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Sample records for allogeneic demineralized bone

  1. Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury.

    PubMed

    Man, Zhentao; Hu, Xiaoqing; Liu, Zhenlong; Huang, Hongjie; Meng, Qingyang; Zhang, Xin; Dai, Linghui; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Zhou, Chunyan; Ao, Yingfang

    2016-11-01

    Cartilage tissue engineering is the hotspot of cartilage repair. The allogenic chondrocytes appear to be a promising source of seed cells in cartilage tissue engineering. In this study, we aimed to transplant allogenic chondrocytes with chitosan hydrogel (CS)-demineralized bone matrix (DBM) hybrid scaffold (CS/DBM) to repair rabbit cartilage injury with one-step operation. After the CS/DBM scaffold was successfully fabricated, it showed that the porous CS filled the large pores of DBM, which improved the distribution of seed cells in the CS/DBM scaffold. The allogenic chondrocytes at second passage were transplanted with different scaffolds to repair rabbit cartilage injury. Twenty-four weeks after surgery, the cartilage defect in the CS/DBM group was successfully filled as shown by MRI. Moreover, the histological score of CS/DBM group was significantly higher than that of the other groups. On the aspect of biomechanical property, the regenerated cartilage in the CS/DBM group were superior to those in the other groups as determined by nanoindentation. Meanwhile, no obvious inflammatory response was observed after the transplantation of allogenic chondrocytes at 24 weeks post-surgery. Furtherly, gene expression profile for cells within the repair tissue was compared with the allogenic chondrocytes before transplantation using Agilent microarray and RT-qPCR. The results showed that some genes beneficial to cartilage regeneration, such as BMP-7, HGF, and IGF-1, were upregulated one month after transplantation. Consequently, our study demonstrated that the transplantation of allogenic chondrocytes with CS/DBM scaffold successfully repaired rabbit cartilage injury with only one-step operation, thereby providing new insights into cartilage tissue engineering. PMID:27636153

  2. Research opportunities in bone demineralization, phase 3

    NASA Technical Reports Server (NTRS)

    Anderson, S. A. (Editor); Cohn, S. H. (Editor)

    1984-01-01

    An overview of bone demineralization during space flight, observations in bone demineralization and experiments related to bone loss planned for Spacelab flights, and suggestions for further research are investigated. The observations of the working group focused upon the following topics: (1) pathogenesis of bone demineralization, (2) potential for occurrence of renal stones consequent to prolonged hypercalciuria, (3) development of appropriate ground based and inflight models to study bone demineralization, (4) integration of research efforts, and (5) development of effective countermeasures.

  3. Experiment M-6: Bone Demineralization

    NASA Technical Reports Server (NTRS)

    Mack, Pauline B.; Vose, George; Vogt, Fred B.; LaChance, Paul A.

    1966-01-01

    Densitometric evaluations of serial radiographs of "normal" subjects have often shown rather frequent changes in bone mass within relatively short periods of time. For this reason it was decided to make two pre-flight and two post flight radiographs of the Gemini V backup crew. In comparing the changes observed preflight and post flight as the conventional os calcis scanning site between the two crews, it was found that no changes greater than 4 percent were evident in either member of the backup crew. In comparing the changes observed preflight and postflight as the conventional o calcis scanning site between the two crews, it was found that no changes greater than 4 percent were evident in either member of the backup crew. This is in contract to the 15.1 and 8.9 percent losses observed in the prime crew. It has long been known that the skeletal system experiences a general loss of mineral under immobilization or extended bed rest. However, in both Gemini IV and Gemini V studies, bone mass losses were greater in both the os calcis and phalanx than were shown by the TWU bed-rest subjects during the same period of time. Although the bone mass losses in the 8-day Gemini V flight were generally greater than in the 4-day Gemini IV flight, the information to date is still insufficient to conclude that the losses tend to progress linearly with time, or whether a form of physiological adaptation may occur in longer space flights.

  4. Bone protein extraction without demineralization utilizing principles from hydroxyapatite chromatography

    PubMed Central

    Cleland, Timothy P.; Vashishth, Deepak

    2014-01-01

    Historically, extraction of bone proteins has relied on the use of demineralization to better retrieve proteins from the extracellular matrix; however, demineralization can be a slow process that restricts subsequent analysis of the samples. Here, we developed a novel protein extraction method that does not use demineralization, but utilizes a methodology from hydroxyapatite chromatography where high concentrations of ammonium phosphate and ammonium bicarbonate are used to extract bone proteins. We report that this method has a higher yield than previously published small-scale extant bone extractions, with and without demineralization. Furthermore, after digestion with trypsin and subsequent HPLC-MS/MS analysis, we were able to detect several extracellular matrix and vascular proteins in addition to collagen I and osteocalcin. Our new method has the potential to isolate proteins in a short period (4 hrs) and provide information about bone proteins that may be lost during demineralization or with the use of denaturing agents. PMID:25535955

  5. Bone Induction by Demineralized Dentin Matrix in Nude Mouse Muscles

    PubMed Central

    Kim, Kyung-Wook

    2014-01-01

    Purpose: This study examined the osteoinductive activity of demineralized human dentin matrix for nude mice. Methods: Twenty healthy nude mice weighing about 15 to 20 g were used for study. Demineralized human dentin matrix was prepared and implanted into the dorsal portion of nude mice (subcutaneous), which were sacrificed at two, four, and eight weeks after demineralized dentin matrix grafting and evaluated histologically by H&E and Masson trichrome staining. The specimens were also evaluated histomorphometrically. Results: The demineralized dentin matrix induced bone and cartilage formation independently in soft tissues. Histological examination showed bone-forming cells such as osteoblasts and fibroblasts at two, four, and eight weeks. Conclusion: These results suggest that demineralized human dentin matrix has osteoinductive ability, and is a good alternative to autogenous bone graft materials. PMID:27489810

  6. Biomimetically enhanced demineralized bone matrix for bone regenerative applications

    PubMed Central

    Ravindran, Sriram; Huang, Chun-Chieh; Gajendrareddy, Praveen; Narayanan, Raghuvaran

    2015-01-01

    Demineralized bone matrix (DBM) is one of the most widely used bone graft materials in dentistry. However, the ability of DBM to reliably and predictably induce bone regeneration has always been a cause for concern. The quality of DBM varies greatly depending on several donor dependent factors and also manufacturing techniques. In order to standardize the quality and to enable reliable and predictable bone regeneration, we have generated a biomimetically-enhanced version of DBM (BE-DBM) using clinical grade commercial DBM as a control. We have generated the BE-DBM by incorporating a cell-derived pro-osteogenic extracellular matrix (ECM) within clinical grade DBM. In the present study, we have characterized the BE-DBM and evaluated its ability to induce osteogenic differentiation of human marrow derived stromal cells (HMSCs) with respect to clinical grade commercial DBM. Our results indicate that the BE-DBM contains significantly more pro-osteogenic factors than DBM and enhances HMSC differentiation and mineralized matrix formation in vitro and in vivo. Based on our results, we envision that the BE-DBM has the potential to replace DBM as the bone graft material of choice. PMID:26557093

  7. High efficiency DNA extraction from bone by total demineralization.

    PubMed

    Loreille, Odile M; Diegoli, Toni M; Irwin, Jodi A; Coble, Michael D; Parsons, Thomas J

    2007-06-01

    In historical cases, missing persons' identification, mass disasters, and ancient DNA investigations, bone and teeth samples are often the only, and almost always the best, biological material available for DNA typing. This is because of the physical and chemical barrier that the protein:mineral matrix of bone poses to environmental deterioration and biological attack. Most bone extraction protocols utilized in the forensic community involve an incubation period of bone powder in extraction buffer for proteinase digestion, followed by the collection of the supernatant, and the disposal of large quantities of undissolved bone powder. Here we present an extremely efficient protocol for recovery of DNA by complete demineralization, resulting in full physical dissolution of the bone sample. This is performed in a manner that retains and concentrates all the reagent volume, for complete DNA recovery. For our study, we selected 14 challenging bone samples. The bones were extracted side-by-side with our new demineralization protocol and the standard extraction protocol in use at AFDIL. A real-time quantification assay based on the amplification of a 143 bp mtDNA fragment showed that this new demineralization protocol significantly enhances the quantity of DNA that can be extracted and amplified from degraded skeletal remains. We have used this technique to successfully recover authentic DNA sequences from extremely challenging samples that failed repeatedly using the standard protocol.

  8. Physicomechanical properties of the extracellular matrix of a demineralized bone

    NASA Astrophysics Data System (ADS)

    Kirilova, I. A.; Sharkeev, Yu. P.; Nikolaev, S. V.; Podorozhnaya, V. T.; Uvarkin, P. V.; Ratushnyak, A. S.; Chebodaeva, V. V.

    2016-08-01

    The article describes the results of a study of physicomechanical properties of a demineralized bone matrix of human cancellous and compact bones. A demineralized cancellous bone was shown to have the best characteristics of a porous system for colonization of matrices by cells. The ultimate stress and elasticity modulus of samples of demineralized femoral heads isolated in primary hip replacement was demonstrated to vary in wide ranges. The elasticity modulus ranged from 50 to 250 MPa, and the tensile strength varied from 1.1 to 5.5 MPa. Microhardness measurements by the recovered indentation method were not possible because of the viscoelastic properties of a bone material. To study the piezoelectric properties of samples, a measuring system was developed that comprised a measuring chamber with contact electrodes, a system for controlled sample loading, an amplifier-converter unit, and signal recording and processing software. The measurement results were used to determine the dependence of the signal amplitude on the dynamic deformation characteristics. The findings are discussed in terms of the relationship between the mechanical and electrical properties and the structure of the organic bone component.

  9. A composite demineralized bone matrix--self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow.

    PubMed

    Hou, Tianyong; Li, Zhiqiang; Luo, Fei; Xie, Zhao; Wu, Xuehui; Xing, Junchao; Dong, Shiwu; Xu, Jianzhong

    2014-07-01

    The need for suitable bone grafts is high; however, there are limitations to all current graft sources, such as limited availability, the invasive harvest procedure, insufficient osteoinductive properties, poor biocompatibility, ethical problems, and degradation properties. The lack of osteoinductive properties is a common problem. As an allogenic bone graft, demineralized bone matrix (DBM) can overcome issues such as limited sources and comorbidities caused by invasive harvest; however, DBM is not sufficiently osteoinductive. Bone marrow has been known to magnify osteoinductive components for bone reconstruction because it contains osteogenic cells and factors. Mesenchymal stem cells (MSCs) derived from bone marrow are the gold standard for cell seeding in tissue-engineered biomaterials for bone repair, and these cells have demonstrated beneficial effects. However, the associated high cost and the complicated procedures limit the use of tissue-engineered bone constructs. To easily enrich more osteogenic cells and factors to DBM by selective cell retention technology, DBM is modified by a nanoscale self-assembling peptide (SAP) to form a composite DBM/SAP scaffold. By decreasing the pore size and increasing the charge interaction, DBM/SAP scaffolds possess a much higher enriching yield for osteogenic cells and factors compared with DBM alone scaffolds. At the same time, SAP can build a cellular microenvironment for cell adhesion, proliferation, and differentiation that promotes bone reconstruction. As a result, a suitable bone graft fabricated by DBM/SAP scaffolds and bone marrow represents a new strategy and product for bone transplantation in the clinic.

  10. Use of demineralized bone matrix in spinal fusion

    PubMed Central

    Tilkeridis, Konstantinos; Touzopoulos, Panagiotis; Ververidis, Athanasios; Christodoulou, Sotirios; Kazakos, Konstantinos; Drosos, Georgios I

    2014-01-01

    Spinal fusion remains the gold-standard treatment for several pathological spine conditions. Although, autologous Iliac Crest Bone Grafting is considered the gold-standard graft choice to promote spinal fusion; however, it is associated with significant donor site morbidity and a limited graft quantity. Therefore, several bone graft alternatives have been developed, to augment arthrodesis. The purpose of this review is to present the results of clinical studies concerning the use of demineralized bone matrix (DBM), alone or as a composite graft, in the spinal fusion. A critical review of the English-language literature was conducted on Pubmed, using key word “demineralized bone matrix”, “DBM”, “spinal fusion”, and “scoliosis”. Results had been restricted to clinical studies. The majority of clinical trials demonstrate satisfactory fusion rates when DBM is employed as a graft extender or a graft enhancer. Limited number of prospective randomized controlled trials (4 studies), have been performed comparing DBM to autologous iliac crest bone graft in spine fusion. The majority of the clinical trials demonstrate comparable efficacy of DBM when it used as a graft extender in combination with autograft, but there is no clinical evidence to support its use as a standalone graft material. Additionally, high level of evidence studies are required, in order to optimize and clarify the indications of its use and the appropriate patient population that will benefit from DBM in spine arthrodesis. PMID:24649412

  11. Osteogenetic activity in composite grafts of demineralized compact bone and marrow

    SciTech Connect

    Wittbjer, J.; Palmer, B.; Rohlin, M.; Thorngren, K.G.

    1983-03-01

    The effects of a composite graft of autologous marrow and demineralized autologous compact bone on the healing of a surgically created bone defect were observed in adult rabbits. A segment of the radius was bilaterally resected, demineralized, and replaced. On one side the bone graft was supplemented with autologous marrow. The new bone formation was measured 14 and 28 days after operation by roentgenography, including planimetry with scintigraphy and autoradiography using /sup 99m/Tc-labelled MDP. The composite graft, i.e., demineralized compact bone and marrow, had a significantly higher (p less than 0.01) bone formation rate 14 days after operation compared with the graft with demineralized compact bone in the opposite radius. At 28 days, however, there were no differences between the sides. Viable autologous marrow cells and demineralized autologous compact bone graft accelerate the rate of osteogenesis, but only at the beginning of the healing process.

  12. Demineralized Bone and BMPs: Basic Science and Clinical Utility.

    PubMed

    Glowacki, Julie

    2015-12-01

    The clinical demand for bone void fillers led to the development of off-the-shelf banked bone and synthetic and biologic substitute materials to be used either alone or as bone graft volume extenders. Demineralized bone (DB) has a remarkable capacity to induce new bone formation even when implanted subcutaneously in experimental animals, a phenomenon termed "osteoinduction." DB products are now widely available through tissue bank procurement of bone from rigorously screened donors. When properly processed, DB products are useful in craniomaxillofacial, oral, hand, and orthopedic applications. The isolation of proteins believed to be responsible for the osteoinductive activity of DB, termed bone morphogenetic proteins (BMPs), led to the cloning of a family of genes and synthesis of recombinant human BMPs (rhBMPs). They have been approved for distribution and use in specific maxillofacial and orthopedic applications. Clinical trials and studies of orthopedic and craniofacial applications have indicated that supraphysiologic doses of a single recombinant protein are needed to promote bone repair. Information about the biology, chemistry, and actions of rhBMPs and DB has called into question whether a single recombinant BMP would result in clinically useful bone induction and morphogenesis. Compelling preclinical and specific clinical evidence has indicated the efficacy of DB and for rhBMPs either combined with autograft or compared with an autograft alone. In light of questions about potency and safety, however, additional high-level evidence is needed for specific clinical indications and appropriate patient populations that would benefit from their use. PMID:26608140

  13. Hydrogels derived from demineralized and decellularized bone extracellular matrix

    PubMed Central

    Sawkins, M.J.; Bowen, W.; Dhadda, P.; Markides, H.; Sidney, L.E.; Taylor, A.J.; Rose, F.R.A.J.; Badylak, S.F.; Shakesheff, K.M.; White, L.J.

