01

    Bone biopsies indicate that during immobilization bone marrow adipose tissue increases while the functional cellular fraction decreases. One objective of our Spacelab flight experiment was to determine, using in vivo volume-localized magnetic resonance spectroscopy (VLMRS), whether bone marrow composition was altered by space flight. Four crew members of a 17 day Spacelab mission participated in the experiment. The apparent cellular fraction and transverse relaxation time (T2) were determined twice before launch and at several times after flight. Immediately after flight, no significant change in the cellular fraction was found. However, the T2 of the cellular, but not the fat component increased following flight, although to a variable extent, in all crew members with a time course for return to baseline lasting several months. The T2 of seven control subjects showed no significant change. Although these observations may have several explanations, it is speculated that the observed T2 changes might reflect increased marrow osteoblastic activity during recovery from space flight.

  16. Intravitreal Injection of Bone Marrow Mesenchymal Stem Cells in Patients with Advanced Retinitis Pigmentosa; a Safety Study

    PubMed Central

    Satarian, Leila; Nourinia, Ramin; Safi, Sare; Kanavi, Mozhgan Rezaei; Jarughi, Neda; Daftarian, Narsis; Arab, Leila; Aghdami, Nasser; Ahmadieh, Hamid; Baharvand, Hossein

    2017-01-01

    Purpose: To examine the safety of a single intravitreal injection of autologous bone Marrow Mesenchymal stem cells (MSCs) in patients with advanced retinitis pigmentosa (RP). Methods: A prospective, phase I, nonrandomized, open-label study was conducted on 3 eyes of 3 volunteers with advanced RP. Visual acuity, slit-lamp examination, fundus examination, optical coherence tomography, fundus auto-fluorescence, fluorescein angiography and multifocal electroretinography were performed before and after an intravitreal injection of approximately one-million MSCs. The patients were followed for one year. Further evaluation of MSCs was performed by injection of these cells into the mouse vitreous cavity. Results: No, adverse events were observed in eyes of 2 out of 3 patients after transplantation of MSCs. These patients reported improvements in perception of the light after two weeks, which lasted for 3 months. However, severe fibrous tissue proliferation was observed in the vitreous cavity and retrolental space of the third patient's eye, which led to tractional retinal detachment (TRD), iris neovascularization and formation of mature cataract. Injection of this patient's MSCs into the vitreous cavity of mice also resulted in fibrosis; however, intravitreal injections of the two other patients' cells into the mouse vitreous did not generate any fibrous tissue. Conclusion: Intravitreal injection of autologous bone marrow MSCs into patients' eyes with advanced RP does not meet safety standards. Major side effects of this therapy can include fibrosis and TRD. We propose thorough evaluation of MSCs prior to transplantation by intravitreal injection in the laboratory animals.\\ PMID:28299008

  17. Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

    PubMed Central

    Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

    2016-01-01

    Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

  18. Comparison of solid and fluid constitutive models of bone marrow during trabecular bone compression.

    PubMed

    Metzger, Thomas A; Niebur, Glen L

    2016-10-03

    The mechanical environment and mechanobiology of bone marrow may play essential roles in bone adaptation, cancer metastasis, and immune cell regulation. However, the location of marrow within the trabecular pore space complicates experimental measurement of marrow mechanics. Computational models provide a means to assess the shear stress and pressure in the marrow during physiological loading, but they rely on accurate inputs for the marrow and the physics assumed for the interaction of bone and marrow. Elastic, viscoelastic, and fluid constitutive properties have all been reported from experimental measurements of marrow properties. It is unclear whether this ambiguity reflects the various length-scales, loading rates, and boundary conditions of the experiments, or if the material models are sufficiently similar as to be interchangeable. To address this question, we analyzed both the mean shear stress and its spatial distribution induced in marrow during compression of trabecular bone cubes when using linear elastic, neo-Hookean, viscoelastic, and power-law fluid constitutive models. Experimentally reported parameters were initially applied for all four constitutive models, resulting in poor agreement. The parameters of the soft solid models were calibrated by linear interpolation so that the volume averaged shear stress agreed with the fluid model for each, but this could only be accomplished on a specimen-by-specimen basis. Following calibration, the root-mean-squared (RMS) difference between the solid and fluid constitutive models was still greater than 26% even when the overall mean shear stress was in close agreement, indicating that the spatial distribution of stress is also sensitive to the constitutive model. As such, the choice of constitutive model should be backed by a strong rationale, and results should be interpreted with care.

  19. An Exploratory Clinical Trial for Idiopathic Osteonecrosis of Femoral Head by Cultured Autologous Multipotent Mesenchymal Stromal Cells Augmented with Vascularized Bone Grafts

    PubMed Central

    Aoyama, Tomoki; Goto, Koji; Kakinoki, Ryosuke; Ikeguchi, Ryosuke; Ueda, Michiko; Kasai, Yasunari; Maekawa, Taira; Tada, Harue; Teramukai, Satoshi; Nakamura, Takashi

    2014-01-01

    Idiopathic osteonecrosis of femoral head (ION) is a painful disorder that progresses to collapse of the femoral head and destruction of the hip joint. Although its precise pathology remains unknown, the loss of blood supply causing the loss of living bone-forming cells is a hallmark of the pathophysiology of osteonecrosis. Transplantation of multipotent mesenchymal stromal cells (MSCs) is a promising tool for regenerating the musculoskeletal system. The aim of the present study was to assess the safety and efficacy of transplantation of cultured autologous bone marrow-derived MSCs mixed with β-tricalcium phosphate (β-TCP) in combination with vascularized bone grafts for the treatment of advanced stage ION in a clinical trial. Ten patients with stage 3 ION were enrolled in this study. Autologous bone marrow-derived MSCs were cultured with autologous serum, and cells (0.5–1.0×108) were transplanted after mixing with β-TCP granules in combination with vascularized iliac bone grafts. Patients were assessed 24 months after treatment. The primary and secondary endpoints were progression of the radiological stage and changes in bone volume at the femoral head, and clinical score, respectively. Nine of ten patients completed the protocol, seven of whom remained at stage 3, and the remaining two cases progressed to stage 4. The average bone volume increased from 56.5±8.5 cm3 to 57.7±10.6 cm3. The average clinical score according to the Japan Orthopaedic Association improved from 65.6±25.5 points to 87.9±19.0 points. One severe adverse event was observed, which was not related to the clinical trial. Although the efficacy of cell transplantation was still to be determined, all procedures were successfully performed and some young patients with extensive necrotic lesions with pain demonstrated good bone regeneration with amelioration of symptoms. Further improvements in our method using MSCs and the proper selection of patients will open a new approach for the

  20. Bone marrow adsorbed dose of rhenium-186-HEDP and the relationship with decreased platelet counts

    SciTech Connect

    Klerk, J.M.H. de; Dieren, E.B. van; Schip, A.D. van het

    1996-01-01

    Rhenium-186(Sn)-1,1-hydroxyethylidene diphosphonate ({sup 186}Re-HEDP) has been used for palliation of metastatic bone pain. The purpose of this study was to find a relationship between the bone marrow absorbed dose and the toxicity, expressed as the percentage decrease in the peripheral blood platelet count. The bone marrow absorbed dose was calculated according to the MIRD model using data obtained from ten treatments of patients suffering from metastatic prostate cancer; noninvasive and pharmacokinetic method were used. The bone marrow doses were related to toxicity using the pharmacodynamic sigmoid E{sub max} model. The mean bone marrow absorbed doses using the noninvasive and pharmacokinetic methods were in a close range to each other (1.07 mGy/MBq and 1.02 mGy/MBq, respectively). There was a good relationship between the toxicity and the bone marrow absorbed dose (r = 0.80). Furthermore, the EDrm{sub 50} (i.e., the bone marrow absorbed dose producing a 50% platelet decrease) to bone marrow for {sup 186}Re-HEDP was on the order of 2 Gy. Although the function of normal bone marrow is affected by metastases in patients with metastatic bone disease, the MIRD model can be used to relate toxicity to the bone marrow absorbed dose after a therapeutic dosage of {sup 186}Re-HEDP. 33 refs., 1 fig., 1 tab.

  1. Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study.

    PubMed

    Chantry, Andrew D; Snowden, John A; Craddock, Charles; Peggs, Karl; Roddie, Claire; Craig, Jenny I O; Orchard, Kim; Towlson, Keiren E; Pearce, Rachel M; Marks, David I

    2006-12-01

    Relapsed acute myeloid leukemia (AML) in adults has a poor prognosis if treated with chemotherapy alone. Case series have previously supported the role of myeloablation and autologous transplantation as a potentially curative treatment. This study aimed to use the large numbers and extended follow-up data in the British Society of Blood and Marrow Transplantation (BSBMT) registry database to establish long-term outcomes and relate these to biological and procedural factors. The BSBMT registry database was used to retrospectively identify 152 adult patients (age, 16-69 years) with AML in second remission treated with autologous transplantation in 1982-2003. Cytogenetic data were available for 68% of the patients; of these, at diagnosis, 42% had good risk features, 57% had standard risk features, and 1% had poor risk features. Conditioning regimens varied; autologous rescue was provided with bone marrow (BM) (71%), peripheral blood stem cells (PBSCs) (18%), or both (11%), which were harvested during first complete remission (CR1) and/or second CR (CR2). Median follow-up was 84 months (range, 2-200 months). At 10 years, actuarial overall survival (OS) was 32%, progression-free survival (PFS) was 28%, and relapse rate (RR) was 57%. The 100-day nonrelapse mortality (NRM) was 7%, rising to 11% at 1 year and to 14% at 10 years. OS was significantly related to M3 subtype (5-year OS, 66%; P = .005), patient age at diagnosis (P = .005) and transplantation (P = .026), and length of CR1, with greatest significance if the patient was dichotomized at CR1 duration of < 8 months or > or = 8 months (P = .0001). There was no difference in OS between regimens containing total body irradiation (TBI) and chemotherapy alone (P = .7). In relation to the nature of autologous graft material, there was improved OS (P = .025) and PFS (P = .009) with the use of cells harvested entirely in CR1 compared with cells harvested in CR2 or in both CR1 and CR2. Engraftment times were significantly

  2. Bone Marrow Stem Cells Added to a Hydroxyapatite Scaffold Result in Better Outcomes after Surgical Treatment of Intertrochanteric Hip Fractures

    PubMed Central

    Gutierres, Manuel; Lopes, M. Ascenção; Santos, J. Domingos; Cabral, A. T.; Pinto, R.

    2014-01-01

    Introduction. Intertrochanteric hip fractures occur in the proximal femur. They are very common in the elderly and are responsible for high rates of morbidity and mortality. The authors hypothesized that adding an autologous bone marrow stem cells concentrate (ABMC) to a hydroxyapatite scaffold and placing it in the fracture site would improve the outcome after surgical fixation of intertrochanteric hip fractures. Material and Methods. 30 patients were randomly selected and divided into 2 groups of 15 patients, to receive either the scaffold enriched with the ABMC (Group A) during the surgical procedure, or fracture fixation alone (Group B). Results. There was a statistically significant difference in favor of group A at days 30, 60, and 90 for Harris Hip Scores (HHS), at days 30 and 60 for VAS pain scales, for bedridden period and time taken to start partial and total weight bearing (P < 0.05). Discussion. These results show a significant benefit of adding a bone marrow enriched scaffold to surgical fixation in intertrochanteric hip fractures, which can significantly reduce the associated morbidity and mortality rates. Conclusion. Bone marrow stem cells added to a hydroxyapatite scaffold result in better outcomes after surgical treatment of intertrochanteric hip fractures. PMID:24955356

  3. Generation of clinical grade human bone marrow stromal cells for use in bone regeneration.

    PubMed

    Robey, Pamela G; Kuznetsov, Sergei A; Ren, Jiaqiang; Klein, Harvey G; Sabatino, Marianna; Stroncek, David F

    2015-01-01

    In current orthopaedic practice, there is a need to increase the ability to reconstruct large segments of bone lost due to trauma, resection of tumors and skeletal deformities, or when normal regenerative processes have failed such as in non-unions and avascular necrosis. Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells), when used in conjunction with appropriate carriers, represent a means by which to achieve bone regeneration in such cases. While much has been done at the bench and in pre-clinical studies, moving towards clinical application requires the generation of clinical grade cells. What is described herein is an FDA-approved cell manufacturing procedure for the ex vivo expansion of high quality, biologically active human BMSCs. This article is part of a Special Issue entitled Stem Cells and Bone.

  4. Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow.

    PubMed

    Park, Min Hee; Jin, Hee Kyung; Min, Woo-Kie; Lee, Won Woo; Lee, Jeong Eun; Akiyama, Haruhiko; Herzog, Herbert; Enikolopov, Grigori N; Schuchman, Edward H; Bae, Jae-sung

    2015-06-12

    Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY-deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy-induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide.

  5. Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow

    PubMed Central

    Park, Min Hee; Jin, Hee Kyung; Min, Woo-Kie; Lee, Won Woo; Lee, Jeong Eun; Akiyama, Haruhiko; Herzog, Herbert; Enikolopov, Grigori N; Schuchman, Edward H; Bae, Jae-sung

    2015-01-01

    Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY-deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy-induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide. PMID:25916827

  6. On a mathematical model of bone marrow metastatic niche.

    PubMed

    Munoz, Ana Isabel; Tello, J Ignacio

    2017-02-01

    We propose a mathematical model to describe tumor cells movement towards a metastasis location into the bone marrow considering the influence of chemotaxis inhibition due to the action of a drug. The model considers the evolution of the signaling molecules CXCL-12 secreted by osteoblasts (bone cells responsible of the mineralization of the bone) and PTHrP (secreted by tumor cells) which activates osteoblast growth. The model consists of a coupled system of second order PDEs describing the evolution of CXCL-12 and PTHrP, an ODE of logistic type to model the Osteoblasts density and an extra equation for each cancer cell. We also simulate the system to illustrate the qualitative behavior of the solutions. The numerical method of resolution is also presented in detail.