    2013-01-01

    The extracellular matrix (ECM) of mammalian tissues has been isolated, decellularized and utilized as a scaffold to facilitate the repair and reconstruction of numerous tissues. Recent studies have suggested that superior function and complex tissue formation occurred when ECM scaffolds were derived from site-specific homologous tissues compared with heterologous tissues. The objectives of the present study were to apply a stringent decellularization process to demineralized bone matrix (DBM), prepared from bovine bone, and to characterize the structure and composition of the resulting ECM materials and DBM itself. Additionally, we sought to produce a soluble form of DBM and ECM which could be induced to form a hydrogel. Current clinical delivery of DBM particles for treatment of bone defects requires incorporation of the particles within a carrier liquid. Differences in osteogenic activity, inflammation and nephrotoxicity have been reported with various carrier liquids. The use of hydrogel forms of DBM or ECM may reduce the need for carrier liquids. DBM and ECM hydrogels exhibited sigmoidal gelation kinetics consistent with a nucleation and growth mechanism, with ECM hydrogels characterized by lower storage moduli than the DBM hydrogels. Enhanced proliferation of mouse primary calvarial cells was achieved on ECM hydrogels, compared with collagen type I and DBM hydrogels. These results show that DBM and ECM hydrogels have distinct structural, mechanical and biological properties and have the potential for clinical delivery without the need for carrier liquids. PMID:23624219

  14. Functional hyposplenism following allogeneic bone marrow transplantation.

    PubMed Central

    Cuthbert, R J; Iqbal, A; Gates, A; Toghill, P J; Russell, N H

    1995-01-01

    AIMS--To investigate the incidence of functional hyposplenism in a group of patients who had undergone allogeneic bone marrow transplantation (BMT). METHODS--Splenic function was assessed by counting the number of gluteraldehyde fixed red blood cells containing pits or indentations as examined by interference phase microscopy. Normal values are < 2% whereas splenectomy patients have values of 25 to 40%. RESULTS--Twenty eight BMT recipients (17 men, 11 women) were studied at varying periods post-transplant and the results compared with 20 healthy volunteers and 10 patients who had undergone splenectomy or had splenic atrophy because of haematological conditions. Of the 28 BMT recipients, one had undergone a prior splenectomy; of the remaining 27 patients, four (15%) had evidence of functional hyposplenism with between 5.0 and 34.0% pitted cells. Of these four patients, one had active extensive chronic graft versus host disease (GvHD) which has been previously reported to be associated with functional hyposplenism following transplantation. Only one of the four patients had peripheral blood red cell changes typical of hyposplenism. CONCLUSION--These results confirm that extensive chronic GvHD is associated with hyposplenism. Intermediate degrees of functional hyposplenism may also occur following BMT in the absence of chronic GvHD and in the absence of haematological features of hyposplenism on routine blood films. This may be of significance in mediating the susceptibility to infection with encapsulating bacteria seen following allogeneic BMT. PMID:7730489

  15. [The influence of mesenchymal stem cells on bone tissue regeneration upon implantation of demineralized bone matrix].

    PubMed

    Krugliakov, P V; Sokolova, I B; Zin'kova, N N; Viĭde, S V; Cherednichenko, N N; Kisliakova, T V; Polyntsev, D G

    2005-01-01

    Mesenchymal stem cells (MSC) are resident pluripotent cells of bone marrow stroma. MSC are able to differentiate into chondroblasts, adipocytes, neurons, glia, cardiomyocytes, or osteoblasts. The problem of MSC usage in cell therapy of bone defects is widely discussed at present. The experiments were carried out using rats of inbred line Wistar-Kyoto. MSC were isolated from bone marrow and cultivated in vitro. Demineralized bone matrices (DBM) were obtained from parietal bones of rats and hens. Part of DBM was loaded with MSC. Bone defects were made in cranium parietal regions. DBM with or without MSC or metal plates were transplanted in these regions. It was shown that the application of MSC increased angiogenesis and osteogenesis in the damaged bone. The implantation of rat's DBM with MSC led to the formation of a full value bone. MSC suppressed inflammation, when transplantation of hen's DBM was carried out. The application of MSC always improved bone tissue regeneration.

  16. Optimized demineralization of human cancellous bone by application of a vacuum.

    PubMed

    Eagle, Mark J; Rooney, Paul; Kearney, John N

    2015-07-01

    Human demineralized bone matrix derived from cortical bone is used by surgeons due to its ability to promote bone formation. There is also a need for shaped demineralized bone matrices made from cancellous bone, where the properties of the material allow its insertion into defects, therefore acting as a void filler and scaffold onto which new bone can form. In this study, we report that demineralized bone sponges were prepared by dissecting and cutting knee bone into cancellous bone cubes of 1 cm(3) . These cubes were then taken through a series of warm water washes, some with sonication, centrifugation, and two decontamination chemical washes. The cubes were optimally demineralized into sponges with 0.5N hydrochloric acid under vacuum with constant pH measurement. Demineralization was confirmed by quantitative measurement of calcium and qualitatively by compression. The sponges were freeze dried before terminal sterilisation with a target dose of 25 kGy gamma radiation whilst frozen. Samples of the sponges were histologically examined for calcium and collagen and also tested for osteoinductivity. Data showed well defined collagen staining in the sponges, with little residual calcium. Sponges from two out of three donors demonstrated osteoinductivity when implanted into the muscle of an athymic mouse.

  17. Detailed Analysis of the Structural Changes of Bone Matrix During the Demineralization Process Using Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Timchenko, E. V.; Zherdeva, L. A.; Timchenko, P. E.; Volova, L. T.; Ponomareva, U. V.

    The results of experimental research of human cortical bone tissue depending on demineralization time were represented using Raman spectroscopy. Depending on demineralization time the ratio of the mineral (РO43- and CO32-) and organic components (amide I) of bone tissue, as well as changes in the spectral regions responsible for the structural integrity of the collagen fibers in bone tissue (1200-1460 cm-1 and 2880-3000 cm-1) were investigated. The observed changes show a decrease in mineral components: thus, the value of Raman band intensity at 956 and 1069 cm-1 for 5 minutes demineralization is 68.5 and 77.3%, for 20 minutes - 55.1 and 61.1%, for 120 minutes - 32.8 and 37% from Raman intensity values of not demineralized tissue objects respectively.

  18. 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.

  19. Enhanced release of bone morphogenetic proteins from demineralized bone matrix by gamma irradiation

    NASA Astrophysics Data System (ADS)

    Sung, Nak-Yun; Choi, Jong-il

    2015-06-01

    Gamma irradiation is a useful method for sterilizing demineralized bone matrix (DBM), but its effect on the osteoinductivity of DBM is still controversial. In this study, the osteoinductive activity of gamma-irradiated DBM was examined using a mouse myoblastic cell line (C2C12). DBM was extracted from adult bovine bone and was irradiated at a dose of 25 kGy using a 60cobalt gamma-irradiator. Cell proliferation with DBM was not affected by gamma-irradiation, but alkaline phosphatase and osteocalcin productions were significantly increased in C2C12 cell groups treated with gamma-irradiated DBM. It was reasoned that bone morphogenetic proteins were more efficiently released from gamma-irradiated DBM than from the non-irradiated control. This result suggests the effectiveness of radiation sterilization of bone implants

  20. Allogeneic and autologous bone marrow transplantation for acute nonlymphocytic leukemia.

    PubMed

    Hurd, D D

    1987-12-01

    Current results show that 50% of young patients with ANLL who undergo allogeneic BMT experience prolonged DFS and may be cured. Encouraging results with high-dose chemo/radiotherapy and autologous BMT are likewise being reported. In addition, some studies using intensive postremission treatment without BMT have shown results comparable to many transplant series. As better ways of preventing GVHD are found, the morbidity and mortality of allogeneic BMT should be reduced and the benefits of transplantation for curing patients with ANLL should be increased. However, the applicability of allogeneic BMT will remain limited due to the availability of compatible donors whether related or unrelated. Further studies are needed in the use of postremission intensive therapy with and without autologous bone marrow support. However, results to date should engender the same degree of enthusiastic optimism that followed the early reports of improved outcome with allogeneic BMT when applied to first remission patients. PMID:3321445

  1. Synthetic biodegradable hydrogel delivery of demineralized bone matrix for bone augmentation in a rat model

    PubMed Central

    Kinard, Lucas A.; Dahlin, Rebecca L.; Lam, Johnny; Lu, Steven; Lee, Esther J.; Kasper, F. Kurtis; Mikos, Antonios G.

    2014-01-01

    There exists a strong clinical need for a more capable and robust method to achieve bone augmentation, and a system with fine-tuned delivery of demineralized bone matrix (DBM) has potential to meet that need. As such, the objective of the present study was to investigate a synthetic biodegradable hydrogel for the delivery of DBM for bone augmentation in a rat model. Oligo(poly(ethylene glycol) fumarate) (OPF) constructs were designed and fabricated by varying the content of rat-derived DBM particles (either 1:3, 1:1, or 3:1 DBM:OPF weight ratio on a dry basis) and using two DBM particle size ranges (50–150 or 150–250 μm). The physical properties of the constructs and the bioactivity of the DBM were evaluated. Select formulations (1:1 and 3:1 with 50–150 μm DBM) were evaluated in vivo compared to an empty control to investigate the effect of DBM dose and construct properties on bone augmentation. Overall, 3:1 constructs with higher DBM content achieved the greatest volume of bone augmentation exceeding 1:1 constructs and empty implants by 3-fold and 5-fold, respectively. As such, we have established that a synthetic, biodegradable hydrogel can function as a carrier for DBM, and that the volume of bone augmentation achieved by the constructs correlated directly to DBM dose. PMID:25046637

  2. [T lymphocyte receptors after allogenic bone marrow transplantation].

    PubMed

    Vilmer, E; Schumpp, M; Sigaux, F; Boiron, M; Bensussan, A

    1988-01-01

    Following allogeneic bone marrow transplantation, prominent expansion of peripheral T cells (40%) bearing gamma T cell receptor was observed in some patients. Biochemical, functional and molecular analyses were performed to characterize this T cell receptor and to understand its role in the immunodeficient state after transplantation.

  3. Accelerated bone turnover identifies hemiplegic patients at higher risk of demineralization.

    PubMed

    Del Puente, A; Pappone, N; Servodio Iammarrone, C; Esposito, A; Scarpa, R; Costa, L; Caso, F; Bardoscia, A; Del Puente, A

    2016-01-01

    Immobilization osteoporosis represents a severe complication in hemiplegic patients (HPs), causing fragility fractures, which may occur during rehabilitation reducing functional recovery and survival. The aim of the study was to investigate determinants of bone loss, independent from length of immobilization, which may be useful in early identification of HPs at higher risk of demineralization. Forty-eight HPs of both sexes underwent anthropometric measurements, evaluation of scores of spasticity and of lower limb motory capacity. Laboratory tests were performed. On serum: calcium; phosphorus; creatinine; ALP; iPTH; 25(OH) vitamin-D; sex hormones; Δ4-androstenedione; DHEA-S; insulin; IGF-1; FT3; FT4; TSH; c-AMP. On urine: c-AMP and calcium/creatinine ratio. Two bone turnover markers were measured: serum osteocalcin (BGP) and urinary deoxypyridinoline (DPD). Bone mineral density was determined at both femoral necks, defining a percentage difference in bone loss between paretic and non-paretic limb, thus controlling for the complex cofactors involved. Only bone turnover markers significantly and directly correlated with the entity of demineralization, controlling for age, sex and length of immobilization in the multivariate analysis (BGP coefficient estimate=0.008; SE=0.003; p=0.020; DPD coefficient estimate=0.005; SE=0.002; p=0.036). BGP and DPD are not dependent on anthropometric and endocrine-metabolic parameters, disability patterns and duration of immobilization, thus represent independent determinants of the degree of demineralization. A cutoff was defined for BGP and DPD above which subjects show significantly greater risk of demineralization. The immobilization event generates more severe bone loss when it occurs in subjects with higher bone turnover. BGP and DPD measurements may be of primary importance for early identification of HPs at risk, with relevant preventive implications. PMID:27049105

  4. Accelerated bone turnover identifies hemiplegic patients at higher risk of demineralization.

    PubMed

    Del Puente, A; Pappone, N; Servodio Iammarrone, C; Esposito, A; Scarpa, R; Costa, L; Caso, F; Bardoscia, A; Del Puente, A

    2016-01-01

    Immobilization osteoporosis represents a severe complication in hemiplegic patients (HPs), causing fragility fractures, which may occur during rehabilitation reducing functional recovery and survival. The aim of the study was to investigate determinants of bone loss, independent from length of immobilization, which may be useful in early identification of HPs at higher risk of demineralization. Forty-eight HPs of both sexes underwent anthropometric measurements, evaluation of scores of spasticity and of lower limb motory capacity. Laboratory tests were performed. On serum: calcium; phosphorus; creatinine; ALP; iPTH; 25(OH) vitamin-D; sex hormones; Δ4-androstenedione; DHEA-S; insulin; IGF-1; FT3; FT4; TSH; c-AMP. On urine: c-AMP and calcium/creatinine ratio. Two bone turnover markers were measured: serum osteocalcin (BGP) and urinary deoxypyridinoline (DPD). Bone mineral density was determined at both femoral necks, defining a percentage difference in bone loss between paretic and non-paretic limb, thus controlling for the complex cofactors involved. Only bone turnover markers significantly and directly correlated with the entity of demineralization, controlling for age, sex and length of immobilization in the multivariate analysis (BGP coefficient estimate=0.008; SE=0.003; p=0.020; DPD coefficient estimate=0.005; SE=0.002; p=0.036). BGP and DPD are not dependent on anthropometric and endocrine-metabolic parameters, disability patterns and duration of immobilization, thus represent independent determinants of the degree of demineralization. A cutoff was defined for BGP and DPD above which subjects show significantly greater risk of demineralization. The immobilization event generates more severe bone loss when it occurs in subjects with higher bone turnover. BGP and DPD measurements may be of primary importance for early identification of HPs at risk, with relevant preventive implications.

  5. Pancytopenia after allogeneic bone marrow transplant due to copper deficiency.

    PubMed

    Hudspeth, Michelle; Turner, Amy; Miller, Nicole; Lazarchick, John

    2014-05-01

    Pancytopenia occurring 1 year or later after allogeneic bone marrow transplantation typically prompts a primary consideration for relapse. We present the case of a 15-year old-girl who underwent transplantation for therapy-related myelodysplasia secondary to Ewing sarcoma treatment who developed pancytopenia with myelodysplasia 1 year after transplant due to copper deficiency. Copper deficiency is an important consideration in the evaluation of pancytopenia and myelodysplasia in pediatric patients.

  6. Properties of the "Orgamax" osteoplastic material made of a demineralized allograft bone

    NASA Astrophysics Data System (ADS)

    Podorognaya, V. T.; Kirilova, I. A.; Sharkeev, Yu. P.; Uvarkin, P. V.; Zhelezny, P. A.; Zheleznaya, A. P.; Akimova, S. E.; Novoselov, V. P.; Tupikova, L. N.