  7. Erythropoietic bone marrow in the pigeon: Development of its distribution and volume during growth and pneumatization of bones

    SciTech Connect

    Schepelmann, K. )

    1990-01-01

    During postnatal development of the pigeon, a large portion of the skeleton becomes pneumatized, displacing the hemopoietic bone marrow. The consequences of pneumatization on distribution and quantity of bone marrow as well as the availability of other sites for hemopoiesis have been investigated. Hemopoietic marrow of differently aged pigeons divided into five groups from 1 week posthatching (p.h.) up to 6 months p.h. was labeled with Fe-59 and examined by serial whole-body sections. Autoradiography and morphometry as well as scintillation counts of single bones and organs were also carried out. No sign of a reactivation of embryonic sites of erythropoiesis was found. Bone marrow weight and its proportion of whole-body weight increased during the first 4 weeks p.h. from 0.54% to 2.44% and decreased in the following months to about 1.0%. The developing bone marrow showed a progressive distribution during the first months of life, eventually being distributed proportionally over the entire skeleton, except for the skull. At the age of 6 months p.h. bone marrow had been displaced, its volume decreasing in correlation to increasing pneumaticity and conversion to fatty marrow. This generates the characteristic pattern of bone marrow distribution in adult pigeons, which shows hemopoietic bone marrow in ulna, radius, femur, tibiotarsus, scapula, furcula, and the caudal vertebrae.

  8. The use of bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for alveolar bone tissue engineering: basic science to clinical translation.

    PubMed

    Kagami, Hideaki; Agata, Hideki; Inoue, Minoru; Asahina, Izumi; Tojo, Arinobu; Yamashita, Naohide; Imai, Kohzoh

    2014-06-01

    Bone tissue engineering is a promising field of regenerative medicine in which cultured cells, scaffolds, and osteogenic inductive signals are used to regenerate bone. Human bone marrow stromal cells (BMSCs) are the most commonly used cell source for bone tissue engineering. Although it is known that cell culture and induction protocols significantly affect the in vivo bone forming ability of BMSCs, the responsible factors of clinical outcome are poorly understood. The results from recent studies using human BMSCs have shown that factors such as passage number and length of osteogenic induction significantly affect ectopic bone formation, although such differences hardly affected the alkaline phosphatase activity or gene expression of osteogenic markers. Application of basic fibroblast growth factor helped to maintain the in vivo osteogenic ability of BMSCs. Importantly, responsiveness of those factors should be tested under clinical circumstances to improve the bone tissue engineering further. In this review, clinical application of bone tissue engineering was reviewed with putative underlying mechanisms.

  9. Role of immobilization of irradiated rats in the protective effect of bone marrow shielding

    NASA Technical Reports Server (NTRS)

    Gronskaya, N. F.; Strelin, G. S.

    1982-01-01

    Rats were exposed to X-radiation to study the influence of immobilization and shielding of part of bone marrow during exposure on survival. It is concluded that (1) the beneficial effect of the stress factor (created by the immobilization of rats during exposure) can aggregate with the effect of bone marrow shielding and, under certain conditions, imitate the latter; and (2) the probability of the protective effect of immobilization should be taken into account when assessing the influence of bone marrow shielding.

  10. [Bone metabolism and cardiovascular function update. Inter-communication between bone marrow hematopoiesis and skeletal/vascular network].

    PubMed

    Katayama, Yoshio

    2014-07-01

    The hematopoiesis takes place in the bone marrow. Because bone marrow is the "marrow" of the bone, bone marrow does not exist without bone. The specialized microenvironment for hematopoietic stem cells (HSCs) to be appropriately functional is called "niche" . In the recent ten years since the bone-forming osteoblast was identified as a HSC niche, the entire mesenchymal lineage cells from mesenchymal stem cells to end-terminal osteocytes have been recognized as niche cells or niche-modulators. Among these, mesenchymal stem/progenitor cells are located at perivascular area. The very recent study showed the difference between arteriolar and sinusoidal niches. It is likely that the vascular network and the bone tissue are connected by the mesenchymal lineage cells as a complex of bone forming system, and HSCs utilize this complex as a series of niche.

  11. The bone marrow microenvironment contributes to type I diabetes induced osteoblast death.

    PubMed

    Coe, Lindsay M; Irwin, Regina; Lippner, Dennean; McCabe, Laura R

    2011-02-01

    Type I diabetes increases an individual's risk for bone loss and fracture, predominantly through suppression of osteoblast activity (bone formation). During diabetes onset, levels of blood glucose and pro-inflammatory cytokines (including tumor necrosis factor α (TNFα)) increased. At the same time, levels of osteoblast markers are rapidly decreased and stay decreased chronically (i.e., 40 days later) at which point bone loss is clearly evident. We hypothesized that early bone marrow inflammation can promote osteoblast death and hence reduced osteoblast markers. Indeed, examination of type I diabetic mouse bones demonstrates a greater than twofold increase in osteoblast TUNEL staining and increased expression of pro-apoptotic factors. Osteoblast death was amplified in both pharmacologic and spontaneous diabetic mouse models. Given the known signaling and inter-relationships between marrow cells and osteoblasts, we examined the role of diabetic marrow in causing the osteoblast death. Co-culture studies demonstrate that compared to control marrow cells, diabetic bone marrow cells increase osteoblast (MC3T3 and bone marrow derived) caspase 3 activity and the ratio of Bax/Bcl-2 expression. Mouse blood glucose levels positively correlated with bone marrow induced osteoblast death and negatively correlated with osteocalcin expression in bone, suggesting a relationship between type I diabetes, bone marrow and osteoblast death. TNF expression was elevated in diabetic marrow (but not co-cultured osteoblasts); therefore, we treated co-cultures with TNFα neutralizing antibodies. The antibody protected osteoblasts from bone marrow induced death. Taken together, our findings implicate the bone marrow microenvironment and TNFα in mediating osteoblast death and contributing to type I diabetic bone loss.

  12. Effect of nephrotoxic drugs on the development of radiation nephropathy after bone marrow transplantation

    SciTech Connect

    Lawton, C.A.; Fish, B.L.; Moulder, J.E. )

    1994-03-01

    Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy. Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests. Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy. Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy. 34 refs., 4 figs., 2 tabs.

  13. Necroptosis in spontaneously-mutated hematopoietic cells induces autoimmune bone marrow failure in mice

    PubMed Central

    Xin, Junping; Breslin, Peter; Wei, Wei; Li, Jing; Gutierrez, Rafael; Cannova, Joseph; Ni, Allen; Ng, Grace; Schmidt, Rachel; Chen, Haiyan; Parini, Vamsi; Kuo, Paul C.; Kini, Ameet R.; Stiff, Patrick; Zhu, Jiang; Zhang, Jiwang

    2017-01-01

    Acquired aplastic anemia is an autoimmune-mediated bone marrow failure syndrome. The mechanism by which such an autoimmune reaction is initiated is unknown. Whether and how the genetic lesions detected in patients cause autoimmune bone marrow failure have not yet been determined. We found that mice with spontaneous deletion of the TGFβ-activated kinase-1 gene in a small subset of hematopoietic cells developed bone marrow failure which resembled the clinical manifestations of acquired aplastic anemia patients. Bone marrow failure in such mice could be reversed by depletion of CD4+ T lymphocytes or blocked by knockout of interferon-γ, suggesting a Th1-cell-mediated autoimmune mechanism. The onset and progression of bone marrow failure in such mice were significantly accelerated by the inactivation of tumor necrosis factor-α signaling. Tumor necrosis factor-α restricts autoimmune bone marrow failure by inhibiting type-1 T-cell responses and maintaining the function of myeloid-derived suppressor cells. Furthermore, we determined that necroptosis among a small subset of mutant hematopoietic cells is the cause of autoimmune bone marrow failure because such bone marrow failure can be prevented by deletion of receptor interacting protein kinase-3. Our study suggests a novel mechanism to explain the pathogenesis of autoimmune bone marrow failure. PMID:27634200

  14. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury.

    PubMed

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-05-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 10(6) rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells.

  15. Use of impedance plethysmography to continually monitor bone marrow blood flow

    NASA Technical Reports Server (NTRS)

    Montgomery, L. D.; Mcewen, G. N., Jr.; Gerber, R. L.; Cann, C. E.; Morey, E. R.

    1984-01-01

    An impedance-plethysmographic technique is described which can be used to quantify temporal bone-marrow blood-flow changes. Results obtained with the impedance technique compare favorably with the data from simultaneously administered microspheres. Injection of sympathomimetic drugs produced measurable responses: isoproterenol caused a significant increase in bone-marrow blood flow within 1 min, and levarterenol decreased bone-marrow blood flow. Data obtained with impedance plethysmography suggest that the technique is feasible for multiple measurements on the same animal and that the technique can be used to study acute or chronic changes in bone-marrow blood flow following various experimental treatments.

  16. Muscle-specific kinase antibody associated myasthenia gravis after bone marrow transplantation.

    PubMed

    Heidarzadeh, Zeinab; Mousavi, Seyyed-Asadollah; Ostovan, Vahid Reza; Nafissi, Shahriar

    2014-02-01

    Myasthenia gravis is a rare complication of bone marrow transplantation and graft versus host disease. We report a 30-year-old woman presented with oculobulbar and proximal limb weakness after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Also, she developed graft versus host disease following bone marrow transplantation. Investigations led to the diagnosis of muscle specific kinase antibody related myasthenia gravis. There have been only two case reports of muscle specific kinase antibody positive myasthenia gravis after bone marrow transplantation in the literature, but none of the previously reported cases had graft versus host disease.

  17. Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients.

    PubMed

    Rettig, M B; Ma, H J; Vescio, R A; Põld, M; Schiller, G; Belson, D; Savage, A; Nishikubo, C; Wu, C; Fraser, J; Said, J W; Berenson, J R

    1997-06-20

    Kaposi's sarcoma-associated herpesvirus (KSHV) was found in the bone marrow dendritic cells of multiple myeloma patients but not in malignant plasma cells or bone marrow dendritic cells from normal individuals or patients with other malignancies. In addition the virus was detected in the bone marrow dendritic cells from two out of eight patients with monoclonal gammopathy of undetermined significance (MGUS), a precursor to myeloma. Viral interleukin-6, the human homolog of which is a growth factor for myeloma, was found to be transcribed in the myeloma bone marrow dendritic cells. KSHV may be required for transformation from MGUS to myeloma and perpetuate the growth of malignant plasma cells.

  18. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    PubMed Central

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells. PMID:25206912

  19. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    PubMed Central

    Li, Guihong; Yu, Fengbo; Lei, Ting; Gao, Haijun; Li, Peiwen; Sun, Yuxue; Huang, Haiyan; Mu, Qingchun

    2016-01-01

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research. PMID:27482235

  20. Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases.

    PubMed

    Hardaway, Aimalie L; Herroon, Mackenzie K; Rajagurubandara, Erandi; Podgorski, Izabela

    2014-09-01

    Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease.

  1. Successful treatment of a humeral capitulum osteonecrosis with bone morphogenetic protein-7 combined with autologous bone grafting.

    PubMed

    Marsell, Richard; Hailer, Nils P

    2014-08-01

    We present the case of a 27-year-old female with subcortical osteonecrosis of the humeral capitulum. Percutaneous retrograde drilling of the lesion and application of recombinant human bone morphogenetic protein (BMP)-7 were combined with autologous bone grafting. At follow-up the patient was almost pain-free, had normalized her range of motion, and radiography showed consolidation of the lesion without any heterotopic bone formation. By timing surgery prior to subchondral collapse, biomechanical stability of the subchondral bone was maintained. To our knowledge, this is the first report on the treatment of an osteonecrosis in this location with a BMP, and this strategy could potentially be applied in other locations with juxta-articular osteonecrosis.

  2. Osteoblastic Wnts differentially regulate bone remodeling and the maintenance of bone marrow mesenchymal stem cells.

    PubMed

    Wan, Yong; Lu, Cheng; Cao, Jingjing; Zhou, Rujiang; Yao, Yiyun; Yu, Jian; Zhang, Lingling; Zhao, Haixia; Li, Hanjun; Zhao, Jianzhi; Zhu, Xuming; He, Lin; Liu, Yongzhong; Yao, Zhengju; Yang, Xiao; Guo, Xizhi

    2013-07-01

    Wnt signaling has important roles in embryonic bone development and postnatal bone remodeling, but inconsistent impact on bone property is observed in different genetic alterations of Lrp5 and β-catenin. More importantly, it is still controversial whether Lrp5 regulate bone formation locally or globally through gut-derived serotonin. Here we explored the function of Wnt proteins in osteoblastic niche through inactivation of the Wntless (Wls) gene, which abrogates the secretion of Wnts. The depletion of Wls in osteoblast progenitor cells resulted in severe osteopenia with more profound defects in osteoblastogenesis, osteoclastogenesis and maintenance of bone marrow mesenchymal stem cells (BMSCs) compared to that observed in Lrp5 and β-catenin mutants. These findings support the point of view that Wnt/Lrp5 signaling locally regulates bone mass accrual through multiple effects of osteoblastic Wnts on osteoblastic bone formation and osteoclastic bone resorption. Moreover, osteoblastic Wnts confer a niche role for maintenance of BMSCs, providing novel cues for the definition of BMSCs niche in bone marrow.

  3. Dissecting the role of bone marrow stromal cells on bone metastases.

    PubMed

    Buenrostro, Denise; Park, Serk In; Sterling, Julie A

    2014-01-01

    Tumor-induced bone disease is a dynamic process that involves interactions with many cell types. Once metastatic cancer cells reach the bone, they are in contact with many different cell types that are present in the cell-rich bone marrow. These cells include the immune cells, myeloid cells, fibroblasts, osteoblasts, osteoclasts, and mesenchymal stem cells. Each of these cell populations can influence the behavior or gene expression of both the tumor cells and the bone microenvironment. Additionally, the tumor itself can alter the behavior of these bone marrow cells which further alters both the microenvironment and the tumor cells. While many groups focus on studying these interactions, much remains unknown. A better understanding of the interactions between the tumor cells and the bone microenvironment will improve our knowledge on how tumors establish in bone and may lead to improvements in diagnosing and treating bone metastases. This review details our current knowledge on the interactions between tumor cells that reside in bone and their microenvironment.