    2016-08-01

    We investigated properties of the "Orgamax" osteoplastic material, which was produced from a demineralized bone, in the treatment of extensive caries, in particular chronic pulpitis of the permanent teeth with unformed roots in children. The "Orgamax" osteoplastic material consists of demineralized bone chips, a collagen additive, and antibiotics. The surface morphology of the "Orgamax" osteoplastic material is macroporous, with the maximum pore size of 250 µm, whereas the surface morphology of the major component of "Orgamax", demineralized bone chips, is microporous, with a pore size of 10-20 µm. Material "Orgamax" is used in the treatment of complicated caries, particularly chronic pulpitis of permanent teeth with unformed roots in children. "Orgamax" filling a formed cavity exhibits antimicrobial properties, eliminates inflammation in the dental pulp, and, due to its osteoconductive and osteoinductive properties, undergoes gradual resorption, stimulates regeneration, and provides replacement of the defect with newly formed tissue. The dental pulp viability is completely restored, which ensures the complete formation of tooth roots with root apex closure in the long-term period.

  7. Remineralization of Demineralized Bone Matrix (DBM) via Alternating Solution Immersion (ASI)

    PubMed Central

    Soicher, Matthew A.; Christiansen, Blaine A.; Stover, Susan M.; Leach, J. Kent; Fyhrie, David P.

    2013-01-01

    In order to achieve successful clinical outcomes, biomaterials used for bone grafts must possess a number of traits including biocompatibility and osteoconductivity. These materials must also demonstrate appropriate mechanical stability to withstand handling as well as support potentially significant stresses at the implant site. Synthetic and natural polymer scaffolds used for bone tissue engineering (BTE) often lack necessary mechanical properties. Our goal was to internally mineralize natural collagenous matrix, thereby increasing mechanical properties of the material to useful levels. Published methods for intrafibrillar collagen mineralization were applied to clinically relevant-sized constructs but did not successfully deposit mineral in the interior of the constructs. To address this limitation, we developed a new technique for the remineralization of demineralized bone matrix (DBM) based on alternating solution immersion, or ASI. Mineral was removed from equine bone specimens, leaving behind a demineralized bone matrix (DBM). This matrix provides a framework for the nucleation and growth of a replacement mineral phase. Plain film radiography and microcomputed tomography (microCT) indicated accumulation of mineral within the DBM, and mechanical testing (3 point bending and compression) revealed a significant increase in stiffness between the DBM and the remineralized bone matrix (RBM). We believe this remineralization process will be useful in the preparation of stiff and strong allografts for clinical application. PMID:23759125

  8. Allogeneic and Autologous Bone-Marrow Transplantation

    PubMed Central

    Deeg, H. Joachim

    1988-01-01

    The author of this paper presents an overview of the current status of bone marrow transplantation, including indications, pre-transplant considerations, the transplant procedure, acute and delayed transplant-related problems, results currently attainable, and a short discussion of possible future developments. PMID:21253121

  9. Postraumatic frontal sinus obliteration with calvarial bone dust and demineralized bone matrix: a long term prospective study and literature review.

    PubMed

    Rodríguez, I Z; Uceda, M I F; Lobato, R D; Aniceto, G S

    2013-01-01

    Defining the ideal material for frontal sinus obliteration remains controversial. Autogenous cancellous bone is effective because of its biological properties: it undergoes fast revascularization acting as an active scaffold for bone healing, but is linked to additional donor site morbidity. Bone dust harvesting from the skull surface produces no sequelae but availability is limited. Many efforts have been made to overcome these drawbacks, and an ideal bone substitute sought. Demineralized Bone Matrix (DBX; Musculoskeletal Transplant Foundation, Edison, NJ, USA) is a commercially available product composed of demineralized bone particles reduced after proper processing of human bone in combination with sodium hyaluronate. It generates an osteoconductive surface and it is also a source of osteoinductive factors. Radiological follow-up using computed tomography is a very reliable method of following-up ossification and detecting the early signs of possible complications. The authors present their clinical series of postraumatic frontal sinus obliteration using a mixture of calvarial bone dust and DBX shell, with long-term radiological monitoring. The technique was demonstrated to be effective, reliable, stable in the long term and associated with minimal morbidity.

  10. Fibular Allograft and Demineralized Bone Matrix for the Treatment of Slipped Capital Femoral Epiphysis.

    PubMed

    Murray, Travis; Morscher, Melanie A; Krahe, Amy M; Adamczyk, Mark J; Weiner, Dennis S

    2016-05-01

    Previous studies documented the use of fibular allograft in the treatment of slipped capital femoral epiphysis (SCFE) with bone graft epiphysiodesis (BGE). This study describes the results of using a 10-mm diameter premilled fibular allograft packed with demineralized bone matrix placed across the physis in an open surgical approach under image intensification. A review identified 45 cases of BGE using fibular allograft and demineralized bone matrix in 34 patients with a diagnosis of SCFE performed by a single surgeon during an 8-year period. Thirty-four cases (25 patients) had at least 1 year of follow-up and were included in the study. Medical records were reviewed for complications, subsequent surgeries, and time to physeal closure. Of the 34 cases included, there were no cases of acute chondrolysis. Complications included 1 case of bone graft extrusion that required surgical replacement and 1 re-slip requiring surgical stabilization. Five cases of avascular necrosis (AVN) were encountered (1 unstable slip with total head AVN, and 4 stable slips with 3 total head and 1 partial head AVN). In 1 patient, small loose bony fragments were noted on postoperative radiographs that appeared outside of the articular surface of the hip and were asymptomatic. Two patients encountered wound healing issues that resolved with appropriate wound care. In light of the occurrence of AVN in stable cases, BGE with autogenous corticocancellous graft is preferable to BGE with autologous fibular graft for the treatment of SCFE. [Orthopedics. 2016; 39(3):e519-e525.].

  11. Investigation of hyperelastic models for nonlinear elastic behavior of demineralized and deproteinized bovine cortical femur bone.

    PubMed

    Hosseinzadeh, M; Ghoreishi, M; Narooei, K

    2016-06-01

    In this study, the hyperelastic models of demineralized and deproteinized bovine cortical femur bone were investigated and appropriate models were developed. Using uniaxial compression test data, the strain energy versus stretch was calculated and the appropriate hyperelastic strain energy functions were fitted on data in order to calculate the material parameters. To obtain the mechanical behavior in other loading conditions, the hyperelastic strain energy equations were investigated for pure shear and equi-biaxial tension loadings. The results showed the Mooney-Rivlin and Ogden models cannot predict the mechanical response of demineralized and deproteinized bovine cortical femur bone accurately, while the general exponential-exponential and general exponential-power law models have a good agreement with the experimental results. To investigate the sensitivity of the hyperelastic models, a variation of 10% in material parameters was performed and the results indicated an acceptable stability for the general exponential-exponential and general exponential-power law models. Finally, the uniaxial tension and compression of cortical femur bone were studied using the finite element method in VUMAT user subroutine of ABAQUS software and the computed stress-stretch curves were shown a good agreement with the experimental data. PMID:26953961

  12. Effects of ionizing radiation on proteins in lyophilized or frozen demineralized human bone

    PubMed Central

    Antebi, Uri; Mathor, Monica Beatriz; da Silva, André Ferreira; Guimarães, Rodrigo Pereira; Honda, Emerson Kiyoshi

    2016-01-01

    Objective The aim was to study the effects of application of ionizing radiation (gamma and electrons) as sterilizing agents at doses of 15 kGy, 25 kGy and 50 kGy, on lyophilized or frozen demineralized bone tissue for use in transplants. Methods Five human femoral diaphyses from different donors of musculoskeletal tissue were demineralized and preserved as lyophilized or frozen at −80 °C. The samples were divided into two groups: non-irradiated (control) and irradiated by means of gamma rays or an electron beam. The bone proteins were extracted and used to determine the concentrations of total protein and BMP 2 and 7. Results Decreases in total protein and BMP 2 and 7 concentrations were observed. The decreases in total protein concentrations, in comparison with the respective control groups, were significant in the lyophilized and frozen samples that were irradiated at a dose of 50 kGy of gamma radiation and electron beam, with reductions of more than 30%. Significant decreases in the levels of BMP 2 and 7 were also observed at higher doses and especially through use of the electron beam. Conclusion The reductions in the concentrations of total proteins and osteoinductive proteins (BMP 2 and 7) were related to the radiation dose, i.e. they increased with higher doses of ionizing radiation type and the type of bone preservation. The largest reductions in concentrations were observed in the bones irradiated by means of an electron beam and at a dose of 50 kGy. However, this type of radiation and this high dose are not usual practices for sterilization of bone tissue. PMID:27069893

  13. Demineralized dentin matrix combined with recombinant human bone morphogenetic protein-2 in rabbit calvarial defects

    PubMed Central

    2016-01-01

    Objectives The aim of this study was to compare the osteogenic effects of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) in rabbit calvarial defects with DDM and anorganic bovine bone (ABB) combined with rhBMP-2. Materials and Methods Four round defects with 8-mm diameters were created in each rabbit calvaria. Each defect was treated with one of the following: 1) DDM, 2) ABB/rhBMP-2, or 3) DDM/rhBMP-2. The rhBMP-2 was combined with DDM and ABB according to a stepwise dry and dip lyophilizing protocol. Histological and microcomputed tomography (µCT) analyses were performed to measure the amount of bone formation and bone volume after 2- and 8-week healing intervals. Results Upon histological observation at two weeks, the DDM and ABB/rhBMP-2 groups showed osteoconductive bone formation, while the DDM/rhBMP-2 group showed osteoconductive and osteoinductive bone formation. New bone formation was higher in DDM/rhBMP-2, DDM and ABB decreasing order. The amounts of bone formation were very similar at two weeks; however, at eight weeks, the DDM/rhBMP-2 group showed a two-fold greater amount of bone formation compared to the DDM and ABB/rhBMP-2 groups. The µCT analysis showed markedly increased bone volume in the DDM/rhBMP-2 group at eight weeks compared with that of the DDM group. Notably, there was a slight decrease in bone volume in the ABB/rhBMP-2 group at eight weeks. There were no significant differences among the DDM, ABB/rhBMP-2, and DDM/rhBMP-2 groups at two or eight weeks. Conclusion Within the limitations of this study, DDM appears to be a suitable carrier for rhBMP-2 in orthotopic sites. PMID:27162749

  14. Demineralized bone promotes chondrocyte or osteoblast differentiation of human marrow stromal cells cultured in collagen sponges.

    PubMed

    Zhou, Shuanhu; Yates, Karen E; Eid, Karim; Glowacki, Julie

    2005-01-01

    Demineralized bone implants have been used for many types of craniomaxillofacial, orthopedic, periodontal, and hand reconstruction procedures. In previous studies, we showed that demineralized bone powder (DBP) induces chondrogenesis of human dermal fibroblasts in a DBP/collagen sponge system that optimized interactions between particles of DBP and target cells in cell culture. In this study, we test the hypothesis that DBP promotes chondrogenesis or osteogenesis of human marrow stromal cells (hMSCs) in 3-D collagen sponge culture, depending upon the culture conditions. We first confirmed that hMSCs have chondrogenic potential when treated with TGF-beta, either in 2-D monolayer cultures or in 3-D porous collagen sponges. Second, we found that DBP markedly enhanced chondrogenesis in hMSCs in 3-D sponges, as assessed by metachromasia and expression of chondrocyte-specific genes AGGRECAN, COL II, and COL X. Human dermal fibroblasts (hDFs) were used to define mechanisms of chondroinduction because unlike hMSCs they have no inherent chondrogenic potential. In situ hybridization revealed that hDFs vicinal to DBPs express chondrocyte-specific genes AGGRECAN or COL II. Macroarray analysis showed that DBP activates TGF-beta/BMP signaling pathway genes in hDFs. Finally, DBP induced hMSCs to express the osteoblast phenotype when cultured with osteogenic supplements. These studies show how culture conditions can influence the differentiation pathway that human marrow stromal cells follow when stimulated by DBP. These results support the potential to engineer cartilage or bone in vitro by using human bone marrow stromal cells and DBP/collagen scaffolds. PMID:15735899

  15. Antitumor immunomodulatory activity of allogenic bone marrow cells on TiNi scaffold

    NASA Astrophysics Data System (ADS)

    Kokorev, O. V.; Hodorenko, V. N.; Cherdyntseva, N. V.; Gunther, V. E.

    2016-08-01

    The present study was undertaken to evaluate the feasibility of modulation of anti-tumor response by allogenic bone marrow cell transplantation into porous TiNi-based scaffold. Transplantation of bone marrow cells into porous TiNi-based scaffold leads to antitumor (35%) and antimetastatic (55%) effects. The lifetime of tumor-bearing animals and implanted allogenic bone marrow cells in incubator of TiNi increases up to 60%. The possible mechanisms of the effect of allogenic cells on tumor process are the stimulation of endogenous effectors of antitumor immunity.

  16. [Kinetic study of splenocytes after allogeneic murine bone marrow transplantation].

    PubMed

    Liu, Jing-Hua; Zhou, Fan; Dou, Li-Ping; Wang, Li-Li; Wang, Xin-Rong; Li, Li; Yu, Li

    2010-08-01

    The study was purposed to understand immunological reconstitution of peripheral immune organs after transplantation, through establishing allogeneic murine bone marrow transplantation model and detecting the kinetic change of splenocytes after transplantation. C57BL/6 mice were donors, BALB/c mice were recipients. Recipient mice were divided into irradiation group (R), irradiation plus inoculating bone marrow mononuclear cells (MNC) group (B), and irradiation plus inoculating bone marrow mononuclear cells and spleno-MNC group (S). After transplantation, the mice were examined daily for the symptoms such as weight, hunched posture, activity, ruffled fur, diarrhea, and survival. Blood routine test was done once a week, splenocyte was counted and CD3, CD4, CD8, B220, CD11c positive cell relative count was detected by FACS on day 2, 7, 14, 27, 60 after transplantation, Liver, skin and intestine were biopsied for histopathological examination before dying. The results indicated that 89% mice in S group died of acute graft-versus-host disease (aGVHD) during day 6 to 78. The spleno-mononuclear cell count quickly decreased and reached to lowest level on day 2, then gradually recovered to level of pretransplantation on day 14; CD8 and B220 positive cells decreased to lowest level on day 12, in which CD8(+) cells quickly recovered and reached to level of pretransplantation, but the B220(+) recovered most slowly and sustained to be with low level, then gradually recovered to level of pretransplantation on day 60; CD3 and CD4 positive cells decreased relatively slowly, and reached to lowest level on day 14, then both gradually recovered to level of pretransplantation on day 60; CD11c positive cell count changed unstrikingly except day 14. It is concluded that when C57BL/6 mice are donors, and BALB/c mice are recipients treated with irradiation of 7.5 Gy and inoculated with 1 x 10⁷ bone marrow MNC and 1 x 10⁷ spleno-MNC, allogeneic murine bone marrow transplantation model

  17. Reconstruction of coup de sabre deformity (linear localized scleroderma) by using galeal frontalis muscle flap and demineralized bone matrix combination.