  4. Bone marrow derived stem cells in joint and bone diseases: a concise review.

    PubMed

    Marmotti, Antonio; de Girolamo, Laura; Bonasia, Davide Edoardo; Bruzzone, Matteo; Mattia, Silvia; Rossi, Roberto; Montaruli, Angela; Dettoni, Federico; Castoldi, Filippo; Peretti, Giuseppe

    2014-09-01

    Stem cells have huge applications in the field of tissue engineering and regenerative medicine. Their use is currently not restricted to the life-threatening diseases but also extended to disorders involving the structural tissues, which may not jeopardize the patients' life, but certainly influence their quality of life. In fact, a particularly popular line of research is represented by the regeneration of bone and cartilage tissues to treat various orthopaedic disorders. Most of these pioneering research lines that aim to create new treatments for diseases that currently have limited therapies are still in the bench of the researchers. However, in recent years, several clinical trials have been started with satisfactory and encouraging results. This article aims to review the concept of stem cells and their characterization in terms of site of residence, differentiation potential and therapeutic prospective. In fact, while only the bone marrow was initially considered as a "reservoir" of this cell population, later, adipose tissue and muscle tissue have provided a considerable amount of cells available for multiple differentiation. In reality, recently, the so-called "stem cell niche" was identified as the perivascular space, recognizing these cells as almost ubiquitous. In the field of bone and joint diseases, their potential to differentiate into multiple cell lines makes their application ideally immediate through three main modalities: (1) cells selected by withdrawal from bone marrow, subsequent culture in the laboratory, and ultimately transplant at the site of injury; (2) bone marrow aspirate, concentrated and directly implanted into the injury site; (3) systemic mobilization of stem cells and other bone marrow precursors by the use of growth factors. The use of this cell population in joint and bone disease will be addressed and discussed, analysing both the clinical outcomes but also the basic research background, which has justified their use for the

  5. [Distribution of compact bone mesenchymal stem cells in lung tissue and bone marrow of mouse].

    PubMed

    Wang, Rui-Ping; Wu, Ren-Na; Guo, Yu-Qing; Zhang, Bin; Chen, Hu

    2014-02-01

    This study was aimed to investigate the distribution of compact bone mesenchymal stem cells(MSC) marked with lentiviral plasmid pGC FU-RFP-LV in lung tissue and bone marrow of mouse. The MSC were infected by lentivirus with infection efficiency 78%, the infected MSC were injected into BALB/c mice via tail veins in concentration of 1×10(6) /mouse. The mice were randomly divided into 4 group according to 4 time points as 1, 2, 5 and 7 days. The lung tissue and bone marrow were taken and made of frozen sections and smears respectively in order to observed the distributions of MSC. The results indicated that the lentiviral infected MSC displayed phenotypes and biological characteristics which conformed to MSC by immunophenotyping analysis and induction differentiation detection. After the MSC were infected with optimal viral titer MOI = 50, the cell growth no significantly changed; the fluorescent microscopy revealed that the distributions of MSC in bone marrow on day 1, 2, 5 and 7 were 0.50 ± 0.20, 0.67 ± 0.23, 0.53 ± 0.14, 0.33 ± 0.16; those in lung tissue were 0.55 ± 0.15, 0.47 ± 0.13, 0.29 ± 0.13, 0.26 ± 0.08. It is concluded that the distribution of MSC in lung tissue reaches a peak on day 1, while distribution of MSC in bone marrow reaches a peak on day 2. The distribution of mouse MSC relates with RFP gene expression and implantation of MSC in lung tissue and bone marrow.

  6. Reconstruction of irradiated bone segmental defects with a biomaterial associating MBCP+(R), microstructured collagen membrane and total bone marrow grafting: an experimental study in rabbits.

    PubMed

    Jégoux, Franck; Goyenvalle, Eric; Cognet, Ronan; Malard, Olivier; Moreau, Francoise; Daculsi, Guy; Aguado, Eric

    2009-12-15

    The bone tissue engineering models used today are still a long way from any oncologic application as immediate postimplantation irradiation would decrease their osteoinductive potential. The aim of this study was to reconstruct a segmental critical size defect in a weight-bearing bone irradiated after implantation. Six white New Zealand rabbits were immediately implanted with a biomaterial associating resorbable collagen membrane EZ(R) filled and micro-macroporous biphasic calcium phosphate granules (MBCP+(R)). After a daily schedule of radiation delivery, and within 4 weeks, a total autologous bone marrow (BM) graft was injected percutaneously into the center of the implant. All the animals were sacrificed at 16 weeks. Successful osseous colonization was found to have bridged the entire length of the defects. Identical distribution of bone ingrowth and residual ceramics at the different levels of the implant suggests that the BM graft plays an osteoinductive role in the center of the defect. Periosteum-like formation was observed at the periphery, with the collagen membrane most likely playing a role. This model succeeded in bridging a large segmental defect in weight-bearing bone with immediate postimplantation fractionated radiation delivery. This has significant implications for the bone tissue engineering approach to patients with cancer-related bone defects.

  7. Stromal cell-derived factor-1 mediates changes of bone marrow stem cells during the bone repair process.

    PubMed

    Okada, Kiyotaka; Kawao, Naoyuki; Yano, Masato; Tamura, Yukinori; Kurashimo, Shinzi; Okumoto, Katsumi; Kojima, Kotarou; Kaji, Hiroshi

    2016-01-01

    Osteoblasts, osteoclasts, chondrocytes, and macrophages that participate in the bone repair process are derived from hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). However, the roles of these stem cells during the repair of injured bone tissue are still unclear. In the present study, we examined the effects of bone defect on HSCs and MSCs in bone marrow and spleen in 75 mice and its mechanism. We analyzed the HSC and MSC populations in these tissues of a mouse with femoral bone damage by using flow cytometry. The number of HSCs in the bone marrow of mice with damaged femurs was significantly lower than the number of these cells in the bone marrow of the contralateral intact femurs on day 2 after injury. Meanwhile, the number of MSCs in the bone marrow of mice with damaged femurs was significantly higher than that of the contralateral femurs. Both intraperitoneal administration of AMD3100, a C-X-C chemokine receptor 4 (CXCR4) antagonist, and local treatment with an anti-stromal cell-derived factor-1 (SDF-1) antibody blunted the observed decrease in HSC and increase in MSC populations within the bone marrow of injured femurs. In conclusion, the present study revealed that there is a concurrent decrease and increase in the numbers of HSCs and MSCs, respectively, in the bone marrow during repair of mouse femoral bone damage. Furthermore, the SDF-1/CXCR4 system was implicated as contributing to the changes in these stem cell populations upon bone injury.

  8. The effect of erythropoietin on autologous stem cell-mediated bone regeneration.

    PubMed

    Nair, Ashwin M; Tsai, Yi-Ting; Shah, Krishna M; Shen, Jinhui; Weng, Hong; Zhou, Jun; Sun, Xiankai; Saxena, Ramesh; Borrelli, Joseph; Tang, Liping

    2013-10-01

    Mesenchymal stem cells (MSCs) although used for bone tissue engineering are limited by the requirement of isolation and culture prior to transplantation. Our recent studies have shown that biomaterial implants can be engineered to facilitate the recruitment of MSCs. In this study, we explore the ability of these implants to direct the recruitment and the differentiation of MSCs in the setting of a bone defect. We initially determined that both stromal derived factor-1alpha (SDF-1α) and erythropoietin (Epo) prompted different degrees of MSC recruitment. Additionally, we found that Epo and bone morphogenetic protein-2 (BMP-2), but not SDF-1α, triggered the osteogenic differentiation of MSCs in vitro. We then investigated the possibility of directing autologous MSC-mediated bone regeneration using a murine calvaria model. Consistent with our in vitro observations, Epo-releasing scaffolds were found to be more potent in bridging the defect than BMP-2 loaded scaffolds, as determined by computed tomography (CT) scanning, fluorescent imaging and histological analyses. These results demonstrate the tremendous potential, directing the recruitment and differentiation of autologous MSCs has in the field of tissue regeneration.

  9. Multiorgan WU Polyomavirus Infection in Bone Marrow Transplant Recipient

    PubMed Central

    Siebrasse, Erica A.; Nguyen, Nang L.; Willby, Melisa J.; Erdman, Dean D.; Menegus, Marilyn A.

    2016-01-01

    WU polyomavirus (WUPyV) was detected in a bone marrow transplant recipient with severe acute respiratory distress syndrome who died in 2001. Crystalline lattices of polyomavirus-like particles were observed in the patient’s lung by electron microscopy. WUPyV was detected in the lung and other tissues by real-time quantitative PCR and identified in the lung and trachea by immunohistochemistry. A subset of WUPyV-positive cells in the lung had morphologic features of macrophages. Although the role of WUPyV as a human pathogen remains unclear, these results clearly demonstrate evidence for infection of respiratory tract tissues in this patient. PMID:26691850

  10. Mouse bone marrow cytogenetic damage produced by residues of tequila.

    PubMed

    Madrigal-Bujaidar, E; Rojas, A; Ramos, A; Rosas, E; Díaz Barriga-Arceo, S

    1990-06-01

    Five concentrations (50-860 mg/kg) of residues obtained after distillation and lyophilization of commercial tequila were injected into mice for evaluation of chromosome aberrations, sister-chromatid exchanges, and proliferation kinetics in mouse bone marrow cells. Appropriate positive and negative controls were included. Our results showed significant dose-related increases of chromosomal aberrations starting at 50 mg/kg and for sister-chromatid exchanges at 430 mg/kg. Cellular proliferation kinetics showed no alterations. With these data we demonstrated that the residues of tequila are genotoxic in vivo.

  11. Bone marrow mononuclears from murine tibia after spaceflight on biosatellite

    NASA Astrophysics Data System (ADS)

    Andreeva, Elena; Roe, Maria; Buravkova, Ludmila; Andrianova, Irina; Goncharova, Elena; Gornostaeva, Alexandra

    Elucidation of the space flight effects on the adult stem and progenitor cells is an important goal in space biology and medicine. A unique opportunity for this is provided by project "BION -M1". The purpose of this study was to evaluate the effects of a 30-day flight on biosatellite "BION - M1" and the subsequent 7-day recovery on the quantity, viability, immunophenotype of mononuclears from murine tibia bone marrow. Also the in vitro characterization of functional capacity of multipotent mesenchymal stromal cells (MSCs) was scheduled. Under the project, the S57black/6 mice were divided into groups: spaceflight/vivarium control, recovery after spaceflight/ vivarium control to recovery. Bone marrow mononuclears were isolated from the tibia and immunophenotyped using antibodies against CD45, CD34, CD90 on a flow cytometer Epics XL (Beckman Coulter). A part of the each pool was frozen for subsequent estimation of hematopoietic colony-forming units (CFU), the rest was used for the evaluation of fibroblast CFU (CFUf) number, MSC proliferative activity and osteogenic potency. The cell number in the flight group was significantly lower than in the vivarium control group. There were no differences in this parameter between flight and control groups after 7 days of recovery. The mononuclears viability was more than 95 percent in all examined groups. Flow cytometric analysis showed no differences in the bone marrow cell immunophenotype (CD45, CD34, CD90.1 (Thy1)), but the flight animals had more large-sized CD45+mononuclears, than the control groups of mice. There was no difference in the CFUf number between groups. After 7 days in vitro the MSC number in flight group was twice higher than in vivarium group, after 10 days - 4 times higher. These data may indicate a higher proliferative activity of MSCs after spaceflight. MSCs showed the same and high alkaline phosphatase activity, both in flight and in the control groups, suggesting no effect of spaceflight factors on early

  12. Ehrlichiosis: a cause of bone marrow hypoplasia in humans.

    PubMed

    Pearce, C J; Conrad, M E; Nolan, P E; Fishbein, D B; Dawson, J E

    1988-05-01

    Infection with Ehrlichia canis should be suspected in patients with fever, headache, malaise, leukopenia, thrombocytopenia, and a history of recent exposure to ticks. The cytopenia is caused by bone marrow hypoplasia which may be severe. The disease may be confused with spotless Rocky Mountain spotted fever but can be differentiated from this infection serologically with acute and convalescent sea. In humans, recovery has occurred with and without antibiotic therapy. However, prompt antibiotic therapy is advised prior to serologic studies, especially in immunocompromised individuals, splenectomized persons, and patients with AIDS-who may develop a more overwhelming rickettsial infection.

  13. Tuberculosis in pediatric oncology and bone marrow transplantation patients.

    PubMed

    Cruz, Andrea T; Airewele, Gladstone; Starke, Jeffrey R

    2014-08-01

    Five children with malignancies (3 hematologic, 1 medulloblastoma, 1 hepatoblastoma) and one bone marrow transplant patient were treated for tuberculosis over a 30-year period. Three had pulmonary disease, 3 disseminated tuberculosis, and 1 had scrofula. Four of five had positive tuberculin skin tests, cultures were positive in 5/6 children. One child died of disseminated TB after engraftment, and one child had hepatotoxicity likely related to tuberculosis therapy. All cases were potentially preventable had they been screened due to established risk factors of foreign birth (4/6) or parental foreign birth (2/6). All children should be screened for latent tuberculosis before chemotherapy.