    PubMed

    Cavusoglu, Tarik; Yazici, Ilker; Vargel, Ibrahim; Karakaya, Esen Ibrahim

    2011-01-01

    In this clinical report, we are presenting the combination of demineralized bone matrix combined with bilateral galea frontalis flaps. Based on our 6-month results, this seems to be a reasonable combination to accomplish long-lasting restoration of forehead defects related to en coup de sabre linear localized scleroderma.

  18. Allogeneic bone marrow transplantation for postpolycythemic myeloid metaplasia with myelofibrosis: a case report.

    PubMed

    de Revel, T; Giraudier, S; Nedellec, G; Joussemet, M; Bourin, P; Schill, H; Gaillard, J F; Auzanneau, G

    1995-07-01

    Myeloid metaplasia with myelofibrosis develops in about 10% of patients with polycythemia vera. We report a case of a 48-year-old female with postpolycythemic myelofibrosis successfully treated with allogeneic HLA-matched bone marrow transplantation.

  19. [Aplication of demineralized human bone matrix in the surgical dental fusion treatment. Report of a case].

    PubMed

    Mora-Rincones, Oscar A; Corona-Rodríguez, Julio C; Díaz-Carvajal, Alvaro L; Franco-Carrero, Isabel C

    2008-06-01

    The purpose of this work is to present a surgical alternative in the treatment of the dental fusions through the placement of demineralized human bone matrix (DHBM) (Grafton Putty)*, immediately after the separation and extraction of the fused tooth to the permanent one. The dental fusion is a dental anomaly of union, that consists in the union of two dental germs during development. It could happen at any of the dental germ evolution stages from the dental sheet or from more advanced processes of differentiation. For the clinical treatment, an allograft of DHBM with osteoinductive and osteoconductive properties was used. This had several factors of bone growth, it allowed the gradual growth of a new bone that helped to correct the bone defects post-extraction and to cover the exposed distal wall of the remaining permanent tooth. The clinic evaluation and the periapical and panoramic radiographies images were used for the clinical control. It can be concluded that the surgical separation and the extraction of the tooth with less anatomical likeness to the contralateral and the placement of the DHBM, represent a surgical treatment alternative of the dental fusion.

  20. Heterotopic Ossification around the Knee after Internal Fixation of a Complex Tibial Plateau Fracture Combined with the Use of Demineralized Bone Matrix (DBM): A Case Report

    PubMed Central

    Nota, Sjoerd P.F.T.; Kloen, Peter

    2014-01-01

    Demineralized bone matrix has been successfully commercialized as an alternative bone graft material that not only can function as filler but also as an osteoinductive graft. Numerous studies have confirmed its beneficial use in clinical practice. Heterotopic ossification after internal fixation combined with the use of demineralized bone matrix has not been widely reported. In this paper we describe a 39 year old male who sustained a complex articular fracture that developed clinically significant heterotopic ossification after internal fixation with added demineralized bone matrix. Although we cannot be sure that there is a cause-and-effect relation between demineralized bone matrix and the excessive heterotopic ossification seen in our patient, it seems that some caution in using demineralised bone matrix in similar cases is warranted. Also, given the known inter- and intraproduct variability, the risks and benefits of these products should be carefully weighed. PMID:25692153

  1. 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

  2. Combination of absorbable mesh and demineralized bone matrix in orbital wall fracture for preventing herniation of orbit.

    PubMed

    Tak, Kyoung Seok; Jung, Min Su; Lee, Byeong Ho; Kim, Joo Hyun; Ahn, Duk Kyun; Jeong, Hii Sun; Park, Young Kyu; Suh, In Suck

    2014-07-01

    After restoration of orbit wall fracture, preventing sequelae is important. An absorbable mesh is commonly used in orbit wall fracture, yet it has limitation due to orbit sagging when bony defect is larger than the moderate size (1 × 1 cm2). In this study, the authors present a satisfactory result in treating orbit wall fracture larger than the moderate size with a combination of absorbable mesh and demineralized bone matrix.From 2009 to 2012, 63 patients with bony defect larger than the moderate size, who were treated with a combination of absorbable mesh and demineralized bone matrix, were reviewed retrospectively. The site of bony defect, size, and applied amount of demineralized bone matrix were reviewed, and a 2-year follow-up was done. Facial computed tomography scans were checked preoperative, immediate postoperative, and 2-year postoperative.Among the 63 patients, there were 52 men and 11 women. Mean age was 33.3 years. The most common cause was blunt blow (35 cases); mean defect size was 13.36 × 12.82 mm2 in inferior wall fracture and 20.69 × 14.41 mm2 in medial wall fracture. There was no complication except for 3 cases of infraorbital nerve hypoesthesia. A 2-year follow-up computed tomography showed that the surgical site preserved bony formation without herniation. In treating moderate-sized bony defect in orbit wall fracture, absorbable mesh and demineralized bone matrix can maintain structural stability through good bony formation even after degradation of absorbable mesh.

  3. Comparison of autogenic and allogenic bone marrow derived mesenchymal stem cells for repair of segmental bone defects in rabbits.

    PubMed

    Udehiya, Rahul Kumar; Amarpal; Aithal, H P; Kinjavdekar, P; Pawde, A M; Singh, Rajendra; Taru Sharma, G

    2013-06-01

    Autogenic and allogenic bone marrow derived mesenchymal stem cells (BM-MSCs) were compared for repair of bone gap defect in rabbits. BM-MSCs were isolated from bone marrow aspirates and cultured in vitro for allogenic and autogenic transplantation. A 5mm segmental defect was created in mid-diaphysis of the radius bone. The defect was filled with hydroxyapatite alone, hydroxyapatite with autogeneic BM-MSCs and hydroxyapatite with allogenic BM-MSCs in groups A, B and C, respectively. On an average 3.45×10(6) cells were implanted at each defect site. Complete bridging of bone gap with newly formed bone was faster in both treatment groups as compared to control group. Histologically, increased osteogenesis, early and better reorganization of cancellous bone and more bone marrow formation were discernible in treatment groups as compared to control group. It was concluded that in vitro culture expanded allogenic and autogenic BM-MSCs induce similar, but faster and better healing as compared to control.

  4. Intentional replantation of periodontally hopeless teeth using a combination of enamel matrix derivative and demineralized freeze-dried bone allograft.

    PubMed

    Baltacioglu, Ersa; Tasdemir, Tamer; Yuva, Pinar; Celik, Davut; Sukuroglu, Erkan

    2011-02-01

    This study evaluated the clinical and radiographic results of the intentional replantation of periodontally hopeless teeth with combined enamel matrix derivative and demineralized freeze-dried bone allograft therapy. Eleven patients (five female, six male; age range, 13 to 53 years) with 12 periodontally hopeless teeth resulting from extensive alveolar bone loss and vertical defects extending to the apexes were studied. At the 12-month clinical and radiologic follow-up, significant improvement was observed for all clinical and radiographic parameters except gingival recession (P < .05). These preliminary findings show that intentional replantation combined with regenerative techniques is a successful alternative to tooth extraction.

  5. Remineralization of demineralized bone matrix in critical size cranial defects in rats: A 6-month follow-up study.

    PubMed

    Horváthy, Dénes B; Vácz, Gabriella; Toró, Ildikó; Szabó, Tamás; May, Zoltán; Duarte, Miguel; Hornyák, István; Szabó, Bence T; Dobó-Nagy, Csaba; Doros, Attila; Lacza, Zsombor

    2016-10-01

    The key drawback of using demineralized bone matrix (DBM) is its low initial mechanical stability due to the severe depletion of mineral content. In the present study, we investigated the long-term regeneration of DBM in a critical size bone defect model and investigated the remineralization after 6 months. Bone defects were created in the cranium of male Wistar rats which were filled with DBM or left empty as negative control. In vivo bone formation was monitored with computed tomography after 11, 19, and 26 weeks postoperatively. After 6 months, parietal bones were subjected to micro-CT. Mineral content was determined with spectrophotometric analysis. After 11 weeks the DBM-filled bone defects were completely closed, while empty defects were still open. Density of the DBM-treated group increased significantly while the controls remained unchanged. Quantitative analysis by micro-CT confirmed the in vivo results, bone volume/tissue volume was significantly lower in the controls than in the DBM group. The demineralization procedure depleted the key minerals of the bone to a very low level. Six months after implantation Ca, P, Na, Mg, Zn, and Cr contents were completely restored to the normal level, while K, Sr, and Mn were only partially restored. The remineralization process of DBM is largely complete by the 6th month after implantation in terms of bone density, structure, and key mineral levels. Although DBM does not provide sufficient sources for any of these minerals, it induces a faster and more complete regeneration process. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1336-1342, 2016.

  6. Cartilage tissue engineering of nasal septal chondrocyte-macroaggregates in human demineralized bone matrix.

    PubMed

    Liese, Juliane; Marzahn, Ulrike; El Sayed, Karym; Pruss, Axel; Haisch, Andreas; Stoelzel, Katharina

    2013-06-01

    Tissue Engineering is an important method for generating cartilage tissue with isolated autologous cells and the support of biomaterials. In contrast to various gel-like biomaterials, human demineralized bone matrix (DBM) guarantees some biomechanical stability for an application in biomechanically loaded regions. The present study combined for the first time the method of seeding chondrocyte-macroaggregates in DBM for the purpose of cartilage tissue engineering. After isolating human nasal chondrocytes and creating a three-dimensional macroaggregate arrangement, the DBM was cultivated in vitro with the macroaggregates. The interaction of the cells within the DBM was analyzed with respect to cell differentiation and the inhibitory effects of chondrocyte proliferation. In contrast to chondrocyte-macroaggregates in the cell-DBM constructs, morphologically modified cells expressing type I collagen dominated. The redifferentiation of chondrocytes, characterized by the expression of type II collagen, was only found in low amounts in the cell-DBM constructs. Furthermore, caspase 3, a marker for apoptosis, was detected in the chondrocyte-DBM constructs. In another experimental setting, the vitality of chondrocytes as related to culture time and the amount of DBM was analyzed with the BrdU assay. Higher amounts of DBM tended to result in significantly higher proliferation rates of the cells within the first 48 h. After 96 h, the vitality decreased in a dose-dependent fashion. In conclusion, this study provides the proof of concept of chondrocyte-macroaggregates with DBM as an interesting method for the tissue engineering of cartilage. The as-yet insufficient redifferentiation of the chondrocytes and the sporadic initiation of apoptosis will require further investigations.

  7. Mouse host unlicensed NK cells promote donor allogeneic bone marrow engraftment

    PubMed Central

    Alvarez, Maite; Sun, Kai

    2016-01-01

    Natural killer (NK) cells exist as subsets based on expression of inhibitory receptors that recognize major histocompatibility complex I (MHCI) molecules. NK cell subsets bearing MHCI binding receptors for self-MHCI have been termed as “licensed” and exhibit a higher ability to respond to stimuli. In the context of bone marrow transplantation (BMT), host licensed-NK (L-NK) cells have also been demonstrated to be responsible for the acute rejection of allogeneic and MHCI-deficient BM cells (BMCs) in mice after lethal irradiation. However, the role of recipient unlicensed-NK (U-NK) cells has not been well established with regard to allogeneic BMC resistance. After NK cell stimulation, the prior depletion of host L-NK cells resulted in a marked increase of donor engraftment compared with the untreated group. Surprisingly, this increased donor engraftment was reduced after total host NK cell depletion, indicating that U-NK cells can actually promote donor allogeneic BMC engraftment. Furthermore, direct coculture of U-NK cells with allogeneic but not syngeneic BMCs resulted in increased colony-forming unit cell growth in vitro, which was at least partially mediated by granulocyte macrophage colony-stimulating factor (GM-CSF) production. These data demonstrate that host NK cell subsets exert markedly different roles in allogeneic BMC engraftment where host L- and U-NK cells reject or promote donor allogeneic BMC engraftment, respectively. PMID:26738538

  8. Matched Comparison of Fusion Rates between Hydroxyapatite Demineralized Bone Matrix and Autograft in Lumbar Interbody Fusion

    PubMed Central

    Kim, Dae Hwan; Lee, Nam; Shin, Dong Ah; Yi, Seong; Kim, Keung Nyun

    2016-01-01

    Objective To compare the fusion rate of a hydroxyapatite demineralized bone matrix (DBM) with post-laminectomy acquired autograft in lumbar interbody fusion surgery and to evaluate the correlation between fusion rate and clinical outcome. Methods From January 2013 to April 2014, 98 patients underwent lumbar interbody fusion surgery with hydroxyapatite DBM (HA-DBM group) in our institute. Of those patients, 65 received complete CT scans for 12 months postoperatively in order to evaluate fusion status. For comparison with autograft, we selected another 65 patients who underwent lumbar interbody fusion surgery with post-laminectomy acquired autograft (Autograft group) during the same period. Both fusion material groups were matched in terms of age, sex, body mass index (BMI), and bone mineral density (BMD). To evaluate the clinical outcomes, we analyzed the results of visual analogue scale (VAS), Oswestry Disability Index (ODI), and Short Form Health Survey (SF-36). Results We reviewed the CT scans of 149 fusion levels in 130 patients (HA-DBM group, 75 levels/65 patients; Autograft group, 74 levels/65 patients). Age, sex, BMI, and BMD were not significantly different between the groups (p=0.528, p=0.848, p=0.527, and p=0.610, respectively). The HA-DBM group showed 39 of 75 fused levels (52%), and the Autograft group showed 46 of 74 fused levels (62.2%). This difference was not statistically significant (p=0.21). In the HA-DBM group, older age and low BMD were significantly associated with non-fusion (61.24 vs. 66.68, p=0.027; -1.63 vs. -2.29, p=0.015, respectively). VAS and ODI showed significant improvement after surgery when fusion was successfully achieved in both groups (p=0.004, p=0.002, HA-DBM group; p=0.012, p=0.03, Autograft group). Conclusion The fusion rates of the hydroxyapatite DBM and Autograft groups were not significantly different. In addition, clinical outcomes were similar between the groups. However, older age and low BMD are risk factors that might

  9. Medial femoral condyle fracture following traumatic allogenic bone transfer – A case report

    PubMed Central

    Kondreddi, Vamsi; Roy, Kishore; Yalamanchili, Ranjith Kumar

    2015-01-01

    Open fractures can cause an “out-in” injury, wherein a foreign body can penetrate the skin causing fracture. There are few reports of allogenic bone getting embedded in soft tissue, but one causing fracture to the host bone has not been reported till date. We present a case, wherein a large cortical bony fragment from one individual penetrated the thigh of another person causing fracture of medial femoral condyle during a head-on collision involving two motorbikes. PMID:26155058

  10. Investigation of allogeneic mesenchymal stem cell-based alveolar bone formation: preliminary findings.

    PubMed

    De Kok, Ingeborg J; Peter, Susan J; Archambault, Michael; van den Bos, Christian; Kadiyala, Sudha; Aukhil, Ikramuddin; Cooper, Lyndon F

    2003-08-01

    This study was designed to evaluate mesenchymal stem cell (MSC)-based alveolar bone regeneration in a canine alveolar saddle defect model. MSCs were loaded onto hydroxyapatite/tricalcium phosphate (HA/TCP) matrices. Scanning electron microscopic (SEM) evaluation demonstrated greater than 75% MSC coverage of the HA/TCP porous surface prior to placement regardless of MSC donor. Matrices, 6 mm x 6 mm x 20 mm, with and without cells, were implanted for 4 and 9 weeks, then removed for histological evaluation of bone formation. Cell-free control matrices were compared with MSC-loaded matrices post implantation. Histomorphometrical analysis showed that equivalent amounts of new bone were formed within the pores of the matrices loaded with autologous MSCs or MSCs from an unrelated donor. Bone formation in the cell-free HA/TCP matrices was less extensive. There was no histologic evidence of an immunological response to autologous MSCs. Surprisingly, allogeneic MSC implantation also failed to provoke an immune response. Analysis of circulating antibody levels against MSCs supported the hypothesis that neither autologous nor allogeneic MSCs induced a systemic response by the host. Analysis of dye-labelled MSCs in histological sections confirmed that the MSCs persisted in the implants throughout the course of the experiment. At 9 weeks, labelled cells were present within the lacunae of newly formed bone. We conclude that autologous and allogeneic MSCs have the capacity to regenerate bone within craniofacial defects.

  11. Early establishment of hematopoietic chimerism following allogeneic peripheral blood stem cell transplantation in comparison with allogeneic bone marrow transplantation.

    PubMed

    Nakao, S; Zeng, W; Yamazaki, H; Wang, H; Takami, A; Sugimori, N; Miura, Y; Shiobara, S; Matsuda, T; Shinagawa, Y; Harada, M

    1999-04-01

    To characterize the process of the establishment of complete chimerism after allogeneic peripheral blood stem cell transplantation (allo-PBSCT), we determined the origin of leukocytes in peripheral blood (PB) obtained from 23 patients in the very early period after allo-PBSCT using amplification of mini- or microsatellite regions of genomic DNA. Donor-specific alleles were amplified from the PB obtained at day 8 post-transplant for 19 allo-PBSCT patients. Among the 19 patients, 12 showed only donor-specific alleles (complete chimerism) while 7 did both donor and host-specific alleles (mixed chimerism). Although donor specific alleles were amplified in 10 of 12 patients who received allogeneic bone marrow transplantation (allo-BMT) similarly to allo-PBSCT, all of these ten showed mixed chimerism. When the chimeric state was examined in PB samples obtained serially at 2-3-day intervals post-transplant, host-specific alleles in allo-PBSCT patients were not detectable in the PB much earlier than those in allo-BMT patients. These findings indicate that the appearance of donor-derived cells associated with the disappearance of host-derived cells in the circulation occurs earlier after allo-PBSCT as compared with allo-BMT, leading to the rapid establishment of complete chimerism.

  12. Systemic Administration of Allogeneic Mesenchymal Stem Cells Does Not Halt Osteoporotic Bone Loss in Ovariectomized Rats

    PubMed Central

    Sun, Yuxin; Lin, Sien; Gu, Weidong; Liu, Yamei; Zhang, Jinfang; Chen, Lin; Li, Gang

    2016-01-01

    Mesenchymal stem cells (MSCs) have innate ability to self-renew and immunosuppressive functions, and differentiate into various cell types. They have become a promising cell source for treating many diseases, particular for bone regeneration. Osteoporosis is a common metabolic bone disorder with elevated systemic inflammation which in turn triggers enhanced bone loss. We hypothesize that systemic infusion of MSCs may suppress the elevated inflammation in the osteoporotic subjects and slow down bone loss. The current project was to address the following two questions: (1) Will a single dose systemic administration of allogenic MSCs have any effect on osteoporotic bone loss? (2) Will multiple administration of allogenic MSCs from single or multiple donors have similar effect on osteoporotic bone loss? 18 ovariectomized (OVX) rats were assigned into 3 groups: the PBS control group, MSCs group 1 (receiving 2x106 GFP-MSCs at Day 10, 46, 91 from the same donor following OVX) and MSCs group 2 (receiving 2x106 GFP-MSCs from three different donors at Day 10, 46, 91). Examinations included Micro-CT, serum analysis, mechanical testing, immunofluorescence staining and bone histomorphometry analysis. Results showed that BV/TV at Day 90, 135, BMD of TV and trabecular number at Day 135 in the PBS group were significantly higher than those in the MSCs group 2, whereas trabecular spacing at Day 90, 135 was significantly smaller than that in MSCs group 2. Mechanical testing data didn’t show significant difference among the three groups. In addition, the ELISA assay showed that level of Rantes in serum in MSCs group 2 was significantly higher than that of the PBS group, whereas IL-6 and IL-10 were significantly lower than those of the PBS group. Bone histomorphometry analysis showed that Oc.S/BS and Oc.N/BS in the PBS group were significant lower than those in MSCs group 2; Ob.S/BS and Ob.N/BS did not show significant difference among the three groups. The current study

  13. Transplantation tolerance in primates after total lymphoid irradiation and allogeneic bone marrow injection

    SciTech Connect

    Smit, J.A.; Hill, R.R.H.; Myburgh, J.A.; Browde, S.

    1980-08-01

    After total lymphoid irradiation (TLI), allogeneic bone marrow (BM) injection, and organ transplantation in baboons, there is a prolonged period of reduced lymphocyte proliferative responsiveness to polyclonal mitogens and allogeneic lymphocytes. The effect observed is greater with the use of fractionated TLI than after single doses of irradiation. Suppressor cell activity can be demonstrated in vitro in most animals by inhibition of mixed lymphocyte reactivity (MLR) by mitomycin-treated recipient lymphocytes harvested after TLI, with or without allogeneic BM injection, and organ transplantation. Preliminary data suggest the presence of both donor-specific and nondonor-specific suppression, although other interpretations are possible, and suppressor phenomena may not be responsible for the transplantation tolerance observed.

  14. Implant installation with bone augmentation and transmucosal healing with demineralized human cortical bone in the maxillary anterior region: report of 3 cases.

    PubMed

    Park, Jun-Beom

    2012-12-01

    It is well known that a decrease in vertical height and in horizontal width is seen after tooth extraction. Immediate implant placement, originally thought to prevent buccal wall resorption, showed little or no evident decrease of the resorption rate or pattern in animal experiments or clinical studies. Thus, the need for bone augmentation with immediate implantation has been suggested. However, until recently, simultaneous bone augmentation with immediate implant placement was thought to be possible only in a submerged environment. In this report, the harmony of soft and hard tissue was achieved in 3 patients by immediate implant placement and bone augmentation with transmucosal healing in esthetically challenging situations. Further evaluation is needed to monitor hard- and soft-tissue changes on a long-term basis. Implant placement and bone augmentation with transmucosal healing using demineralized bone matrix may be an option in the treatment of the loss of anterior teeth. PMID:21126168

  15. Rapid demineralization in acidic buffers.

    PubMed

    Eggert, F M; Germain, J P

    1979-01-22

    The demineralization of routine histological specimens in buffers of weakly ionized organic acids, unbuffered formic acid, and EDTA was investigated. The rate of demineralization was measured by a chemical method and from radiographs. Lactate-containing buffers and buffers of formic acid with its potassium salt were more rapid in effect than any other agent. Acidic buffers and unbuffered formic acid produced rapid diffuse demineralization with secondary precipitation of calcium salts. Preservation of dental enamel in such buffers resulted from the significantly slower rate of enamel demineralization than that for bone and dentine. In rapid demineralizing agents the secondary salts were quickly redissolved while in slow buffers these salts persisted. Multivalent ions such as citrate and maleate slowed the rate of demineralization, and a citrate-containing buffer was the slowest of all the agents tested. Demineralization in EDTA exhibited a different pattern with the establishment of a well-defined front of demineralization without apparent reprecipitation. EDTA attacked enamel, bone and dentine at the same rate. An attempt was made to relate the observed rates of demineralization to current theories of the demineralization process.

  16. Morganella morganii pericarditis 3 years after allogenic bone marrow transplantation for mantle cell lymphoma.

    PubMed

    Yang, Zhi-Tao; Lecuit, Marc; Suarez, Felipe; Carbonnelle, Etienne; Viard, Jean-Paul; Dupont, Bertrand; Buzyn, Agnès; Lortholary, Olivier

    2006-11-01

    We report herein a case of Morganella morganii-associated acute purulent pericarditis that developed 3 years after allogenic bone marrow transplantation. The patient was successfully treated with surgical drainage and cefotaxime for 6 weeks. Splenectomy and immunosuppression for chronic GVH-D are likely to have favored the development of this rare infectious complication after BMT. M. morganii should be added to the list of bacteria causing purulent pericarditis, especially in immunocompromised hosts.

  17. Elastic moduli of untreated, demineralized and deproteinized cortical bone: validation of a theoretical model of bone as an interpenetrating composite material.

    PubMed

    Hamed, E; Novitskaya, E; Li, J; Chen, P-Y; Jasiuk, I; McKittrick, J

    2012-03-01

    A theoretical experimentally based multi-scale model of the elastic response of cortical bone is presented. It portrays the hierarchical structure of bone as a composite with interpenetrating biopolymers (collagen and non-collagenous proteins) and minerals (hydroxyapatite), together with void spaces (porosity). The model involves a bottom-up approach and employs micromechanics and classical lamination theories of composite materials. Experiments on cortical bone samples from bovine femur include completely demineralized and deproteinized bones as well as untreated bone samples. Porosity and microstructure are characterized using optical and scanning electron microscopy, and micro-computed tomography. Compression testing is used to measure longitudinal and transverse elastic moduli of all three bone types. The characterization of structure and properties of these three bone states provides a deeper understanding of the contributions of the individual components of bone to its elastic response and allows fine tuning of modeling assumptions. Very good agreement is found between theoretical modeling and compression testing results, confirming the validity of the interpretation of bone as an interpenetrating composite material.

  18. Transforaminal lumbar interbody fusion rates in patients using a novel titanium implant and demineralized cancellous allograft bone sponge

    PubMed Central

    Girasole, Gerard; Muro, Gerard; Mintz, Abraham; Chertoff, Jason

    2013-01-01

    Background Transforaminal lumbar interbody fusion (TLIF) with grafting and implant options like iliac crest bone graft (ICBG), recombinant bone morphogenetic protein (rhBMP), and polyetheretherketone (PEEK) cages have been reported to achieve extremely high fusion rates. Unfortunately, these options have also been frequently cited in the literature as causing postoperative morbidity and complications at a high cost. Knowing this, we sought to investigate TLIF using an acid-etched, roughened titanium cage that upregulates osteogenesis to see if similar fusion rates to those cited for ICBG, rhBMP, and PEEK cages could be safely achieved with minimal morbidity and complications. Materials and methods A radiographic fusion study of 82 patients who underwent TLIF using an acid-etched, roughened titanium cage with demineralized cancellous bone graft was conducted. Fusion was assessed and graded by an independent radiologist using computed tomography scan with sagittal and coronal reconstructions. Results Fusion rates at 6 months were 41 of 44 (93.2%) and at 12 months were 37 of 38 (97.4%). There were no radiographic device-related complications. Conclusions TLIF with an acid-etched, roughened titanium cage filled with a decalcified bone graft achieved similar fusion rates to historical controls using ICBG, rhBMP, and PEEK. PMID:25580378

  19. 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.

  20. Immediate placement of a porous-tantalum, trabecular metal-enhanced titanium dental implant with demineralized bone matrix into a socket with deficient buccal bone: A clinical report

    PubMed Central

    Bencharit, Sompop; Byrd, Warren C.; Hosseini, Bashir

    2014-01-01

    A missing or deficient buccal alveolar bone plate is often an important limiting factor for immediate implant placement. Titanium dental implants enhanced with porous, tantalum-based trabecular metal material (PTTM) are designed for osseoincorporation, a combination of vascularized bone ingrowth and osseointegration (bone on-growth). Demineralized bone matrix (DBM) contains growth factors with good handling characteristics. However, the combination of these 2 materials in facial alveolar bone regeneration associated with immediate implant therapy has not been reported. A 65-year-old Asian woman presented with a failing central incisor. Most of the buccal alveolar bone plate of the socket was missing. A PTTM enhanced implant was immediately placed with DBM. Cone beam CT scans 12 months after the insertion of the definitive restoration showed regeneration of buccal alveolar bone. A combination of a PTTM enhanced implant, DBM, and a custom healing abutment may have an advantage in retaining biologically active molecules and form a scaffold for neovascularization and osteogenesis. This treatment protocol may be a viable option for immediate implant therapy in a failed tooth with deficient buccal alveolar bone. PMID:25702965

  1. Augmentation of intramembranous bone in rabbit calvaria using an occlusive barrier in combination with demineralized bone matrix (DBM): a pilot study.

    PubMed

    Beltrán, Víctor; Engelke, Wilfried; Prieto, Ruth; Valdivia-Gandur, Iván; Navarro, Pablo; Manzanares, María Cristina; Borie, Eduardo; Fuentes, Ramón

    2014-01-01

    The aim of this study was to histologically evaluate the performance of demineralized bone matrix (DBM) when compared with a blood clot in addition to an occlusive barrier in the bone regeneration process for bone defects in a rabbit model. Prefabricated metallic capsules with 4.5 mm and 3.5 mm dimensions were placed in five adult rabbit skulls. At the right side, the capsule was filled with DBM, and the clot was located on the left side. The barriers were supplied with a 0.5 mm horizontal peripheral flap and a vertical edge, fitting tightly into a circular slit prepared by a trephine in the skull. After a healing period of three months, the animals were sacrificed, and the samples were prepared for histological and histomorphometric analyses after capsule removal. Trabecular and medullar bone percentages were calculated from the different areas of the newly formed bone inside the metallic barriers, and non-parametric statistical analysis was used to describe the findings. The results showed a complete filling of newly formed bone inside the capsules of both groups. Less mature bone tissue was observed in the upper third of all samples, and a higher trabecular area was observed in the samples with DBM. The use of barriers resulted in the augmentation of newly formed bone in a three-month period. However, a higher trabecular area was observed in the barriers filled with DBM.

  2. Immediate placement of a porous-tantalum, trabecular metal-enhanced titanium dental implant with demineralized bone matrix into a socket with deficient buccal bone: a clinical report.

    PubMed

    Bencharit, Sompop; Byrd, Warren C; Hosseini, Bashir

    2015-04-01

    A missing or deficient buccal alveolar bone plate is often an important limiting factor for immediate implant placement. Titanium dental implants enhanced with porous tantalum-based trabecular metal material (PTTM) are designed for osseoincorporation, a combination of vascularized bone ingrowth and osseointegration (bone on-growth). Demineralized bone matrix (DBM) contains growth factors with good handling characteristics. However, the combination of these 2 materials in facial alveolar bone regeneration associated with immediate implant therapy has not been reported. A 65-year-old Asian woman presented with a failing central incisor. Most of the buccal alveolar bone plate of the socket was missing. A PTTM enhanced implant was immediately placed with DBM. Cone beam computed tomography scans 12 months after the insertion of the definitive restoration showed regeneration of buccal alveolar bone. A combination of a PTTM enhanced implant, DBM, and a custom healing abutment may have an advantage in retaining biologically active molecules and form a scaffold for neovascularization and osteogenesis. This treatment protocol may be a viable option for immediate implant therapy in a failed tooth with deficient buccal alveolar bone.