  14. Multiorgan WU Polyomavirus Infection in Bone Marrow Transplant Recipient.

    PubMed

    Siebrasse, Erica A; Nguyen, Nang L; Willby, Melisa J; Erdman, Dean D; Menegus, Marilyn A; Wang, David

    2016-01-01

    WU polyomavirus (WUPyV) was detected in a bone marrow transplant recipient with severe acute respiratory distress syndrome who died in 2001. Crystalline lattices of polyomavirus-like particles were observed in the patient's lung by electron microscopy. WUPyV was detected in the lung and other tissues by real-time quantitative PCR and identified in the lung and trachea by immunohistochemistry. A subset of WUPyV-positive cells in the lung had morphologic features of macrophages. Although the role of WUPyV as a human pathogen remains unclear, these results clearly demonstrate evidence for infection of respiratory tract tissues in this patient.

  15. Mouse Models in Bone Marrow Transplantation and Adoptive Cellular Therapy

    PubMed Central

    Arber, Caroline; Brenner, Malcolm K.; Reddy, Pavan

    2014-01-01

    Mouse models of transplantation have been indispensable to the development of bone marrow transplantation (BMT). Their role in the generation of basic science knowledge is invaluable and is subject to discussion below. However, this article focuses on the direct role and relevance of mouse models towards the clinical development and advances in BMT and adoptive T-cell therapy for human diseases. The authors aim to present a thoughtful perspective on the pros and cons of mouse models while noting that despite imperfections these models are obligatory for the development of science-based medicine. PMID:24216170

  16. Repair of goat tibial defects with bone marrow stromal cells and beta-tricalcium phosphate.

    PubMed

    Liu, Guangpeng; Zhao, Li; Zhang, Wenjie; Cui, Lei; Liu, Wei; Cao, Yilin

    2008-06-01

    Tissue engineering techniques have been proven effective in bone regeneration and repairing load-bearing bone defects. Previous studies, however, have heretofore been limited to the use of slowdegradable or natural biomaterials as scaffolds. There are, however, no reports on using biodegradable, synthetic beta-tricalcium phosphate (beta-TCP) as scaffolds to repair weight-bearing bone defects in large animals. In the present study, highly porous beta-TCP scaffolds prepared by the polymeric sponge method were used to repair goat tibial defects. Fifteen goats were randomly assigned to one of three groups, and a 26 mm-long defect at the middle part of the right tibia in each goat was created. In Group A (six goats), a porous beta-TCP ceramic cylinder that had been loaded with osteogenically induced autologous bone marrow stromal cells (BMSCs) was implanted in the defect of each animal. In Group B (six goats), the same beta-TCP ceramic cylinder without any cells loaded was placed in the defect. In Group C (three goats), the defect was left untreated. In Group A, bony union can be observed by gross view, X-ray and micro-computed tomography (Micro-CT) detection, and histological observation at 32 weeks post-implantation. The implanted beta-TCP scaffolds were almost completely replaced by tissue-engineered bone. Bone mineral density in the repaired area of Group A was significantly higher (p < 0.05) than that of Group B, in which scant new bone was formed in each defect and the beta-TCP hadn't been completely resorbed at 32 weeks. Moreover, the tissue-engineered bone of Group A had similar biomechanical properties as that of the normal left tibia in terms of bending strength and Young's modulus (p > 0.05). In Group C, little or no new bone was formed, and non-union occurred, showing that the 26 mm segmental defect of the goat tibia was critical sized at 32 weeks. Thus, it can be concluded that the mechanical properties of the BMSCs/beta-TCP composites could be much

  17. Inhibition of PPARgamma prevents type I diabetic bone marrow adiposity but not bone loss.

    PubMed

    Botolin, Sergiu; McCabe, Laura R

    2006-12-01

    Diabetes type I is associated with bone loss and increased bone adiposity. Osteoblasts and adipocytes are both derived from mesenchymal stem cells located in the bone marrow, therefore we hypothesized that if we could block adipocyte differentiation we might prevent bone loss in diabetic mice. Control and insulin-deficient diabetic BALB/c mice were chronically treated with a peroxisomal proliferator-activated receptor gamma (PPARgamma) antagonist, bisphenol-A-diglycidyl ether (BADGE), to block adipocyte differentiation. Effects on bone density, adiposity, and gene expression were measured. BADGE treatment did not prevent diabetes-associated hyperglycemia or weight loss, but did prevent diabetes-induced hyperlipidemia and effectively blocked diabetes type I-induced bone adiposity. Despite this, BADGE treatment did not prevent diabetes type I suppression of osteoblast markers (runx2 and osteocalcin) and bone loss (as determined by micro-computed tomography). BADGE did not suppress osteoblast gene expression or bone mineral density in control mice, however, chronic (but not acute) BADGE treatment did suppress osteocalcin expression in osteoblasts in vitro. Taken together, our findings suggest that BADGE treatment is an effective approach to reduce serum triglyceride and free fatty acid levels as well as bone adiposity associated with type I diabetes. The inability of BADGE treatment to prevent bone loss in diabetic mice suggests that marrow adiposity is not linked to bone density status in type I diabetes, but we cannot exclude the possibility of additional BADGE effects on osteoblasts or other bone cells, which could contribute to preventing the rescue of the bone phenotype.

  18. Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow-derived stem cells in the treatment of Leber's hereditary optic neuropathy

    PubMed Central

    Weiss, Jeffrey N.; Levy, Steven; Benes, Susan C.

    2016-01-01

    The Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthalmology trial registered at ClinicalTrials.gov (identifier: NCT01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber's hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study (ETDRS) of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autologous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber's hereditary optic neuropathy may be a viable treatment option. PMID:27904503

  19. Use of autologous bone graft in anterior cervical decompression: morbidity & quality of life analysis

    PubMed Central

    2009-01-01

    Background Autologous iliac crest graft has long been the gold standard graft material used in cervical fusion. However its harvest has significant associated morbidity, including protracted postoperative pain scores at the harvest site. Thus its continued practice warrants scrutiny, particularly now that alternatives are available. Our aims were to assess incidence and nature of complications associated with iliac crest harvest when performed in the setting of Anterior Cervical Decompression (ACD). Also, to perform a comparative analysis of patient satisfaction and quality of life scores after ACD surgeries, when performed with and without iliac graft harvest. Methods All patients who underwent consecutive ACD procedures, with and without the use of autologous iliac crest graft, over a 48 month period were included (n = 53). Patients were assessed clinically at a minimum of 12 months postoperatively and administered 2 validated quality of life questionnaires: the SF-36 and Cervical Spine Outcomes Questionnaires (Response rate 96%). Primary composite endpoints included incidence of bone graft donor site morbidity, pain scores, operative duration, and quality of life scores. Results Patients who underwent iliac graft harvest experienced significant peri-operative donor site specific morbidity, including a high incidence of pain at the iliac crest (90%), iliac wound infection (7%), a jejunal perforation, and longer operative duration (285 minutes vs. 238 minutes, p = 0.026). Longer term follow-up demonstrated protracted postoperative pain at the harvest site and significantly lower mental health scores on both quality of life instruments, for those patients who underwent autologous graft harvest Conclusion ACD with iliac crest graft harvest is associated with significant iliac crest donor site morbidity and lower quality of life at greater than 12 months post operatively. This is now avoidable by using alternatives to autologous bone without compromising clinical or

  20. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a... intralaboratory variation with the in vivo bone morrow metaphase procedure,” Handbook of mutagenicity...

  1. CHANGES IN OUTLYING BONE MARROW ACCOMPANYING A LOCAL INCREASE OF TEMPERATURE WITHIN PHYSIOLOGICAL LIMITS

    PubMed Central

    Huggins, Charles; Blocksom, B. H.

    1936-01-01

    A great difference exists in the adult bone marrow of central bones as compared with outlying bones of the mammalia and avia, the distal bones being at a great disadvantage from the standpoint of blood cell production. Several experimental procedures are reported by which this disadvantage is overcome and in consequence fatty marrow of outlying bones is replaced by red marrow occurring chiefly at the epiphyseal regions, unless a low oxygen stimulus is also provided when marrow of the diaphysis becomes involved. A common factor in all of the experiments was an elevation of temperature beyond that prevailing in these distal regions, and it is felt that the evidence warrants the opinion that the cause of improvement is thermal. In some experiments, blood cell formation was increasing while the heat was adversely affecting the testis. The experiments permit construction of a general theory of fat distribution in bone marrow. In certain grafts of precartilage to other rats, normal differentiation into bone, cartilage, and marrow occurred, while in others cartilage and very small amounts of primitive marrow developed with slight, or no bone formation. Cartilage was always successfully engrafted. The capacity to form sinusoids in bone marrow is determined by the nature of the tissue rather than by the ingrowing endothelium. PMID:19870534

  2. Computational modelling of the mechanics of trabecular bone and marrow using fluid structure interaction techniques.

    PubMed

    Birmingham, E; Grogan, J A; Niebur, G L; McNamara, L M; McHugh, P E

    2013-04-01

    Bone marrow found within the porous structure of trabecular bone provides a specialized environment for numerous cell types, including mesenchymal stem cells (MSCs). Studies have sought to characterize the mechanical environment imposed on MSCs, however, a particular challenge is that marrow displays the characteristics of a fluid, while surrounded by bone that is subject to deformation, and previous experimental and computational studies have been unable to fully capture the resulting complex mechanical environment. The objective of this study was to develop a fluid structure interaction (FSI) model of trabecular bone and marrow to predict the mechanical environment of MSCs in vivo and to examine how this environment changes during osteoporosis. An idealized repeating unit was used to compare FSI techniques to a computational fluid dynamics only approach. These techniques were used to determine the effect of lower bone mass and different marrow viscosities, representative of osteoporosis, on the shear stress generated within bone marrow. Results report that shear stresses generated within bone marrow under physiological loading conditions are within the range known to stimulate a mechanobiological response in MSCs in vitro. Additionally, lower bone mass leads to an increase in the shear stress generated within the marrow, while a decrease in bone marrow viscosity reduces this generated shear stress.

  3. Extensive bone marrow necrosis associated with antiphospholipid antibodies.

    PubMed

    Bulvik, S; Aronson, I; Ress, S; Jacobs, P

    1995-06-01

    Bone marrow necrosis (BMN), defined morphologically by destruction of hematopoietic tissue, including the stroma, with preservation of the bone, is a rare syndrome. The conditions in which it is seen include sickle cell disease, acute leukemia, metastatic neoplasia, and bacterial infection, particularly when hypovolemia and septic shock are present. BMN is also associated with disseminated intravascular coagulation (DIC) following irradiation and antineoplastic therapy. The antiphospolipid syndrome (APS) is characterized by antibodies directed against the antiphospolipid substrate. Because this substrate is prominently involved in the coagulation cascade and widely distributed on cell walls, patients present with venous or arterial thromboses, recurrent abortion, thrombocytopenia, and Coombs' positive hemolytic anemia, typically with raised anticardiolipin antibodies or a diagnostic lupus anticoagulant test. BMN does not appear to have been previously recognized in this context. We report what we believe to be the first such case and suggest that the high titers of antibodies present may have played a central role in its pathogenesis.

  4. Cutaneous mast cell maturation does not depend on an intact bone marrow microenvironment

    SciTech Connect

    Charley, M.R.; Mikhael, A.; Sontheimer, R.D.; Gilliam, J.N.; Bennett, M.

    1984-01-01

    A study was made to determine whether the maturation of murine cutaneous mast cells from stem cells depends on an intact bone marrow microenvironment. Normal bone marrow cells (+/+) were infused into 2 groups of mast cell-deficient mice: WBB6F1-W/Wv mice and /sup 89/Sr-pretreated W/Wv mice. /sup 89/Sr is a long-lived bone-seeking radioisotope which provides continuous irradiation of the marrow and thereby ablates the marrow microenvironment. Skin biopsies revealed that the /sup 89/Sr-pretreated mice and the controls had repopulated their skin with mast cells equally well. Natural killer cell function was significantly depressed in the /sup 89/Sr-treated mice, confirming that the marrow microenvironment had been functionally altered. It appears that, although the precursors for cutaneous mast cells are marrow derived, they do not need an intact marrow microenvironment for maturation.

  5. Granulomatous bone marrow disease. A review of the literature and clinicopathologic analysis of 58 cases.

    PubMed

    Bodem, C R; Hamory, B H; Taylor, H M; Kleopfer, L

    1983-11-01

    We have reviewed 58 cases of bone marrow granuloma at a single institution over a 20-year time span, and have summarized the available English literature. We conclude that bone marrow granulomas are an infrequent pathologic finding which, when found, require definition as to an underlying etiology. Undoubtedly, the illnesses associated with marrow granuloma are similar to those causing granulomatous hepatitis. The following additional statements may justifiably be made based on this review. There are no morphologic features which allow reliable differentiation between the causes of bone marrow granuloma. By combining careful histologic, microbiologic, and serologic techniques, an etiology can be documented in most (87%) patients with marrow granulomas. A medication history is an important element of this evaluation. Rocky Mountain spotted fever, cytomegalovirus infection, ibuprofen, acute lymphocytic leukemia, and various collagen vascular diseases should be added to the list of causes of marrow granuloma. The prognostic significance of marrow granuloma in patients without an ascertainable underlying illness remains unclear.