  3. Allogeneic Th1 cells home to host bone marrow and spleen and mediate IFNγ-dependent aplasia.

    PubMed

    Chewning, Joseph H; Zhang, Weiwei; Randolph, David A; Swindle, C Scott; Schoeb, Trenton R; Weaver, Casey T

    2013-06-01

    Bone marrow graft failure and poor graft function are frequent complications after hematopoietic stem cell transplantation and result in significant morbidity and mortality. Both conditions are associated with graft-versus-host disease (GVHD), although the mechanism remains undefined. Here we show, in 2 distinct murine models of GVHD (complete MHC- and class II-disparate) that mimic human peripheral blood stem cell transplantation, that Th1 CD4(+) cells induce bone marrow failure in allogeneic recipients. Bone marrow failure after transplantation of allogeneic naïve CD4(+) T cells was associated with increased CD4(+) Th1 cell development within bone marrow and lymphoid tissues. Using IFNγ-reporter mice, we found that Th1 cells generated during GVHD induced bone marrow failure after transfers into secondary recipients. Homing studies demonstrated that transferred Th1 cells express CXCR4, which was associated with accumulation within bone marrow and spleen. Allogeneic Th1 cells were activated by radiation-resistant host bone marrow cells and induced bone marrow failure through an IFNγ-dependent mechanism. Thus, allogeneic Th1 CD4(+) cells generated during GVHD traffic to hematopoietic sites and induce bone marrow failure via IFNγ-mediated toxicity. These results have important implications for prevention and treatment of bone marrow graft failure after hematopoietic stem cell transplantation.

  4. 31P NMR relaxation of cortical bone mineral at multiple magnetic field strengths and levels of demineralization.

    PubMed

    Seifert, Alan C; Wright, Alexander C; Wehrli, Suzanne L; Ong, Henry H; Li, Cheng; Wehrli, Felix W

    2013-09-01

    Recent work has shown that solid-state (1) H and (31) P MRI can provide detailed insight into bone matrix and mineral properties, thereby potentially enabling differentiation of osteoporosis from osteomalacia. However, (31) P MRI of bone mineral is hampered by unfavorable relaxation properties. Hence, accurate knowledge of these properties is critical to optimizing MRI of bone phosphorus. In this work, (31) P MRI signal-to-noise ratio (SNR) was predicted on the basis of T1 and T2 * (effective transverse relaxation time) measured in lamb bone at six field strengths (1.5-11.7 T) and subsequently verified by 3D ultra-short echo-time and zero echo-time imaging. Further, T1 was measured in deuterium-exchanged bone and partially demineralized bone. (31) P T2 * was found to decrease from 220.3 ± 4.3 µs to 98.0 ± 1.4 µs from 1.5 to 11.7 T, and T1 to increase from 12.8 ± 0.5 s to 97.3 ± 6.4 s. Deuteron substitution of exchangeable water showed that 76% of the (31) P longitudinal relaxation rate is due to (1) H-(31) P dipolar interactions. Lastly, hypomineralization was found to decrease T1, which may have implications for (31) P MRI based mineralization density quantification. Despite the steep decrease in the T2 */T1 ratio, SNR should increase with field strength as B0 (0.4) for sample-dominated noise and as B0 (1.1) for coil-dominated noise. This was confirmed by imaging experiments. PMID:23505120

  5. Treatment of severe post-traumatic bone defects with autologous stem cells loaded on allogeneic scaffolds.

    PubMed

    Vulcano, Ettore; Murena, Luigi; Cherubino, Paolo; Falvo, Daniele A; Rossi, Antonio; Baj, Andreina; Toniolo, Antonio

    2012-12-01

    Mesenchymal stem cells may differentiate into angiogenic and osteoprogenitor cells. The effectiveness of autologous pluripotent mesenchymal cells for treating bone defects has not been investigated in humans. We present a case series to evaluate the rationale of using nucleated cells from autologous bone marrow aspirates in the treatment of severe bone defects that failed to respond to traditional treatments. Ten adult patients (mean age, 49.6-years-old) with severe bone defects were included in this study. Lower limb bone defects were >or=5 cm3 in size, and upper limb defects .or=2 cm3. Before surgery, patients were tested for antibodies to common pathogens. Treatment consisted of bone allogeneic scaffold enriched with bone marrow nucleated cells harvested from the iliac crest and concentrated using an FDA-approved device. Postsurgery clinical and radiographic follow-up was performed at 1, 3, 6, and 12 months. To assess viability, morphology, and immunophenotype, bone marrow nucleated cells were cultured in vitro, tested for sterility, and assayed for the possible replication of adventitious (contaminating) viruses. In 9 of 10 patients, both clinical and radiographic healing of the bone defect along with bone graft integration were observed (mean time, 5.6 months); one patient failed to respond. No post-operative complications were observed. Bone marrow nucleated cells were enriched 4.49-fold by a single concentration step, and these enriched cells were free of microbial contamination. The immunophenotype of adherent cells was compatible with that of mesenchymal stem cells. We detected the replication of Epstein-Barr virus in 2/10 bone marrow cell cultures tested. Hepatitis B virus, cytomegalovirus, parvovirus B19, and endogenous retrovirus HERV-K replication were not detected. Overall, 470 to 1,150 million nucleated cells were grafted into each patient. This case series, with a mean follow-up of almost 2 years, demonstrates that an allogeneic bone scaffold

  6. Adult allogeneic bone marrow transplantation: initial experience in the University Hospital, Kuala Lumpur.

    PubMed

    Teh, A; Bosco, J J; Leong, K W; Saw, M H; Menaka, N; Devashanti, P

    1997-03-01

    Prior to 1993, bone marrow transplantation for adult patients was not available in Malaysia. Adult allogeneic bone marrow transplantation commenced in Malaysia when the first transplant was conducted at the University Hospital, Kuala Lumpur on 2 November 1993. Up till July 1995, 10 adult bone marrow transplants had been conducted at the University Hospital. Five patients had acute myeloid leukaemia in first remission, 4 had chronic myeloid leukaemia and 1 had acute lymphoblastic leukaemia in first partial remission. The age range of patients at the time of transplant is 16-40 years (mean 25.5 years). All patients engrafted successfully and the survival for the first 100 days post-transplant is 90%. One patient demonstrated haematological relapse post-transplant but achieved remission with donor buffy-coat infusion. The mean drug cost incurred was RM28,269 for the first 100 days. Locally available adult allogeneic bone marrow transplantation is safe, affordable and has comparable results with reputable overseas transplant centres.

  7. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma.

    PubMed

    Nysom, K; Holm, K; Hesse, B; Ulrik, C S; Jacobsen, N; Bisgaard, H; Hertz, H

    1996-05-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had significantly reduced transfer factor, total lung capacity, and forced vital capacity (-1.0, -1.2, and -0.8 SD score, respectively), and increased ratio of forced expiratory volume in one second to forced vital capacity (+0.9 SD score). None of the patients had pulmonary symptoms, and changes were unrelated to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation.

  8. Effects of demineralization on the stable isotope analysis of bone samples

    PubMed Central

    Tomaszewicz, Calandra Turner; Seminoff, Jeffrey A.; Ramirez, Matthew D.; Kurle, Carolyn M.

    2015-01-01

    Rationale The sampling of sequential, annually formed bone growth layers for stable carbon (δ13C values) and nitrogen (δ15N values) isotope analysis (SIA) can provide a time series of foraging ecology data. To date, no standard protocol exists for the pre-SIA treatment of cortical samples taken from fresh, modern, bones. Methods Based on the SIA of historical bone, it is assumed that fresh bone samples must be pre-treated with acid prior to SIA. Using an elemental analyzer coupled to an isotope ratio mass spectrometer to measure stable carbon and nitrogen ratios, we tested the need to acidify cortical bone powder with 0.25M HCl prior to SIA to isolate bone collagen for the determination of δ13C and δ15N values. We also examined the need for lipid extraction to remove potential biases related to δ13C analysis, based on a C:N ratio threshold of 3.5. Results It was found that acidification of micromilled cortical bone samples from marine turtles does not affect their δ15N values, and the small effect acidification has on δ13C values can be mathematically corrected for, thus eliminating the need for pre-SIA acidification of cortical bone. The lipid content of the cortical bone samples was low, as measured by their C:N ratios, indicating that lipid extracting cortical bone samples from modern marine turtles is unnecessary. Conclusions We present a standard protocol for testing fresh, modern cortical bone samples prior to SIA, facilitating direct comparison of future studies. Based on the results obtained from marine turtle bones, pre-acidification and lipid removal of cortical bone are not recommended. This is especially useful as there is frequently not enough bone material removed via micromilling of sequential growth layers to accommodate both acid treatment and SIA. PMID:26411509

  9. A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration

    NASA Astrophysics Data System (ADS)

    Meng, Qingyang; Man, Zhentao; Dai, Linghui; Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Shao, Zhenxing; Zhu, Jingxian; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Ao, Yingfang

    2015-12-01

    Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects.

  10. A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration.

    PubMed

    Meng, Qingyang; Man, Zhentao; Dai, Linghui; Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Shao, Zhenxing; Zhu, Jingxian; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Ao, Yingfang

    2015-12-03

    Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects.

  11. A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration

    PubMed Central

    Meng, Qingyang; Man, Zhentao; Dai, Linghui; Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Shao, Zhenxing; Zhu, Jingxian; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Ao, Yingfang

    2015-01-01

    Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects. PMID:26632447

  12. New bone formation by allogeneic mesenchymal stem cell transplantation in a patient with perinatal hypophosphatasia.

    PubMed

    Tadokoro, Mika; Kanai, Rie; Taketani, Takeshi; Uchio, Yuji; Yamaguchi, Seiji; Ohgushi, Hajime

    2009-06-01

    Mesenchymal stem cells (MSCs) can show osteogenic differentiation capability when implanted in vivo, as well as cultured in vitro; therefore we attempted to use allogeneic MSCs for an 8-month-old patient with hypophosphatasia. MSCs were obtained by culture expansion of fresh marrow from the patient's father. Some of the MSCs were further cultured under osteogenic conditions on a culture dish or porous hydroxyapatite ceramics, resulting in cultured osteoblasts and osteogenic constructs, respectively. The MSCs and osteoblasts were injected into the patient, and the constructs were implanted locally. After traditional bone marrow transplantation, the MSCs, osteoblasts, and osteogenic constructs were used for treatment and to improve the patient's respiratory condition and skeletal abnormality. The condition worsened again, and an MSC booster shot was administered. At the same time, the construct was retrieved. The respiratory condition improved, and the retrieved construct showed de novo bone derived from both donor and patient cells. We demonstrated the importance of allogeneic MSC transplantation for hypophosphatasia and the constructs as an alternative to bone fragments that provided further osteogenic capability in the patient. PMID:19446101

  13. Allogeneic bone marrow transplantation in hematologic disorders of childhood: new trends and controversies.

    PubMed

    Barth, E; Malorgio, C; Tamaro, P

    2000-11-01

    Bone marrow transplantation (BMT) represents an important therapeutic choice for several kinds of disorders: hematologic, metabolic and neoplastic pathologies can be treated with this strategy. The aim of this article is to describe the main indications for allogeneic BMT in haematologic disorders of childhood and possible problems related to this procedure. We consider only hematologic aspects, paying particular attention to unusual disorders of infancy as myelodysplastic syndromes and aplastic anemia. We also consider quality of life after a BMT in patients with sickle cell anemia and thalassemia major and compare this with quality of life of patients receiving chronic periodic blood transfusions.

  14. 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.

  15. Bone Marrow GvHD after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Szyska, Martin; Na, Il-Kang

    2016-01-01

    The bone marrow is the origin of all hematopoietic lineages and an important homing site for memory cells of the adaptive immune system. It has recently emerged as a graft-versus-host disease (GvHD) target organ after allogeneic stem cell transplantation (alloHSCT), marked by depletion of both hematopoietic progenitors and niche-forming cells. Serious effects on the restoration of hematopoietic function and immunological memory are common, especially in patients after myeloablative conditioning therapy. Cytopenia and durable immunodeficiency caused by the depletion of hematopoietic progenitors and destruction of bone marrow niches negatively influence the outcome of alloHSCT. The complex balance between immunosuppressive and cell-depleting treatments, GvHD and immune reconstitution, as well as the desirable graft-versus-tumor (GvT) effect remains a great challenge for clinicians. PMID:27066008

  16. Effects of T cell depletion in radiation bone marrow chimeras. III. Characterization of allogeneic bone marrow cell populations that increase allogeneic chimerism independently of graft-vs-host disease in mixed marrow recipients

    SciTech Connect

    Sykes, M.; Chester, C.H.; Sundt, T.M.; Romick, M.L.; Hoyles, K.A.; Sachs, D.H. )

    1989-12-01

    The opposing problems of graft-vs-host disease vs failure of alloengraftment severely limit the success of allogeneic bone marrow transplantation as a therapeutic modality. We have recently used a murine bone marrow transplantation model involving reconstitution of lethally irradiated mice with mixtures of allogeneic and syngeneic marrow to demonstrate that an allogeneic bone marrow subpopulation, removed by T cell depletion with rabbit anti-mouse brain serum and complement (RAMB/C), is capable of increasing levels of allogeneic chimerism. This effect was observed in an F1 into parent genetic combination lacking the potential for graft-vs-host disease, and radiation protection studies suggested that it was not due to depletion of stem cells by RAMB/C. We have now attempted to characterize the cell population responsible for increasing allogeneic chimerism in this model. The results indicate that neither mature T cells nor NK cells are responsible for this activity. However, an assay involving mixed marrow reconstitution in an Ly-5 congenic strain combination was found to be more sensitive to small degrees of stem cell depletion than radiation protection assays using three-fold titrations of bone marrow cells. Using this assay, we were able to detect some degree of stem cell depletion by treatment with RAMB/C, but not with anti-T cell mAb. Nevertheless, if the effects of alloresistance observed in this model are considered, the degree of stem cell depletion detected by such mixing studies in insufficient to account for the effects of RAMB/C depletion on levels of allogeneic chimerism, suggesting that another cell population with this property remains to be identified.

  17. Detection of demineralization in rat legs using multiple-angle x-ray bone densitometry

    NASA Astrophysics Data System (ADS)

    Jordan, Lawrence M.; DiBianca, Frank A.; Sebes, Jeno I.; Thomason, Donald B.; Zeman, Herbert D.; Davis, Peter G.; Kambeyanda, Dona; Li, Gao; Lovhoiden, Gunnar

    1994-05-01

    A method utilizing digital dual-energy subtraction X-ray radiography for measuring calcium densities localized to the cortical and cancellous regions of bone cross sections is described. The method is being used to study calcium loss in femurs of two differently treated groups of rats. In each experimental cohort, one group of rats is restrained from weightbearing on hind limbs by suspension from a tail harness. The other (control) group is allowed normal weightbearing on all limbs. The densitometry data for each rat leg consists of six X-ray projection images acquired at roughly equal angles about the bone axis by an intensifying screen/CCD camera imaging system. Images of bone cross sections are reconstructed by application of a maximum entropy algorithm constrained by the six projection images. The observed density data are further discriminated into cortical, cancellous and external regions on the basis of reference levels found on image density histograms.