  6. Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration

    PubMed Central

    Vega-Najera, Carlos; Leal-Contreras, Carlos; Leal-Berumen, Irene

    2013-01-01

    The compartment syndrome is a condition characterized by a raised hydraulic pressure within a closed and non expandable anatomical space. It leads to a vascular insufficiency that becomes critical once the vascular flow cannot return the fluids back to the venous system. This causes a potential irreversible damage of the contents of the compartment, especially within the muscle tissues. Gluteal compartment syndrome (GCS) secondary to hematomas is seldom reported. Here we present a case of a 51-year-old patient with history of a non-Hodgkin lymphoma who underwent a bone marrow aspiration from the posterior iliac crest that had excessive bleeding at the puncture zone. The patient complained of increasing pain, tenderness, and buttock swelling. Intraoperative pressure validation of the gluteal compartment was performed, and a GCS was diagnosed. The patient was treated with a gluteal region fasciotomy. The patient recovered from pain and swelling and was discharged shortly after from the hospital. We believe clotting and hematologic disorders are a primary risk factor in patients who require bone marrow aspirations or biopsies. It is important to improve awareness of GCS in order to achieve early diagnosis, avoid complications, and have a better prognosis. PMID:24392235

  7. Coping patterns among bone marrow transplant patients: a hermeneutical inquiry.

    PubMed

    Shuster, G F; Steeves, R H; Onega, L; Richardson, B

    1996-08-01

    Bone marrow transplantation (BMT) has recently become the treatment of choice for a number of malignancies. This procedure is highly technical, involving the use of radiation and chemotherapy to destroy the patient's diseased bone marrow and with it functions of the entire immune system. It is a process with toxic effects that are experienced by all patients to varying degrees. A great deal of research related to the physiological aspects of this procedure has already been done, but considerably fewer studies have examined the psychosocial aspects of the BMT procedure from the patient's perspective. Knowledge about how BMT patients understand this process and cope with its effects is important information for nurses taking care of these patients. The purpose of the study was to describe in depth the patterns of meaning employed by patients in the hospital as they coped with the experience of their BMT. Eleven patients were interviewed from one to four times a week throughout their hospitalization. Hermeneutic analysis was used to identify five major themes: physiological functioning, alertness, attitude, social relationships, and spirituality. Implications from the findings for nursing practice are discussed.

  8. Prevention of diabetes in rats by bone marrow transplantation.

    PubMed

    Alinaji; Silvers, W K; Bellgrau, D; Anderson, A O; Plotkin, S; Barker, C F

    1981-09-01

    Hyperglycemia, hypoinsulinemia and ketonemia often develop abruptly in previously normal young "BB" rats. The syndrome mimics human juvenile diabetes closely and is, thus, appropriate for assessing pancreatic transplantation. Transplantation of islet cells from closely histocompatible Wistar Furth (WF) donor resulted in permanent normoglycemia when immunosuppression with ALS was given. However, when islet cells from nondiabetic "BB" donors were transplanted to nonimmunosuppressed diabetic "BB" recipients, only transient normoglycemia followed. Transplantation of WF islets cells also failed in diabetic "BB" rats which were tolerant of WF antigens, again suggesting destruction of transplanted islet cells by the original disease process-possibly autoimmunity. Evidence for autoimmunity was strengthened by the finding that newly diabetic "BB" rats could be rendered normoglycemic by immunosuppression. Since genetic susceptibility to spontaneous autoimmune diabetes is unique to some members of the "BB" stock, an attempt was made to alter their vulnerability by modifying their cellular immune system. Accordingly, 50 million bone marrow cells from WF donors were inoculated into half the newborn members of "BB" litters, leaving the littermates as unmodified controls. Most bone marrow recipients were protected, only four of 37 (10.8%) ever becoming diabetic, while the incidence of diabetes in noninoculated littermates was 22 of 39 (56.4%). The ultimate goal in human diabetes, which also seems very likely to be an autoimmune disease, may not be replacement of destroyed islet cells but identification of potentially susceptible children and prevention of islet destruction by immunologic manipulation.

  9. Anemia of immobility: caused by adipocyte accumulation in bone marrow.

    PubMed

    Payne, Michael W C; Uhthoff, Hans K; Trudel, Guy

    2007-01-01

    Anemia of chronic disease has long been used to classify a non-regenerative, low-grade, chronic, normocytic, normochromic anemia that presents with no obvious etiology. Within this group, some patients have a chronic inflammatory condition that limits erythrocyte generation or access to iron stores. This specific type of anemia has been termed anemia of chronic inflammation. However, a substantial remainder of patients diagnosed with anemia of chronic disease present with no active inflammation. These include many clinical populations with reduced limb loading, such as spinal cord injured patients, astronauts, elderly people with limited mobility and experimental bed-rest subjects. In some populations with decreased mobility, accumulation of fat in the bone marrow has been demonstrated. We hypothesize that adipocyte accumulation in bone marrow both passively and actively impairs erythropoiesis and thus defines a new type of anemia called anemia of immobility. The non-specific umbrella term anemia of chronic disease thus becomes obsolete in favour of either the diagnosis of anemia of immobility or anemia of chronic inflammation according to the distinct mechanism involved.

  10. ICSH guidelines for the standardization of bone marrow immunohistochemistry.

    PubMed

    Torlakovic, E E; Brynes, R K; Hyjek, E; Lee, S-H; Kreipe, H; Kremer, M; McKenna, R; Sadahira, Y; Tzankov, A; Reis, M; Porwit, A

    2015-08-01

    Bone marrow (BM) tissue biopsy evaluation, including trephine biopsy and clot section, is an integral part of BM investigation and is often followed by ancillary studies, in particular immunohistochemistry (IHC). IHC provides in situ coupling of morphological assessment and immunophenotype. The number of different IHC tests that can be applied to BM trephine biopsies and the number of indications for IHC testing is increasing concurrently with the development of flow cytometry and molecular diagnostic methods. An international Working Party for the Standardization of Bone Marrow IHC was formed by the International Council for Standardization in Hematology (ICSH) to prepare a set of guidelines for the standardization of BM IHC based on currently available published evidence and modern understanding of quality assurance principles as applied to IHC in general. The guidelines were discussed at the ICSH General Assemblies and reviewed by an international panel of experts to achieve further consensus and represent further development of the previously published ICSH guidelines for the standardization of BM specimens handling and reports.

  11. The effects of simulated hypogravity on murine bone marrow cells

    NASA Technical Reports Server (NTRS)

    Lawless, Desales

    1989-01-01

    Mouse bone marrow cells grown in complete medium at unit gravity were compared with a similar population cultured in conditions that mimic some aspects of microgravity. After the cells adjusted to the conditions that simulated microgravity, they proliferated as fetal or oncogenic populations; their numbers doubled in twelve hour periods. Differentiated subpopulations were depleted from the heterogeneous mixture with time and the undifferentiated hematopoietic stem cells increased in numbers. The cells in the control groups in unit gravity and those in the bioreactors in conditions of microgravity were monitored under a number of parameters. Each were phenotyped as to cell surface antigens using a panel of monoclonal antibodies and flow cytometry. Other parameters compared included: pH, glucose uptake, oxygen consumption and carbon-dioxide production. Nuclear DNA was monitored by flow cytometry. Functional responses were studied by mitogenic stimulation by various lectins. The importance of these findings should have relevance to the space program. Cells should behave predictably in zero gravity; specific populations can be eliminated from diverse populations and other populations isolated. The availability of stem cell populations will enhance both bone marrow and gene transplant programs. Stem cells will permit developmental biologists study the paths of hematopoiesis.

  12. Registered bone marrow donors' views on bodily donations.

    PubMed

    Sanner, M A

    1997-01-01

    The attitudes of 463 potential bone marrow donors toward blood donation, kidney donation in life, organ donation after death, autopsy, and donation of the whole body for anatomic dissection were surveyed, using a questionnaire that had previously been employed for assessing the attitudes of the public. The response rate was 96%. Three quarters of the respondents were blood donors and recruited via the blood center. The proportion that accepted the procedures varied between 24% for anatomic dissection and 97% for autopsy. Differences were small between individuals with positive attitudes and individuals who had also actively taken steps to activate these attitudes. Compared with the public, the bone marrow donors were more positive to all kinds of bodily donations. The conclusion is that if one is prepared to give from the body in life, one is also prepared to give after death. The results may indicate less death anxiety and fear of physical injury, and less fear of chaos either with or without altruism compared to the public.

  13. Bone Marrow Gene Therapy for HIV/AIDS

    PubMed Central

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-01-01

    Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV). This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs) with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described. PMID:26193303

  14. Bone Marrow Gene Therapy for HIV/AIDS.

    PubMed

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-07-17

    Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV). This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs) with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described.

  15. Adipose lineage specification of bone marrow-derived myeloid cells

    PubMed Central

    Majka, Susan M.; Miller, Heidi L.; Sullivan, Timothy; Erickson, Paul F.; Kong, Raymond; Weiser-Evans, Mary; Nemenoff, Raphael; Moldovan, Radu; Morandi, Shelley A.; Davis, James A.; Klemm, Dwight J.

    2012-01-01

    We have reported the production of white adipocytes in adipose tissue from hematopoietic progenitors arising from bone marrow. However, technical challenges have hindered detection of this adipocyte population by certain other laboratories. These disparate results highlight the need for sensitive and definitive techniques to identify bone marrow progenitor (BMP)-derived adipocytes. In these studies we exploited new models and methods to enhance detection of this adipocyte population. Here we showed that confocal microscopy with spectrum acquisition could effectively identify green fluorescent protein (GFP) positive BMP-derived adipocytes by matching their fluorescence spectrum to that of native GFP. Likewise, imaging flow cytometry made it possible to visualize intact unilocular and multilocular GFP-positive BMP-derived adipocytes and distinguished them from non-fluorescent adipocytes and cell debris in the cytometer flow stream. We also devised a strategy to detect marker genes in flow-enriched adipocytes from which stromal cells were excluded. This technique also proved to be an efficient means for detecting genetically labeled adipocytes and should be applicable to models in which marker gene expression is low or absent. Finally, in vivo imaging of mice transplanted with BM from adipocyte-targeted luciferase donors showed a time-dependent increase in luciferase activity, with the bulk of luciferase activity confined to adipocytes rather than stromal cells. These results confirmed and extended our previous reports and provided proof-of-principle for sensitive techniques and models for detection and study of these unique cells. PMID:23700536

  16. Busulfan and total body irradiation as antihematopoietic stem cell agents in the preparation of patients with congenital bone marrow disorders for allogenic bone marrow transplantation

    SciTech Connect

    Parkman, R.; Rappeport, J.M.; Hellman, S.; Lipton, J.; Smith, B.; Geha, R.; Nathan, D.G.

    1984-10-01

    The capacity of busulfan and total body irradiation to ablate hematopoietic stem cells as preparation for the allogeneic bone marrow transplantation of patients with congenital bone marrow disorders was studied. Fourteen patients received 18 transplants; busulfan was used in the preparatory regimen of eight transplants and total body irradiation in the regimens of six transplants. Sustained hematopoietic ablation was achieved in six of eight patients prepared with busulfan and in all six patients prepared with total body irradiation. Three patients prepared with total body irradiation died with idiopathic interstitial pneumonitis, whereas no patients receiving busulfan developed interstitial pneumonitis. The optimal antihematopoietic stem cell agent to be used for the preparation of patients with congenital bone marrow disorder for bone marrow transplantation is not certain.

  17. Roles of bone marrow cells in skeletal metastases: no longer bystanders.

    PubMed

    Park, Serk In; Soki, Fabiana N; McCauley, Laurie K

    2011-12-01

    Bone serves one of the most congenial metastatic microenvironments for multiple types of solid tumors, but its role in this process remains under-explored. Among many cell populations constituting the bone and bone marrow microenvironment, osteoblasts (originated from mesenchymal stem cells) and osteoclasts (originated from hematopoietic stem cells) have been the main research focus for pro-tumorigenic roles. Recently, increasing evidence further elucidates that hematopoietic lineage cells as well as stromal cells in the bone marrow mediate distinct but critical functions in tumor growth, metastasis, angiogenesis and apoptosis in the bone microenvironment. This review article summarizes the key evidence describing differential roles of bone marrow cells, including hematopoietic stem cells (HSCs), megakaryocytes, macrophages and myeloid-derived suppressor cells in the development of metastatic bone lesions. HSCs promote tumor growth by switching on angiogenesis, but at the same time compete with metastatic tumor cells for occupancy of osteoblastic niche. Megakaryocytes negatively regulate the extravasating tumor cells by inducing apoptosis and suppressing proliferation. Macrophages and myeloid cells have pro-tumorigenic roles in general, suggesting a similar effect in the bone marrow. Hematopoietic and stromal cell populations in the bone marrow, previously considered as simple by-standers in the context of tumor metastasis, have distinct and active roles in promoting or suppressing tumor growth and metastasis in bone. Further investigation on the extended roles of bone marrow cells will help formulate better approaches to treatment through improved understanding of the metastatic bone microenvironment.

  18. Functional characterisation of bone marrow-derived mesenchymal stromal cells from COPD patients

    PubMed Central

    Roelofs, Helene; Zarcone, Maria C.; Taube, Christian; Stolk, Jan; Hiemstra, Pieter S.

    2016-01-01

    Autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) are evaluated for clinical use in chronic obstructive pulmonary disease (COPD) patients, but it is unclear whether COPD affects BM-MSCs. To investigate this, BM-MSCs from nine COPD patients and nine non-COPD age-matched controls were compared with regard to immunophenotype, growth and differentiation potential, and migration capacity. Other functional assays included the response to pro-inflammatory stimuli and inducers of the nuclear factor (erythroid derived 2)-like 2 antioxidant response element (Nrf2-ARE) pathway, and effects on NCI-H292 airway epithelial cells. No significant differences were observed in terms of morphology, proliferation and migration, except for increased adipocyte differentiation potential in the COPD group. Both groups were comparable regarding mRNA expression of growth factors and inflammatory mediators, and in their potential to induce mRNA expression of epidermal growth factor receptor ligands in NCI-H292 airway epithelial cells. MSCs from COPD patients secreted more interleukin-6 in response to pro-inflammatory stimuli. Activation of the Nrf2-ARE pathway resulted in a comparable induction of mRNA expression of four target genes, but the expression of the NAD(P)H:quinone oxidoreductase 1 gene NQO1 was lower in MSCs from COPD patients. The observation that MSCs from COPD patients are phenotypically and functionally comparable to those from non-COPD controls implies that autologous MSCs can be considered for use in the setting of clinical trials as a treatment for COPD. PMID:27730190

  19. Bone marrow examination for identifying malaria in fever of unknown origin.

    PubMed

    Mirdha, B R; Samantray, J C; Mishra, B; Xess, I

    1999-02-01

    To determine the utility of bone marrow examination for the diagnosis of malaria in patients with persistent fever for prolonged duration, we prospectively studied individuals undergoing diagnostic bone marrow examinations between January 1992 to December 1996. All marrow examinations of patients were examined microbiologically and resulted in diagnosis of malaria in 6.6% of the total patients studied. No case of bacterial, mycobacterial or fungal infection was diagnosed. The diagnostic efficacy of bone marrow for evidence of malaria was very useful in febrile individuals for whom the diagnosis was otherwise unknown.