  18. Dual luciferase labelling for non-invasive bioluminescence imaging of mesenchymal stromal cell chondrogenic differentiation in demineralized bone matrix scaffolds.

    PubMed

    Vilalta, Marta; Jorgensen, Christian; Dégano, Irene R; Chernajovsky, Yuti; Gould, David; Noël, Danièle; Andrades, José A; Becerra, José; Rubio, Nuria; Blanco, Jerónimo

    2009-10-01

    Non-invasive bioluminescence imaging (BLI) to monitor changes in gene expression of cells implanted in live animals should facilitate the development of biomaterial scaffolds for tissue regeneration. We show that, in vitro, induction of chondrogenic differentiation in mouse bone marrow stromal cell line (CL1) and human adipose tissue derived mesenchymal stromal cells (hAMSCs), permanently transduced with a procollagen II (COL2A1) promoter driving a firefly luciferase gene reporter (PLuc) (COL2A1p.PLuc), induces PLuc expression in correlation with increases in COL2A1 and Sox9 mRNA expression and acquisition of chondrocytic phenotype. To be able to simultaneously monitor in vivo cell differentiation and proliferation, COL2A1p.PLuc labelled cells were also genetically labelled with a renilla luciferase (RLuc) gene driven by a constitutively active cytomegalovirus promoter, and then seeded in demineralized bone matrix (DBM) subcutaneously implanted in SCID mice. Non-invasive BLI monitoring of the implanted mice showed that the PLuc/RLuc ratio reports on gene expression changes indicative of cell differentiation. Large (CL1) and moderated (hAMSCs) changes in the PLuc/RLuc ratio over a 6 week period, revealed different patterns of in vivo chondrogenic differentiation for the CL1 cell line and primary MSCs, in agreement with in vitro published data and our results from histological analysis of DBM sections. This double bioluminescence labelling strategy together with BLI imaging to analyze behaviour of cells implanted in live animals should facilitate the development of progenitor cell/scaffold combinations for tissue repair.

  19. Socket preservation using demineralized freezed dried bone allograft with and without plasma rich in growth factor: A canine study

    PubMed Central

    Mogharehabed, Ahmad; Birang, Reza; Torabinia, Nakisa; Nasiri, Saman; Behfarnia, Parichehr

    2014-01-01

    Background: The accelerating effect of plasma rich in growth factors (PRGFs) in the healing of extraction sockets has been demonstrated by some studies. The aim of the present study was to histologically and histomorphometrically evaluate whether bone formation would increase by the combined use of PRGF and demineralized freeze-dried bone allograft (DFDBA). Materials and Methods: In four female dogs, the distal root of the second, third and fourth lower premolars were extracted bilaterally and the mesial roots were preserved. The extraction sockets were randomly divided into DFDBA + PRGF, DFDBA + saline or control groups. Two dogs were sacrificed after 2 weeks and two dogs were sacrificed after 6 weeks. The extraction sockets were evaluated from both histological and histomorphometrical aspects. The data were analyzed by Mann-Whitney followed by Kruskal-Wallis tests using the Statistical Package for the Social Sciences version 20 (SPSS Inc., Chicago, IL, USA). Significant levels were set at 0.05. Results: The least decrease in socket height was observed in the DFDBA + PRGF group (0.73 ± 0.42 mm). The least decrease in the coronal portion was observed in the DFDBA + PRGF group (1.38 ± 1.35 mm²). The least decrease in the middle surface was observed in the DFDBA group (0.61 ± 0.80 mm²). The least decrease in the apical portion was observed in the DFDBA group (0.34 ± 0.39 mm²). Conclusion: The present study showed better socket preservation subsequent to the application of DFDBA and PRGF combination in comparison with the two other groups. However, the difference was not statistically significant. PMID:25225559

  20. The osteogenetic efficacy of goat bone marrow-enriched self-assembly peptide/demineralized bone matrix in vitro and in vivo.

    PubMed

    Li, Zhiqiang; Hou, Tianyong; Deng, Moyuan; Luo, Fei; Wu, Xuehui; Xing, Junchao; Chang, Zhengqi; Xu, Jianzhong

    2015-04-01

    In clinical practice, the prolonged duration, high cost, critical technique requirements, and ethical issues make the classical construction method of tissue-engineered bones difficult to apply widely. The major essentials in tissue engineering strategies include seed cells, growth factors, and scaffolds. This study aimed to incorporate these factors in a rapid and cost-effective manner. A self-assembly peptide/demineralized bone matrix (SAP/DBM) composite was artificially established and used for bone marrow enrichment via a selective cell retention approach. Then, goat mesenchymal stem cells (gMSCs) were seeded onto the SAP/DBM or DBM. The proliferation status of gMSCs in different scaffolds was analyzed, and the osteogenetic efficacy was evaluated after osteogenic induction. Bilateral critical-sized femoral defects (20-mm in length) were created in goats, and then the defects were implanted with the postenriched composite or DBM. Then, bone scan imaging, micro-computed tomography (CT) analysis and histological examination were performed to assess the reparative effects of the different implants. Compared with the DBM scaffolds, the growth of gMSCs in the postenriched SAP/DBM composite was faster and the expression levels of the osteo-specific genes (i.e., alkaline phosphatase, osteocalcin, osteopontin, and runt-related transcription factor 2) were significantly higher after 14 days of osteogenic induction. More importantly, the postenriched SAP/DBM composite significantly enhanced bone metabolic activity in the defect area compared with DBM at 2 and 4 weeks postoperation. Moreover, bone reconstruction was complete in marrow-enriched SAP/DBM composite, but not in the DBM. In addition, all of the osteo-related parameters, including the ratio of bone volume to total bone volume, bone mineral density, new trabecular number, and new trabecular thickness, were significantly higher in the marrow-enriched SAP/DBM than those in the DBM. These results indicated that the

  1. The 'euthyroid sick syndrome': incidence, risk factors and prognostic value soon after allogeneic bone marrow transplantation.

    PubMed

    Vexiau, P; Perez-Castiglioni, P; Socié, G; Devergie, A; Toubert, M E; Aractingi, S; Gluckman, E

    1993-12-01

    We studied the incidence of thyroid function abnormalities observed soon after allogeneic bone marrow transplantations (BMT) and their predictive value on the overall prognosis. Free serum thyroxine, free serum triiodothyronine, total serum reverse triiodothyronine and serum thyrotropin levels were systematically measured in 78 patients before and 3 months after BMT. 41 (52%) had normal hormone levels and 37 (48%) had abnormal ones, among whom four (5%) had peripheral compensated hypothyroidism and 33 (43%) were described as having 'euthyroid sick syndrome' (low thyroxine state, or low T3 syndrome). Two factors strongly influenced the appearance of thyroid abnormalities: steroid dose at the time of thyroid function testing, and age (< or = 16 years/ > 16 years). Among the younger patients, 21 had no thyroid abnormalities, while five did. Among the older patients, 20 had no thyroid abnormalities, while 32 did (P < 0.001). The occurrence of thyroid abnormalities seemed to influence survival strongly, since the 30-month projected survival time was 83% for patients without abnormalities whereas it was 49% for patients with an abnormal profile (P < 0.001). In conclusion, evidence obtained among our population reveals that euthyroid sick syndrome indicates a poor prognosis and that it is very important to monitor thyroid hormone levels (particularly free hormones) soon after allogeneic BMT and regularly thereafter. PMID:7918043

  2. Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects: biomechanics and validation of mathematical models

    PubMed Central

    Li, Ya-jun; Zhao, Bao-lin; Lv, Hao-ze; Qin, Zhi-gang; Luo, Min

    2016-01-01

    We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects. PMID:27651781

  3. Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects: biomechanics and validation of mathematical models

    PubMed Central

    Li, Ya-jun; Zhao, Bao-lin; Lv, Hao-ze; Qin, Zhi-gang; Luo, Min

    2016-01-01

    We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.

  4. Experiment requirements: Vitamin D metabolites and bone demineralization, Spacelab 2, experiment no. 1

    NASA Technical Reports Server (NTRS)

    Schnoes, H. K.; Holton, E. M.; Thirolf, R. G.

    1978-01-01

    As a contribution toward an understanding of the molecular basis of bone loss, mineral imbalance, and increasing fecal calcium under conditions of prolonged space flight, the blood levels of biologically active vitamin D metabolites of flight crew members will be quantitatively measured. Prior to the mission, the refinement of existing and the development of new techniques for the assay of all vitamin D metabolites will provide an arsenal of methods suitable for a wide range of metabolite levels. In terms of practical application, the analysis of human and animal plasma samples, Spacelab crew plasma samples, and flight hardware are envisioned.

  5. Demineralized Bone Matrix Add-On for Acceleration of Bone Healing in Atypical Subtrochanteric Femoral Fracture: A Consecutive Case-Control Study

    PubMed Central

    Kulachote, Noratep; Sirisreetreerux, Norachart; Chanplakorn, Pongsthorn; Fuangfa, Praman; Suphachatwong, Chanyut; Wajanavisit, Wiwat

    2016-01-01

    Background. Delayed union and nonunion are common complications in atypical femoral fractures (AFFs) despite having good fracture fixation. Demineralized bone matrix (DBM) is a successfully proven method for enhancing fracture healing of the long bone fracture and nonunion and should be used in AFFs. This study aimed to compare the outcome after subtrochanteric AFFs (ST-AFFs) fixation with and without DBM. Materials and Methods. A prospective study was conducted on 9 ST-AFFs patients using DBM (DBM group) during 2013-2014 and compared with a retrospective consecutive case series of ST-AFFs patients treated without DBM (2010–2012) (NDBM group, 9 patients). All patients were treated with the same standard guideline and followed up until fractures completely united. Postoperative outcomes were then compared. Results. DBM group showed a significant shorter healing time than NDBM group (28.1 ± 14.4 versus 57.9 ± 36.8 weeks, p = 0.04). Delayed union was found in 4 patients (44%) in DBM group compared with 7 patients (78%) in NDBM group (p > 0.05). No statistical difference of nonunion was demonstrated between both groups (DBM = 1 and NDBM = 2, p > 0.05). Neither postoperative infection nor severe local tissue reaction was found. Conclusions. DBM is safe and effective for accelerating the fracture healing in ST-AFFx and possibly reduces nonunion after fracture fixation. Trial registration number is TCTR20151021001. PMID:27022610

  6. The Franco-American macaque experiment. [bone demineralization of monkeys on Space Shuttle

    NASA Technical Reports Server (NTRS)

    Cipriano, Leonard F.; Ballard, Rodney W.

    1988-01-01

    The details of studies to be carried out jointly by French and American teams on two rhesus monkeys prepared for future experiments aboard the Space Shuttle are discussed together with the equipment involved. Seven science discipline teams were formed, which will study the effects of flight and/or weightlessness on the bone and calcium metabolism, the behavior, the cardiovascular system, the fluid balance and electrolytes, the muscle system, the neurovestibular interactions, and the sleep/biorhythm cycles. New behavioral training techniques were developed, in which the animals were trained to respond to behavioral tasks in order to measure the parameters involving eye/hand coordination, the response time to target tracking, visual discrimination, and muscle forces used by the animals. A large data set will be obtained from different animals on the two to three Space Shuttle flights; the hardware technologies developed for these experiments will be applied for primate experiments on the Space Station.

  7. Successful liver allografts in mice by combination with allogeneic bone marrow transplantation

    SciTech Connect

    Nakamura, T.; Good, R.A.; Yasumizu, R.; Inoue, S.; Oo, M.M.; Hamashima, Y.; Ikehara, S.

    1986-06-01

    Successful liver allografts were established by combination with allogeneic bone marrow transplantation. When liver tissue of BALB/c (H-2d) or C57BL/6J (H-2b) mice was minced and grafted under the kidney capsules of C3H/HeN (H-2k) mice, it was rejected. However, when C3H/HeN mice were irradiated and reconstituted with T-cell-depleted BALB/c or BALB/c nu/nu bone marrow cells, or with fetal liver cells of BALB/c mice, they accepted both donor (stem-cell)-type (BALB/c) and host (thymus)-type (C3H/HeN) liver tissue. Assays for both mixed-lymphocyte reaction and induction of cytotoxic T lymphocytes revealed that the newly developed T cells were tolerant of both donor (stem-cell)-type and host (thymus)-type major histocompatibility complex determinants. We propose that liver allografts combined with bone marrow transplantation should be considered as a viable therapy for patients with liver disease such as liver cirrhosis and hepatoma.

  8. Ex Vivo Expanded Allogeneic Mesenchymal Stem Cells With Bone Marrow Transplantation Improved Osteogenesis in Infants With Severe Hypophosphatasia.

    PubMed

    Taketani, Takeshi; Oyama, Chigusa; Mihara, Aya; Tanabe, Yuka; Abe, Mariko; Hirade, Tomohiro; Yamamoto, Satoshi; Bo, Ryosuke; Kanai, Rie; Tadenuma, Taku; Michibata, Yuko; Yamamoto, Soichiro; Hattori, Miho; Katsube, Yoshihiro; Ohnishi, Hiroe; Sasao, Mari; Oda, Yasuaki; Hattori, Koji; Yuba, Shunsuke; Ohgushi, Hajime; Yamaguchi, Seiji

    2015-01-01

    Patients with severe hypophosphatasia (HPP) develop osteogenic impairment with extremely low alkaline phosphatase (ALP) activity, resulting in a fatal course during infancy. Mesenchymal stem cells (MSCs) differentiate into various mesenchymal lineages, including bone and cartilage. The efficacy of allogeneic hematopoietic stem cell transplantation for congenital skeletal and storage disorders is limited, and therefore we focused on MSCs for the treatment of HPP. To determine the effect of MSCs on osteogenesis, we performed multiple infusions of ex vivo expanded allogeneic MSCs for two patients with severe HPP who had undergone bone marrow transplantation (BMT) from asymptomatic relatives harboring the heterozygous mutation. There were improvements in not only bone mineralization but also muscle mass, respiratory function, and mental development, resulting in the patients being alive at the age of 3. After the infusion of MSCs, chimerism analysis of the mesenchymal cell fraction isolated from bone marrow in the patients demonstrated that donor-derived DNA sequences existed. Adverse events of BMT were tolerated, whereas those of MSC infusion did not occur. However, restoration of ALP activity was limited, and normal bony architecture could not be achieved. Our data suggest that multiple MSC infusions, following BMT, were effective and brought about clinical benefits for patients with lethal HPP. Allogeneic MSC-based therapy would be useful for patients with other congenital bone diseases and tissue disorders if the curative strategy to restore clinically normal features, including bony architecture, can be established.