  20. Electrostimulation and morphologic study of the nerves to the bone marrow of the albino rat.

    PubMed

    DePace, D M; Webber, R H

    1975-01-01

    The innervation of the bone marrow of the albino rat was investigated by electrostimulation and morphological methods. Stimulation of the lumbar sympathetic trunks resulted in the release of reticulocytes and neutrophils into the circulating blood. The effects of stimulation on other cell types in the bone marrow could not be definitely established. It was concluded that the nerve fibers to the bone marrow were distributed to the arteries. It is postulated that the transmitter substance released at the autonomic nerve endings may have an effect upon the permeability of the venous sinusiods and the mobility of the blood cells in the marrow parenchyma resulting in their release into the circulating blood.

  1. Osteoprogenitor cells from bone marrow and cortical bone: understanding how the environment affects their fate.

    PubMed

    Corradetti, Bruna; Taraballi, Francesca; Powell, Sebastian; Sung, David; Minardi, Silvia; Ferrari, Mauro; Weiner, Bradley K; Tasciotti, Ennio

    2015-05-01

    Bone is a dynamic organ where skeletal progenitors and hematopoietic cells share and compete for space. Presumptive mesenchymal stem cells (MSC) have been identified and harvested from the bone marrow (BM-MSC) and cortical bone fragments (CBF-MSC). In this study, we demonstrate that despite the cells sharing a common ancestor, the differences in the structural properties of the resident tissues affect cell behavior and prime them to react differently to stimuli. Similarly to the bone marrow, the cortical portion of the bone contains a unique subset of cells that stains positively for the common MSC-associated markers. These cells display different multipotent differentiation capability, clonogenic expansion, and immunosuppressive potential. In particular, when compared with BM-MSC, CBF-MSC are bigger in size, show a lower proliferation rate at early passages, have a greater commitment toward the osteogenic lineage, constitutively produce nitric oxide as a mediator for bone remodeling, and more readily respond to proinflammatory cytokines. Our data suggest that the effect of the tissue's microenvironment makes the CBF-MSC a superior candidate in the development of new strategies for bone repair.

  2. A T Cell View of the Bone Marrow

    PubMed Central

    Bonomo, Adriana; Monteiro, Ana Carolina; Gonçalves-Silva, Triciana; Cordeiro-Spinetti, Eric; Galvani, Rômulo Gonçalves; Balduino, Alex

    2016-01-01

    The majority of T cells present in the bone marrow (BM) represent an activated/memory phenotype and most of these, if not all, are circulating T cells. Their lodging in the BM keeps them activated, turning the BM microenvironment into a “memory reservoir.” This article will focus on how T cell activation in the BM results in both direct and indirect effects on the hematopoiesis. The hematopoietic stem cell niche will be presented, with its main components and organization, along with the role played by T lymphocytes in basal and pathologic conditions and their effect on the bone remodeling process. Also discussed herein will be how “normal” bone mass peak is achieved only in the presence of an intact adaptive immune system, with T and B cells playing critical roles in this process. Our main hypothesis is that the partnership between T cells and cells of the BM microenvironment orchestrates numerous processes regulating immunity, hematopoiesis, and bone remodeling. PMID:27242791

  3. Recovery of hair coat color in Gray Collie (cyclic neutropenia)-normal bone marrow transplant chimeras.

    PubMed Central

    Yang, T. J.

    1978-01-01

    Gray Collie-normal bone marrow transplantation chimeras showed normal coloration of the hair coat on tails and several other areas 2 years after successful transplantation of bone marrow to correct cyclic neutropenia of the Gray Collie syndrome. Images Figures 1-2 PMID:347941

  4. Microdosimetry of astatine-211 using histological images: application to bone marrow.

    PubMed

    Akabani, G; Zalutsky, M R

    1997-12-01

    A method is presented for calculating the small-scale dosimetry of 211At in red bone marrow using chord-length distributions obtained from digitized histological images. This study used histological samples of bone marrow from beagle dogs to convey morphological information about cell conglomerations within bone marrow. Two 211At activity distributions were considered within the extracellular fluid and the surface of red bone marrow cells. Results confirmed the influence of cell conglomeration and activity distribution in determining the microdosimetry of red bone marrow. Average S* values of 1.6 x 10(-9) and 1.90 x 10(-9) Gy g Bq(-1) s(-1) were calculated for activity distributions located within the extracellular fluid and the surface of red bone marrow cells, respectively. The cumulated activity required to reduce survival probability to 0.37 also was calculated as a function of cell sensitivity for both activity distributions. The activity distribution on the cell surface resulted in a higher cell-killing efficiency, requiring a lower activity concentration of approximately 25% when compared with activity located in the extracellular fluid. Of relevance to potential clinical studies with 211At, the probability for zero hits for red bone marrow cells was > 10% for cumulated activities of less than 5.5 x 10(8) Bq s g(-1) in bone marrow.

  5. Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment.

    PubMed

    Ponzetta, Andrea; Benigni, Giorgia; Antonangeli, Fabrizio; Sciumè, Giuseppe; Sanseviero, Emilio; Zingoni, Alessandra; Ricciardi, Maria Rosaria; Petrucci, Maria Teresa; Santoni, Angela; Bernardini, Giovanni

    2015-11-15

    Natural killer (NK) cells are key innate immune effectors against multiple myeloma, their activity declining in multiple myeloma patients with disease progression. To identify the mechanisms underlying NK cell functional impairment, we characterized the distribution of functionally distinct NK cell subsets in the bone marrow of multiple myeloma-bearing mice. Herein we report that the number of KLRG1(-) NK cells endowed with potent effector function rapidly and selectively decreases in bone marrow during multiple myeloma growth, this correlating with decreased bone marrow NK cell degranulation in vivo. Altered NK cell subset distribution was dependent on skewed chemokine/chemokine receptor axes in the multiple myeloma microenvironment, with rapid downmodulation of the chemokine receptor CXCR3 on NK cells, increased CXCL9 and CXCL10, and decreased CXCL12 expression in bone marrow. Similar alterations in chemokine receptor/chemokine axes were observed in patients with multiple myeloma. Adoptive transfer experiments demonstrated that KLRG1(-) NK cell migration to the bone marrow was more efficient in healthy than multiple myeloma-bearing mice. Furthermore, bone marrow localization of transferred CXCR3-deficient NK cells with respect to wild type was enhanced in healthy and multiple myeloma-bearing mice, suggesting that CXCR3 restrains bone marrow NK cell trafficking. Our results indicate that multiple myeloma-promoted CXCR3 ligand upregulation together with CXCL12 downmodulation act as exit signals driving effector NK cells outside the bone marrow, thus weakening the antitumor immune response at the primary site of tumor growth.

  6. Postradiation recovery of human bone marrow and morphological dynamics of undifferentiated cell pool

    SciTech Connect

    Suvorova, L.A.; Vyalova, N.A.; Barabanoya, A.V.; Gruzdev, G.P.

    1982-01-01

    The postradiation repair of the hemopoietic function in human beings and of changes observed in bone marrow and peripheral blood is described. The processes of damage and recovery of bone marrow from acute radiation sickness induced by external radiation are described, based on observations of 77 samples made from the first to the forty-third day after irradiation.

  7. The Role of Bone Marrow Cells in the Phenotypic Changes Associated with Diabetic Nephropathy

    PubMed Central

    Yang, Guang; Cheng, Qingli; Liu, Sheng; Zhao, Jiahui

    2015-01-01

    The aim of our study was to investigate the role of bone marrow cells in the phenotypic changes that occur in diabetic nephropathy. Bone marrow cells were obtained from either streptozotocin-induced diabetic or untreated control C3H/He mice and transplanted into control C3H/He mice. Eight weeks after bone marrow cell transplantation, renal morphologic changes and clinical parameters of diabetic nephropathy, including the urine albumin/creatinine ratio and glucose tolerance, were measured in vivo. Expression levels of the genes encoding α1 type IV collagen and transforming growth factor-β1 in the kidney were assayed. Our results demonstrated that glucose tolerance was normal in the recipients of bone marrow transplants from both diabetic and control donors. However, compared with recipients of the control bone marrow transplant, the urinary albumin/creatinine ratio, glomerular size, and the mesangial/glomerular area ratio increased 3.3-fold (p < 0.01), 1.23-fold (p < 0.01), and 2.13-fold (p < 0.001), respectively, in the recipients of the diabetic bone marrow transplant. Expression levels of the genes encoding glomerular α1 type IV collagen and transforming growth factor-β1 were also significantly increased (p < 0.01) in the recipients of the diabetic bone marrow transplant. Our data suggest that bone marrow cells from the STZ-induced diabetic mice can confer a diabetic phenotype to recipient control mice without the presence of hyperglycemia. PMID:26340671

  8. A Novel Approach for Performing Bone Marrow Aspiration at the Time of Radical Prostatectomy

    PubMed Central

    Tosoian, Jeffrey J.; Reyes, Diane K.; Gorin, Michael A.; Hortopan, Steven; Partin, Alan W.; Pienta, Kenneth J.; Ross, Ashley E.; Schaeffer, Edward M.

    2016-01-01

    The bone marrow microenvironment represents a “metastatic niche” in which prostate cancer cells may persist and evade cytotoxic therapy. In order to study the biology of prostate cancer dissemination, we have established a safe and efficient method for performing pubic bone marrow aspiration at the time of radical prostatectomy. We herein describe our experience with this technique. PMID:27175343

  9. A Novel Approach for Performing Bone Marrow Aspiration at the Time of Radical Prostatectomy.

    PubMed

    Tosoian, Jeffrey J; Reyes, Diane K; Gorin, Michael A; Hortopan, Steven; Partin, Alan W; Pienta, Kenneth J; Ross, Ashley E; Schaeffer, Edward M

    2016-05-01

    The bone marrow microenvironment represents a "metastatic niche" in which prostate cancer cells may persist and evade cytotoxic therapy. In order to study the biology of prostate cancer dissemination, we have established a safe and efficient method for performing pubic bone marrow aspiration at the time of radical prostatectomy. We herein describe our experience with this technique.

  10. Knowledge and attitude of Lublin universities students' toward the opportunity of becoming unrelated bone marrow donor.

    PubMed

    Sikora, Agnieszka; Wiorkowski, Krzysztof; Szara, Paulina; Drabko, Katarzyna

    2014-01-01

    Hematopoietic Stem Cell Transplantation (HSCT) is a very important life-saving procedure to treat many disorders. In August 2014, there were more than 24.5 million donor registered in the Worldwide Bone Marrow Donor Register. In the Polish Register of Unrelated Bone Marrow and Umbilical Cord Blood Donors at the end of 2013 there were almost 540 thousand registered bone marrow donors. Despite increasing numbers of registered donors, the amount of requests also increased. It shows that the number of donors is still insufficient. The analysis of knowledge and attitude of Lublin universities students' toward the opportunity to become an unrelated bone marrow donor was the aim of our study. 1609 Lublin students from non-medical universities from different years and specializations of study, of both sexes, aged 19-35 took part in the survey. It consisted of 16 questions. There were knowledge-testing questions, and also personal ones. Among interviewees, 16% were registered as potential bone marrow donors. The reason for not being registered registration chosen most often was that the surveyed did not take this into consideration. Correct answers to all of the questions were given by 21% of students. The biggest number of incorrect answers was given to the question about a place from bone marrow is harvested - nearly 49%. Registered students showed a better level of knowledge than the unregistered. We noted a low level of knowledge about bone marrow donation and possibility of becoming potential bone marrow donor among Lublin universities students.

  11. Chlorpromazine-induced liver and bone marrow granulomas associated with agranulocytosis.

    PubMed

    Ben-Yehuda, A; Bloom, A; Lijovetzky, G; Flusser, D; Tur-Kaspa, R

    1990-08-01

    Chlorpromazine-induced liver damage is usually manifested by intrahepatic cholestasis. Hypoplastic bone marrow associated with agranulocytosis is a well-known side effect of chlorpromazine treatment. A 35-year-old woman with liver and bone marrow granulomas associated with agranulocytosis induced by chlorpromazine treatment is described.

  12. Regulatory pathways associated with bone loss and bone marrow adiposity caused by aging, chemotherapy, glucocorticoid therapy and radiotherapy.

    PubMed

    Georgiou, Kristen R; Hui, Susanta K; Xian, Cory J

    2012-01-01

    The bone marrow is a complex environment that houses haematopoietic and mesenchymal cell populations and regulates bone turnover throughout life. The high proliferative capacity of these cell populations however, makes them susceptible to damage and injury, altering the steady-state of the bone marrow environment. Following cancer chemotherapy, irradiation and long-term glucocorticoid use, reduced bone and increased fat formation of marrow stromal progenitor cells results in a fatty marrow cavity, reduced bone mass and increased fracture risk. These bone and marrow defects are also observed in age-related complications such as estrogen deficiency and increased oxidative stress. Although the underlying mechanisms are yet to be clarified, recent investigations have suggested a switch in lineage commitment of bone marrow mesenchymal stem cells down the adipogenic lineage at the expense of osteogenic differentiation following such stress or injury. The Wnt/β-catenin signalling pathway is however has been recognized the key mechanism regulating stromal commitment, and its involvement in the osteogenic and adipogenic lineage commitment switch under the damaging conditions has been of great interest. This article reviews the effects of various types of stress or injury on the commitment to the adipogenic and osteogenic lineages of bone marrow stromal progenitor cells, and summarizes the roles of the Wnt/β-catenin and associated signalling pathways in the lineage commitment, switch, and recovery after damage, and as a therapeutic target.

  13. Detection of micrometastatic prostate cancer cells in the bone marrow of patients with prostate cancer.

    PubMed Central

    Deguchi, T.; Yang, M.; Ehara, H.; Ito, S.; Nishino, Y.; Takahashi, Y.; Ito, Y.; Shimokawa, K.; Tanaka, T.; Imaeda, T.; Doi, T.; Kawada, Y.

    1997-01-01

    Thirty-five patients with prostate cancer were examined for micrometastases to the bone marrow using reverse transcription-polymerase chain reaction (RT-PCR) with primers specific for the prostate-specific antigen (PSA) gene. Of nine patients with bone metastases detectable by bone scan imaging, five patients had PSA mRNA expression in the bone marrow detectable by RT-PCR. Of 26 patients with negative bone scan findings, seven patients had PSA mRNA expression detectable in the bone marrow. RT-PCR could detect micrometastatic prostate cancer cells in the bone marrow that were not detectable by bone scan imaging. Of 16 patients with a serum PSA concentration of 25 ng ml(-1) or greater, only nine (56.3%) had bone metastases detected by bone scans. Of the remaining seven patients, five had micrometastases to the bone marrow detected by RT-PCR. Overall, 14 of 16 patients (87.5%) with a serum PSA concentration of 25 ng ml(-1) or greater had metastatic bone diseases including bone marrow micrometastases. Of 19 patients with a serum PSA concentration of less than 25 ng ml(-1), two (10.5%) had only micrometastatic disease detected by RT-PCR. A significant correlation was observed between the incidence of bone involvement and the serum PSA concentration. This study suggests that RT-PCR will potentially develop into a relevant tool to assess bone involvement including bone marrow micrometastases and establish a precise correlation between serum PSA concentration and metastatic bone disease in patients with prostate cancer. Images Figure 1 PMID:9043017

  14. PPARγ antagonist attenuates mouse immune-mediated bone marrow failure by inhibition of T cell function

    PubMed Central

    Sato, Kazuya; Feng, Xingmin; Chen, Jichun; Li, Jungang; Muranski, Pawel; Desierto, Marie J.; Keyvanfar, Keyvan; Malide, Daniela; Kajigaya, Sachiko; Young, Neal S.

    2016-01-01

    Acquired aplastic anemia is an immune-mediated disease, in which T cells target hematopoietic cells; at presentation, the bone marrow is replaced by fat. It was reported that bone marrow adipocytes were negative regulators of hematopoietic microenvironment. To examine the role of adipocytes in bone marrow failure, we investigated peroxisomal proliferator-activated receptor gamma, a key transcription factor in adipogenesis, utilizing an antagonist of this factor called bisphenol-A-diglycidyl-ether. While bisphenol-A-diglycidyl-ether inhibited adipogenesis as expected, it also suppressed T cell infiltration of bone marrow, reduced plasma inflammatory cytokines, decreased expression of multiple inflammasome genes, and ameliorated marrow failure. In vitro, bisphenol-A-diglycidyl-ether suppressed activation and proliferation, and reduced phospholipase C gamma 1 and nuclear factor of activated T-cells 1 expression, as well as inhibiting calcium flux in T cells. The in vivo effect of bisphenol-A-diglycidyl-ether on T cells was confirmed in a second immune-mediated bone marrow failure model, using different strains and non-major histocompatibility antigen mismatched: bisphenol-A-diglycidyl-ether ameliorated marrow failure by inhibition of T cell infiltration of bone marrow. Our data indicate that peroxisomal proliferator-activated receptor gamma antagonists may attenuate murine immune-mediated bone marrow failure, at least in part, by suppression of T cell activation, which might hold implications in the application of peroxisomal proliferator-activated receptor gamma antagonists in immune-mediated pathophysiologies, both in the laboratory and in the clinic. Genetically “fatless” mice developed bone marrow failure with accumulation of marrow adipocytes in our model, even in the absence of body fat, suggesting different mechanisms of systematic and marrow adipogenesis and physiologic versus pathophysiologic fat accumulation. PMID:26589913

  15. PPARγ antagonist attenuates mouse immune-mediated bone marrow failure by inhibition of T cell function.

    PubMed

    Sato, Kazuya; Feng, Xingmin; Chen, Jichun; Li, Jungang; Muranski, Pawel; Desierto, Marie J; Keyvanfar, Keyvan; Malide, Daniela; Kajigaya, Sachiko; Young, Neal S

    2016-01-01

    Acquired aplastic anemia is an immune-mediated disease, in which T cells target hematopoietic cells; at presentation, the bone marrow is replaced by fat. It was reported that bone marrow adipocytes were negative regulators of hematopoietic microenvironment. To examine the role of adipocytes in bone marrow failure, we investigated peroxisomal proliferator-activated receptor gamma, a key transcription factor in adipogenesis, utilizing an antagonist of this factor called bisphenol-A-diglycidyl-ether. While bisphenol-A-diglycidyl-ether inhibited adipogenesis as expected, it also suppressed T cell infiltration of bone marrow, reduced plasma inflammatory cytokines, decreased expression of multiple inflammasome genes, and ameliorated marrow failure. In vitro, bisphenol-A-diglycidyl-ether suppressed activation and proliferation, and reduced phospholipase C gamma 1 and nuclear factor of activated T-cells 1 expression, as well as inhibiting calcium flux in T cells. The in vivo effect of bisphenol-A-diglycidyl-ether on T cells was confirmed in a second immune-mediated bone marrow failure model, using different strains and non-major histocompatibility antigen mismatched: bisphenol-A-diglycidyl-ether ameliorated marrow failure by inhibition of T cell infiltration of bone marrow. Our data indicate that peroxisomal proliferator-activated receptor gamma antagonists may attenuate murine immune-mediated bone marrow failure, at least in part, by suppression of T cell activation, which might hold implications in the application of peroxisomal proliferator-activated receptor gamma antagonists in immune-mediated pathophysiologies, both in the laboratory and in the clinic. Genetically "fatless" mice developed bone marrow failure with accumulation of marrow adipocytes in our model, even in the absence of body fat, suggesting different mechanisms of systematic and marrow adipogenesis and physiologic versus pathophysiologic fat accumulation.

  16. 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.

  17. Autologous antibodies that bind neuroblastoma cells.

    PubMed

    Sun, Yujing; Sholler, Giselle S; Shukla, Girja S; Pero, Stephanie C; Carman, Chelsea L; Zhao, Ping; Krag, David N

    2015-11-01

    Antibody therapy of neuroblastoma is promising and our goal is to derive antibodies from patients with neuroblastoma for developing new therapeutic antibodies. The feasibility of using residual bone marrow obtained for clinical indications as a source of tumor cells and a source of antibodies was assessed. From marrow samples, neuroblastoma cells were recovered, grown in cell culture and also implanted into mice to create xenografts. Mononuclear cells from the marrow were used as a source to generate phage display antibody libraries and also hybridomas. Growth of neuroblastoma patient cells was possible both in vitro and as xenografts. Antibodies from the phage libraries and from the monoclonal hybridomas bound autologous neuroblastoma cells with some selectivity. It appears feasible to recover neuroblastoma cells from residual marrow specimens and to generate human antibodies that bind autologous neuroblastoma cells. Expansion of this approach is underway to collect more specimens, optimize methods to generate antibodies, and to evaluate the bioactivity of neuroblastoma-binding antibodies.

  18. Primary bone marrow B-cell non-Hodgkin's lymphoma successfully treated with R-CHOP.

    PubMed

    Qian, Liren; Zhang, Zhi; Shen, Jianliang; Liu, Yi

    2013-01-01

    Primary isolated bone marrow disease as a presenting feature of lymphoma is very rare. We describe the case of a Chinese with isolated bone marrow small B-cell lymphoma as a first manifestation. A 55-year old woman was admitted to our hospital with fever. Her peripheral blood smear and laboratory findings were suggestive of bicytopenia. Bone marrow specimen showed diffusely distributed small-sized lymphocytes. Combined with immunophenotypic and chromosomal analysis, a diagnosis of primary bone marrow B-cell non-Hodgkin's lymphoma was made. The patient was treated with R-CHOP (rituximab and cyclophosphamide, epirubicin, vindesine, and prednisone) regimen for six cycles. She had complete remission and is still alive without relapse. We concluded that primary bone marrow mature small B-cell lymphoma is a rare but distinctive subtype of lymphoma. The prognosis for this entity is poor but rituximab-based treatment is promising for improving its outcomes.

  19. High-fidelity organic preservation of bone marrow in ca. 10 Ma amphibians

    NASA Astrophysics Data System (ADS)

    McNamara, Maria E.; Orr, Patrick J.; Kearns, Stuart L.; Alcalá, Luis; Anadón, Pere; Peñalver-Mollá, Enrique

    2006-08-01

    Bone marrow in ca. 10 Ma frogs and salamanders from the Miocene of Libros, Spain, represents the first fossilized example of this extremely decay-prone tissue. The bone marrow, preserved in three dimensions as an organic residue, retains the original texture and red and yellow color of hematopoietic and fatty marrow, respectively; moldic osteoclasts and vascular structures are also present. We attribute exceptional preservation of the fossilized bone marrow to cryptic preservation: the bones of the amphibians formed protective microenvironments, and inhibited microbial infiltration. Specimens in which bone marrow is preserved vary in their completeness and articulation and in the extent to which the body outline is preserved as a thin film of organically preserved bacteria. Cryptic preservation of these labile tissues is thus to a large extent independent of, and cannot be predicted by, the taphonomic history of the remainder of the specimen.

  20. Composite vascularized skin/bone graft model: a viable source for vascularized bone marrow transplantation.

    PubMed

    Siemionow, Maria; Ulusal, Betul G; Ozmen, Selahattin; Ulusal, Ali E; Ozer, Kagan

    2004-01-01

    In this study, we introduce a new model for vascularized skin and bone marrow transplantation. Twenty-five Lewis (RT1(1)) rats were studied. Anatomic dissection studies were performed in 5 animals. In the experimental group, 10 isograft transplantations were performed between Lewis rats. Combined groin skin and femoral bone flaps were transplanted based on the femoral artery and vein. Transplants were evaluated on a daily basis. All flaps survived without problems over 100 days posttransplant. The skin component remained pink and pliable, and grew new hair. Histological examination of the femoral bone (except the femoral head) revealed active hematopoiesis with a viable compact and cancellous bone components on day 100 posttransplant. This model can be applied to tolerance induction studies across the major Histocompatibility (MHC) barrier, where bone will serve as donor of stem and progenitor cells, and the skin flap will serve as a monitor of graft rejection.

  1. Allogenous bone grafts improved by bone marrow stem cells and platelet growth factors: clinical case reports.

    PubMed

    Filho Cerruti, Humberto; Kerkis, Irina; Kerkis, Alexandre; Tatsui, Nelson Hidekazu; da Costa Neves, Adriana; Bueno, Daniela Franco; da Silva, Marcelo Cavenaghi Pereira

    2007-04-01

    In order to increase the amount of available bone where dental implants must be placed, the present study has associated platelet-rich plasma (PRP) and mononuclear cells (MNCs) from bone marrow aspirate and bone scaffold (BS) in 32 patients aged between 45 and 75 years old. The MNC attainment and the adherence to the BS were confirmed through histology, cell culture, and scanning electron microscopy. The clinical results, analyzed by computed tomography, have showed that the scaffolds were well integrated and adapted to the cortical bone. We can conclude that the process of healing observed in the patients was due to the presence of mesenchymal stem cell in MNC fraction in the bone grafts.

  2. Bone marrow segmentation based on a combined consideration of transverse relaxation processes and Dixon oscillations.

    PubMed

    Balasubramanian, Mukund; Jarrett, Delma Y; Mulkern, Robert V

    2016-05-01

    The aim of this study was to demonstrate that gradient-echo sampling of single spin echoes can be used to isolate the signal from trabecular bone marrow, with high-quality segmentation and surface reconstructions resulting from the application of simple post-processing strategies. Theoretical expressions of the time-domain single-spin-echo signal were used to simulate signals from bone marrow, non-bone fatty deposits and muscle. These simulations were compared with and used to interpret signals obtained by the application of the gradient-echo sampling of a spin-echo sequence to image the knee and surrounding tissues at 1.5 T. Trabecular bone marrow has a much higher reversible transverse relaxation rate than surrounding non-bone fatty deposits and other musculoskeletal tissues. This observation, combined with a choice of gradient-echo spacing that accentuates Dixon-type oscillations from chemical-shift interference effects, enabled the isolation of bone marrow signal from surrounding tissues through the use of simple image subtraction and thresholding. Three-dimensional renderings of the marrow surface were then readily generated with this approach - renderings that may prove useful for bone morphology assessment, e.g. for the measurement of femoral anteversion. In conclusion, understanding the behavior of signals from bone marrow and surrounding tissue as a function of time through a spin echo facilitates the segmentation and reconstruction of bone marrow surfaces using straightforward post-processing strategies that are typically available on modern radiology workstations.

  3. High-fat diet causes bone loss in young mice by promoting osteoclastogenesis through alteration of the bone marrow environment.

    PubMed

    Shu, Lei; Beier, Eric; Sheu, Tzong; Zhang, Hengwei; Zuscik, Michael J; Puzas, Edward J; Boyce, Brendan F; Mooney, Robert A; Xing, Lianping

    2015-04-01

    Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks of HFD treatment. After 6 and 12 weeks, HFD-exposed mice had less bone mass and increased osteoclast numbers. Bone marrow cells, but not spleen cells, from HFD-fed mice had increased osteoclast precursor frequency, elevated osteoclast formation, and bone resorption activity, as well as increased expression of osteoclastogenic regulators including RANKL, TNF, and PPAR-gamma. Bone formation rate and osteoblast and adipocyte numbers were also increased in HFD-fed mice. Isolated bone marrow cells also had a corresponding elevation in the expression of positive regulators of osteoblast and adipocyte differentiation. Our findings indicate that in juvenile mice, HFD-induced bone loss is mainly due to increased osteoclast bone resorption by affecting the bone marrow microenvironment. Thus, targeting osteoclast formation may present a new therapeutic approach for bone complications in obese children.

  4. Osteofibrous Dysplasia managed with Extraperiosteal excision, Autologous free fibular graft and bone graft substitute

    PubMed Central

    Abraham, Vineet T; Marimuthu, Chandrasekaran; Subbaraj, Ravichandran; Rengarajan, Nandakumar

    2015-01-01

    Introduction: Osteofibrous Dysplasia is a rare benign self-limiting fibro-osseous lesion most commonly seen in the diaphysis of the tibia. Its incidence is reported to be 0.2% of all primary bone tumors. It occurs in the first two decades of life with a slight male preponderance. Surgical options include extra periosteal resection, autologous graft, limb lengthening procedures etc. There are no case reports mentioning the use of synthetic bone graft to fill the defect following extraperiosteal excision. Case Report: A 13 year old girl presented with pain and swelling of the (R) leg since 2 months following a trivial injury at school. Examination revealed a 5×3cm tender swelling on the anteromedial aspect of the middle third tibia. Radiographs and MRI, revealed an eccentric expansile lytic lesion, which was multilocular and was present at the junction of the metaphysis and diaphysis on the antero -medial aspect of tibia. The cortex had ballooned out and there was a possibility of an impending fracture. Biopsy was done which revealed osteofibrous dysplasia. We did an extraperiosteal excision of the lesion. To fill the cavity we harvested 10 cm of the contralateral fibula and since there was still space in the cavity, we packed bone graft substitute (hydroxyapatite crystals) into the defect. The surgical management of osteofibrous dysplasia is controversial. Various methods of treatment of such cases have been described in literature. The use of synthetic graft is an option in these patients as it reduces morbidity; and in our case we had good graft incorporation with this method. Conclusion: Extraperiosteal Excision of Osteofibrous dysplasia combined with autologous free fibular graft and bone graft substitute is a good surgical option to prevent recurrence and mange bone defects in this rare lesion. PMID:27299018

  5. Bone turnover markers in peripheral blood and marrow plasma reflect trabecular bone loss but not endocortical expansion in aging mice.

    PubMed

    Shahnazari, Mohammad; Dwyer, Denise; Chu, Vivian; Asuncion, Frank; Stolina, Marina; Ominsky, Michael; Kostenuik, Paul; Halloran, Bernard

    2012-03-01

    We examined age-related changes in biochemical markers and regulators of osteoblast and osteoclast activity in C57BL/6 mice to assess their utility in explaining age-related changes in bone. Several recently discovered regulators of osteoclasts and osteoblasts were also measured to assess concordance between their systemic levels versus their levels in marrow plasma, to which bone cells are directly exposed. MicroCT of 6-, 12-, and 24-month-old mice indicated an early age-related loss of trabecular bone volume and surface, followed by endocortical bone loss and periosteal expansion. Trabecular bone loss temporally correlated with reductions in biomarkers of bone formation and resorption in both peripheral blood and bone marrow. Endocortical bone loss and periosteal bone gain were not reflected in these protein biomarkers, but were well correlated with increased expression of osteocalcin, rank, tracp5b, and cathepsinK in RNA extracted from cortical bone. While age-related changes in bone turnover markers remained concordant in blood versus marrow, aging led to divergent changes in blood versus marrow for the bone cell regulators RANKL, OPG, sclerostin, DKK1, and serotonin. Bone expression of runx2 and osterix increased progressively with aging and was associated with an increase in the number of osteoprogenitors and osteoclast precursors. In summary, levels of biochemical markers of bone turnover in blood and bone marrow plasma were predictive of an age-related loss of trabecular surfaces in adult C57BL/6 mice, but did not predict gains in cortical surfaces resulting from cortical expansion. Unlike these turnover markers, a panel of bone cell regulatory proteins exhibited divergent age-related changes in marrow versus peripheral blood, suggesting that their circulating levels may not reflect local levels to which osteoclasts and osteoblasts are directly exposed.

  6. CCN1 enhances angiogenic potency of bone marrow transplantation in a rat model of hindlimb ischemia.

    PubMed

    Yin, Cunping; Liang, Yuan; Guo, Shuguang; Zhou, Xingli; Pan, Xinghua

    2014-09-01

    Implantation of autologous bone marrow mononuclear cells (BM-MNCs) has been performed in ischemic tissues, for stimulation of angiogenesis, but the limited number of BM-MNCs in patients with hindlimb ischemia disease may offset their overall therapeutic efficacy. CCN1 is a novel and essential regulator during angiogenesis. We evaluated whether CCN1 and BM-MNC are capable of promoting angiogenesis in hindlimb ischemia. In this study, we created the rat model of hindlimb ischemia, and then the rats were randomly divided into four groups: CCN1 infusion plus BM-MNC transplantation (CCN1 + BM-MNCs group), CCN1 infusion plus PBS injection (CCN1 group), vehicle infusion plus BM-MNC transplantation (BM-MNCs group) and vehicle infusion plus PBS injection (control group). The combination of CCN1 and BM-MNC therapy could increase blood perfusion, capillary/muscle fiber ratio and tissue oxygenation in ischemic hindlimb. Moreover, CCN1 could not only inhibit the apoptosis of BM-MNCs, but also enhance the adhesiveness of BM-MNCs to HUVEC. Taken together, CCN1 enhanced angiogenesis of BM-MNC transplantation, and combining CCN1 with BM-MNC transplantation is a useful alternative for ischemic limbs.

  7. Therapeutic action of bone marrow-derived stem cells against acute kidney injury.

    PubMed

    Liu, Pengfei; Feng, Yetong; Wang, Yi; Zhou, Yulai

    2014-10-12

    Acute kidney injury (AKI) is a frequent clinical disease with a high morbidity rate and mortality rate, while the treatment options for this intractable disease are limited currently. In recent years, bone marrow-derived mesenchymal stem cells (BMSCs) have been demonstrated to hold an effect therapeutic action against AKI by scientists gradually, and the cells are capable to localize to renal compartments and contribute to kidney regeneration though differentiation or paracrine action. Especially, the advantages of BMSCs, such as low toxicity and side effect as well as autologous transplantation, endue the cell with a promising potential in clinical therapy against AKI. In this review, we mainly provide a concise overview of the application of BMSCs in the treatment of AKI, and summarize a series of published data regarding the mechanisms and optimizations of the BMSC-based therapy in renal repair after AKI. Even though some critical points about the BMSC-based therapy model still need clarification, we hope to develop more reliable pharmacological or biotechnical strategies utilizing the stem cell for the eventual treatment of humans with AKI, based on these studies and the understanding of mechanism of renal protection by BMSCs.

  8. Delayed minimally invasive injection of allogenic bone marrow stromal cell sheets regenerates large bone defects in an ovine preclinical animal model.

    PubMed

    Berner, Arne; Henkel, Jan; Woodruff, Maria A; Steck, Roland; Nerlich, Michael; Schuetz, Michael A; Hutmacher, Dietmar W

    2015-05-01

    Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future.

  9. Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction

    PubMed Central

    Dufrane, Denis; Docquier, Pierre-Louis; Delloye, Christian; Poirel, Hélène A.; André, Wivine; Aouassar, Najima

    2015-01-01

    Abstract Long bone nonunion in the context of congenital pseudarthrosis or carcinologic resection (with intercalary bone allograft implantation) is one of the most challenging pathologies in pediatric orthopedics. Autologous cancellous bone remains the gold standard in this context of long bone nonunion reconstruction, but with several clinical limitations. We then assessed the feasibility and safety of human autologous scaffold-free osteogenic 3-dimensional (3D) graft (derived from autologous adipose-derived stem cells [ASCs]) to cure a bone nonunion in extreme clinical and pathophysiological conditions. Human ASCs (obtained from subcutaneous adipose tissue of 6 patients and expanded up to passage 4) were incubated in osteogenic media and supplemented with demineralized bone matrix to obtain the scaffold-free 3D osteogenic structure as confirmed in vitro by histomorphometry for osteogenesis and mineralization. The 3D “bone-like” structure was finally transplanted for 3 patients with bone tumor and 3 patients with bone pseudarthrosis (2 congenital, 1 acquired) to assess the clinical feasibility, safety, and efficacy. Although minor clones with structural aberrations (aneuploidies, such as tri or tetraploidies or clonal trisomy 7 in 6%–20% of cells) were detected in the undifferentiated ASCs at passage 4, the osteogenic differentiation significantly reduced these clonal anomalies. The final osteogenic product was stable, did not rupture with forceps manipulation, did not induce donor site morbidity, and was easily implanted directly into the bone defect. No acute (<3 mo) side effects, such as impaired wound healing, pain, inflammatory reaction, and infection, or long-term side effects, such as tumor development, were associated with the graft up to 4 years after transplantation. We report for the first time that autologous ASC can be fully differentiated into a 3D osteogenic-like implant without any scaffold. We demonstrated that this engineered tissue can

  10. Mastoid Obliteration with Autologous Bone in Mastoidectomy Canal Wall Down Surgery: a Literature Overview

    PubMed Central

    Alves, Ricardo Dourado; Cabral Junior, Francisco; Fonseca, Anna Carolina de Oliveira; Bento, Ricardo Ferreira

    2015-01-01

    Introduction The objectives of mastoidectomy in cholesteatoma are a disease-free and dry ear, the prevention of recurrent disease, and the maintenance of hearing or the possibility to reconstruct an affected hearing mechanism. Canal wall down mastoidectomy has been traditionally used to achieve those goals with greater or lesser degrees of success. However, canal wall down is an aggressive approach, as it involves creating an open cavity and changing the anatomy and physiology of the middle ear and mastoid. A canal wall up technique eliminates the need to destroy the middle ear and mastoid, but is associated with a higher rate of residual cholesteatoma. The obliteration technics arise as an effort to avoid the disadvantages of both techniques. Objectives Evaluate the effectiveness of the mastoid obliteration with autologous bone in mastoidectomy surgery with canal wall down for chronic otitis, with or without cholesteatoma. Data Synthesis We analyzed nine studies of case series comprehending similar surgery techniques on 1017 total cases of operated ears in both adults and children, with at least 12 months follow-up. Conclusion Mastoid Obliteration with autologous bone has been utilized for many years to present date, and it seems to be safe, low-cost, with low recurrence rates - similar to traditional canal wall down procedures and with greater water resistance and quality of life improvements. PMID:26722350

  11. Mastoid Obliteration with Autologous Bone in Mastoidectomy Canal Wall Down Surgery: a Literature Overview.

    PubMed

    Alves, Ricardo Dourado; Cabral Junior, Francisco; Fonseca, Anna Carolina de Oliveira; Bento, Ricardo Ferreira

    2016-01-01

    Introduction The objectives of mastoidectomy in cholesteatoma are a disease-free and dry ear, the prevention of recurrent disease, and the maintenance of hearing or the possibility to reconstruct an affected hearing mechanism. Canal wall down mastoidectomy has been traditionally used to achieve those goals with greater or lesser degrees of success. However, canal wall down is an aggressive approach, as it involves creating an open cavity and changing the anatomy and physiology of the middle ear and mastoid. A canal wall up technique eliminates the need to destroy the middle ear and mastoid, but is associated with a higher rate of residual cholesteatoma. The obliteration technics arise as an effort to avoid the disadvantages of both techniques. Objectives Evaluate the effectiveness of the mastoid obliteration with autologous bone in mastoidectomy surgery with canal wall down for chronic otitis, with or without cholesteatoma. Data Synthesis We analyzed nine studies of case series comprehending similar surgery techniques on 1017 total cases of operated ears in both adults and children, with at least 12 months follow-up. Conclusion Mastoid Obliteration with autologous bone has been utilized for many years to present date, and it seems to be safe, low-cost, with low recurrence rates - similar to traditional canal wall down procedures and with greater water resistance and quality of life improvements.

  12. Ectopic bone regeneration by human bone marrow mononucleated cells, undifferentiated and osteogenically differentiated bone marrow mesenchymal stem cells in beta-tricalcium phosphate scaffolds.

    PubMed

    Ye, Xinhai; Yin, Xiaofan; Yang, Dawei; Tan, Jian; Liu, Guangpeng

    2012-07-01

    Tissue engineering approaches using the combination of porous ceramics and bone marrow mesenchymal stem cells (BMSCs) represent a promising bone substitute for repairing large bone defects. Nevertheless, optimal conditions for constructing tissue-engineered bone have yet to be determined. It remains unclear if transplantation of predifferentiated BMSCs is superior to undifferentiated BMSCs or freshly isolated bone marrow mononucleated cells (BMNCs) in terms of new bone formation in vivo. The aim of this study was to investigate the effect of in vitro osteogenic differentiation (β-glycerophosphate, dexamethasone, and l-ascorbic acid) of human BMSCs on the capability to form tissue-engineered bone in unloaded conditions after subcutaneous implantation in nude mice. After isolation from human bone marrow aspirates, BMNCs were divided into three parts: one part was seeded onto porous beta-tricalcium phosphate ceramics immediately and transplanted in a heterotopic nude mice model; two parts were expanded in vitro to passage 2 before cell seeding and in vivo transplantation, either under osteogenic conditions or not. Animals were sacrificed for micro-CT and histological evaluation at 4, 8, 12, 16, and 20 weeks postimplantation. The results showed that BMSCs differentiated into osteo-progenitor cells after induction, as evidenced by the altered cell morphology and elevated alkaline phosphatase activity and calcium deposition, but their clonogenicity, proliferating rate, and seeding efficacy were not significantly affected by osteogenic differentiation, compared with undifferentiated cells. Extensive new bone formed in the pores of all the scaffolds seeded with predifferentiated BMSCs at 4 weeks after implantation, and maintained for 20 weeks. On the contrary, scaffolds containing undifferentiated BMSCs revealed limited bone formation only in 1 out of 6 cases at 8 weeks, and maintained for 4 weeks. For scaffolds with BMNCs, woven bone was observed sporadically only in one

  13. Treatment of simple bone