  9. Slowly Delivered Icariin/Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells to Promote the Healing of Calvarial Critical-Size Bone Defects

    PubMed Central

    Liu, Tianlin; Luo, Yuan

    2016-01-01

    Bone tissue engineering technique is a promising strategy to repair large-volume bone defects. In this study, we developed a 3-dimensional construct by combining icariin (a small-molecule Chinese medicine), allogeneic bone marrow-derived mesenchymal stem cells (BMSCs), and a siliceous mesostructured cellular foams-poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (SMC-PHBHHx) composite scaffold. We hypothesized that the slowly released icariin could significantly promote the efficacy of SMC-PHBHHx/allogeneic BMSCs for repairing critical-size bone defects in rats. In in vitro cellular experiments, icariin at optimal concentration (10−6 mol/L) could significantly upregulate the osteogenesis- and angiogenesis-related genes and proteins, such as Runx2, ALP, osteocalcin, vascular endothelial growth factors, and fibroblast growth factors, as well as the mineralization of BMSCs. Icariin that was adsorbed onto the SMC-PHBHHx scaffold showed a slow release profile within a 2-week monitoring span. Eight weeks after implantation in calvarial critical-size bone defects, the constructs with icariin were associated with significantly higher bone volume density, trabecular thickness, trabecular number, and significantly lower trabecular separation than the constructs without icariin. Histomorphometric analysis showed that icariin was also associated with a significantly higher density of newly formed blood vessels. These data suggested a promising application potential of the icariin/SMC-PHBHHx/allogeneic BMSCs constructs for repairing large-volume bone defects in clinic. PMID:27721833

  10. A randomized controlled evaluation of alveolar ridge preservation following tooth extraction using deproteinized bovine bone mineral and demineralized freeze-dried bone allograft

    PubMed Central

    Sadeghi, Rokhsareh; Babaei, Maryam; Miremadi, S. Asghar; Abbas, Fatemeh Mashadi

    2016-01-01

    Background: Alveolar ridge preservation could be performed immediately following tooth extraction to limit dimensional changes of alveolar process due to bone resorption. The aim of this study was to compare the clinical and histologic outcomes of socket preservation using two different graft materials; deproteinized bovine bone mineral (DBBM) and demineralized freeze-dried bone allograft (DFDBA) with absorbable collagen membrane. Materials and Methods: Twenty extraction sockets in 20 patients were randomly divided into 2 treatment groups: 10 sockets were augmented with DBBM and collagen membrane whereas 10 sockets were filled with DFDBA and covered by collagen membrane. Primary closure was achieved over extraction sockets by flap advancement. Horizontal and vertical ridge dimensional changes were assessed at baseline and after 4-6 months at the time of implant placement. For histological and histomorphometrical analysis, bone samples were harvested from the augmented sites with trephine during implant surgery. All data were analyzed using SPSS version 18 (α=0.05). Results: Clinical measurements revealed that average horizontal reduction was 2.3 ± 0.64 mm for DFDBA and 2.26 ± 0.51 mm for DBBM. Mean vertical ridge resorption at buccal side was 1.29 ± 0.68 mm for DFDBA and 1.1 ± 0.17 mm for DBBM. Moreover, mean vertical ridge reduction at lingual site was 0.41 ± 0.38 mm and 0.35 ± 0.34 mm for DFDBA and DBBM, respectively. No significant differences were seen between two groups in any of those clinical parameters. Histologic analysis showed statistically significant more new bone deposition for DFDBA compared to DBBM (34.49 ± 3.19 vs. 18.76 ± 3.54) (P < 0.01). Residual graft particles were identified significantly more in DBBM (12.77 ± 1.85) than DFDBA (6.06 ± 1.02). Conclusion: Based on the findings of this study, both materials have positive effect on alveolar ridge preservation after tooth extraction, but there was more new bone formation and less

  11. A comparative evaluation of extraction socket preservation with demineralized freeze-dried bone allograft alone and along with platelet-rich fibrin: A clinical and radiographic study

    PubMed Central

    Thakkar, Dhaval J.; Deshpande, Neeraj C.; Dave, Deepak H.; Narayankar, Suraj D.

    2016-01-01

    Aims: To investigate clinically and radiographically, the bone fill in extraction sockets using demineralized freeze-dried bone allograft alone and along with platelet-rich fibrin (PRF). Materials and Methods: A randomized controlled clinical trial was carried out on 36 nonrestorable single-rooted teeth sites. Sites were randomized into demineralized freeze-dried bone allograft (DFDBA) combined with PRF - test and DFDBA - control groups using a coin toss method. After the placement of graft material, collagen membrane was used to cover it. The clinical parameters recorded were ridge width and ridge height. All the parameters were recorded at baseline and at 90 and 180 days. Statistical Analysis Used: Independent t-test and paired t-test. Results: In both groups, there is significant reduction in loss of ridge width and ridge height from baseline to 90 days (P < 0.001), baseline to 180 days (P < 0.001), and 90–180 days (P < 0.001). However, when both the groups were compared the test group favored in the reduction of ridge width while there was no statistical difference in reduction of ridge height among at different intervals. Conclusions: Although DFDBA is considered as an ideal graft material, PRF can be used as an adjunctive with DFDBA for socket preservation.

  12. A comparative evaluation of extraction socket preservation with demineralized freeze-dried bone allograft alone and along with platelet-rich fibrin: A clinical and radiographic study

    PubMed Central

    Thakkar, Dhaval J.; Deshpande, Neeraj C.; Dave, Deepak H.; Narayankar, Suraj D.

    2016-01-01

    Aims: To investigate clinically and radiographically, the bone fill in extraction sockets using demineralized freeze-dried bone allograft alone and along with platelet-rich fibrin (PRF). Materials and Methods: A randomized controlled clinical trial was carried out on 36 nonrestorable single-rooted teeth sites. Sites were randomized into demineralized freeze-dried bone allograft (DFDBA) combined with PRF - test and DFDBA - control groups using a coin toss method. After the placement of graft material, collagen membrane was used to cover it. The clinical parameters recorded were ridge width and ridge height. All the parameters were recorded at baseline and at 90 and 180 days. Statistical Analysis Used: Independent t-test and paired t-test. Results: In both groups, there is significant reduction in loss of ridge width and ridge height from baseline to 90 days (P < 0.001), baseline to 180 days (P < 0.001), and 90–180 days (P < 0.001). However, when both the groups were compared the test group favored in the reduction of ridge width while there was no statistical difference in reduction of ridge height among at different intervals. Conclusions: Although DFDBA is considered as an ideal graft material, PRF can be used as an adjunctive with DFDBA for socket preservation. PMID:27630503

  13. Iron carrier proteins facilitate engraftment of allogeneic bone marrow and enduring hemopoietic chimerism in the lethally irradiated host

    SciTech Connect

    Pierpaoli, W.; Dall'Ara, A.; Yi, C.X.; Neri, P.; Santucci, A.; Choay, J. )

    1991-04-15

    Cell-free supernatants of rabbit bone marrow were fractionated, separated, and purified by Ultrogel and Superose chromatography. A single fraction promoted engraftment of allogeneic bone marrow and enduring hemopoietic chimerism across the H-2 barrier in lethally irradiated mice. This 'bio-active' fraction, analyzed by reducing SDS-PAGE electrophoresis, and transblotted on PVDF membrane, and purified by reverse-phase HPLC and SDS-PAGE electrophoresis yielded a main prealbumin band that when examined for primary structure by Edman degradation, proved to be rabbit transferrin. This was also attested by highly specific precipitation of the prealbumin band with polyclonal antibodies to rabbit transferrin. Iron-saturated human transferrin, lactotransferrin, and egg transferrin (conalbumin) were assayed in irradiated C57BL/6 mice infused with bone marrow from histoincompatible BALB/c donors. Mice treated with iron-loaded transferrins survive and develop enduring allogeneic chimerism with no discernible signs of graft-versus-host disease. Iron carrier proteins thus provide an unique means of achieving successful engraftment of allogeneic bone marrow in immunologically hostile murine H-2 combinations.

  14. Transplantation of islet cells across major histocompatibility barriers after total lymphoid irradiation and infusion of allogeneic bone marrow cells

    SciTech Connect

    Britt, L.D.; Scharp, D.W.; Lacy, P.E.; Slavin, S.

    1982-08-01

    Diabetic Lewis rats (AgB1/L) were evaluated as recipients of allogeneic Wistar-Furth (AgB2/2) isolated adult islets without the use of standard recipient immunosuppression. One group was treated with fractionated total lymphoid irradiation (TLI) and Wistar-Furth bone marrow cell reconstitution to proven chimerism prior to islet transplantation. This group returned to a prediabetic state following Wistar-Furth islet transplantation without any evidence of rejection for 100 days posttransplant. A second group of Lewis rats received only TLI without bone marrow treatment. They gave a varying result following islet transplantation with one recipient showing evidence of prolonged islet survival. A third chimeric control group did not receive isolated islets and did not alter their diabetic state. A fourth group was not given TLI nor donor bone marrow cells and uniformly rejected their allogeneic islets by 7 days. Thus, allogeneic adult islets will survive across major rat histocompatibility barriers using TLI and donor bone marrow chimerism as the only form of immunosuppression.

  15. Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells

    PubMed Central

    2016-01-01

    Background Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds. Materials and Methods In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery. Results Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015), and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039). No failures of tendon-bone healing were noted in either group. Conclusion Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft. PMID:27606597

  16. Bone-demineralization diagnosis in a bone-tissue-skin matrix using the pulsed-chirped photothermal radar

    NASA Astrophysics Data System (ADS)

    Kaiplavil, Sreekumar; Mandelis, Andreas

    2012-02-01

    A chirped pulsed photothermal radiometric radar is introduced for the diagnosis of biological samples, especially bones with tissue and skin overlayers. The constraints imposed by the laser safety (maximum permissible exposure, MPE) ceiling on pump laser energy and the strong attenuation of thermal-wave signals in tissues significantly limit the photothermally active depth in most biological specimens to a level which is normally insufficient for practical applications (approx. 1 mm below the skin surface). A theoretical approach for improvement of signal-to-noise ratio (SNR), minimizing the static (dc) component of the photothermal signal and making use of the photothermal radiometric nonlinearity has been introduced and verified by comparing the SNR of four distinct excitation wave forms (sine-wave, square-wave, constant- width and constant duty-cycle pulses) for chirping the pump laser, under constant exposure energy. At low frequencies fixed-pulsewidth chirps of large peak power were found to be superior to all other equal-energy modalities, with an SNR improvement up to two orders of magnitude. Distinct thickness-dependent characteristic delay times in a goat bone were obtained, establishing an active depth resolution range of ca. 2.8 mm in a layered skin-fat- bone structure, a favorable result compared to the maximum reported pulsed photothermal radiometric depth resolution < 1 mm in turbid biological media. Compared to radar peak delay and amplitude, the long-delayed radar output amplitude is found to be more sensitive to subsurface conditions. Two-dimensional spatial plots of this parameter depicting the back surface conditions of bones with and without fat-tissue overlayers are presented.

  17. Humanized culture of periosteal progenitors in allogeneic serum enhances osteogenic differentiation and in vivo bone formation.

    PubMed

    Roberts, Scott J; Owen, Helen C; Tam, Wai Long; Solie, Lien; Van Cromphaut, Sophie J; Van den Berghe, Greet; Luyten, Frank P

    2014-02-01

    The translation of stem cell-based regenerative solutions from the laboratory to the clinic is often hindered by the culture conditions used to expand cell populations. Although fetal bovine serum (FBS) is widely used, regulatory bodies and safety concerns encourage alternative, xeno-free culturing practices. In an attempt to apply this approach to a bone-forming combination product of human periosteal progenitors (human periosteum derived cells) on a clinically used calcium phosphate carrier, FBS was substituted for human allogeneic serum (hAS) during cell expansion. It was found that cell proliferation was increased in hAS along with an apparent commitment to the osteogenic lineage, indicated by enhanced Runx2 expression, as well as alkaline phosphatase activity and matrix mineralization. Following analysis of signaling pathways, it was found that interferon-mediated signaling was downregulated, whereas JAK-STAT signaling was upregulated. STAT3 phosphorylation was enhanced in hAS-cultured human periosteum derived cells, inhibition of which ablated the proliferative effect of hAS. Furthermore, following in vivo implantation of hAS-cultured cells on NuOss scaffolds, enhanced bone formation was observed compared with FBS (71% increase, p < .001). Interestingly, the de novo-formed bone appeared to have a higher ratio of immature regions to mature regions, indicating that after 8 weeks implantation, tissue-formation processes were continuing. Integration of the implant with the environment appeared to be altered, with a decrease in calcium phosphate grain size and surface area, indicative of accelerated resorption. This study highlights the advantages of using humanized culture conditions for the expansion of human periosteal progenitors intended for bone regeneration.

  18. Immunological Basis of Bone Marrow Failure after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Masouridi-Levrat, Stavroula; Simonetta, Federico; Chalandon, Yves

    2016-01-01

    Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells. We next summarize the current knowledge about the contribution of inflammatory mediators to the development of PGF. In situations of chronic inflammation complicating allo-HSCT, such as graft-versus-host disease or infections, PGF seems to be essentially the result of a sustained impairment of hematopoietic stem cells (HSC) self-renewal and proliferation caused by inflammatory mediators, such as interferon-γ (IFN-γ) and tumor necrosis factor-α, and of induction of apoptosis through the Fas/Fas ligand pathway. Interestingly, the production of inflammatory molecules leads to a non-MHC restricted, bystander inhibition of hematopoiesis, therefore, representing a promising target for immunological interventions. Finally, we discuss immune-mediated impairment of bone marrow microenvironment as a potential mechanism hampering hematopoietic recovery. Better understanding of immunological mechanisms responsible for BMF syndromes after allo-HSCT may lead to the development of more efficient immunotherapeutic interventions. PMID:27695456

  19. A retrospective analysis evaluating allogeneic cancellous bone sponge for foot and ankle arthrodesis.

    PubMed

    Brigido, Stephen A; Bleazey, Scott T; Protzman, Nicole M; D'Angelantonio, Albert; Schoenhaus, Harold D

    2013-01-01

    The present retrospective case crossover study was conducted to determine the effectiveness and safety data associated with the use of an allogeneic, cancellous bone sponge in an orthopedic foot and ankle population. We reviewed the medical records of 47 subjects (80 joints) who had undergone foot and/or ankle fusion with the cancellous bone sponge. The records were reviewed up to 12 months postoperatively. The joints included in the present study were 12 ankles, 3 ankle syndesmotic fusions (with concurrent total ankle arthroplasty), 17 subtalar joints, 17 talonavicular joints, 9 calcaneocubiod joints, 1 naviculocuneiform joint, 13 first tarsometatarsal joints, 6 lesser tarsometatarsal joints, and 2 first metatarsophalangeal joints. The endpoints of the present study were solid, sustained foot and ankle fusion, as demonstrated radiographically, and the occurrence of unexpected adverse effects related to the graft. The fusion rates were compared with those reported in other studies. The patient-reported outcome variables for the present study included the visual analog pain scale and the American Orthopaedic Foot and Ankle Score. The use of a cancellous sponge showed statistically significant improvements in pain and function and comparable or better fusion rates compared with outcomes reported in other published reports.

  20. Immunological Basis of Bone Marrow Failure after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Masouridi-Levrat, Stavroula; Simonetta, Federico; Chalandon, Yves

    2016-01-01

    Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells. We next summarize the current knowledge about the contribution of inflammatory mediators to the development of PGF. In situations of chronic inflammation complicating allo-HSCT, such as graft-versus-host disease or infections, PGF seems to be essentially the result of a sustained impairment of hematopoietic stem cells (HSC) self-renewal and proliferation caused by inflammatory mediators, such as interferon-γ (IFN-γ) and tumor necrosis factor-α, and of induction of apoptosis through the Fas/Fas ligand pathway. Interestingly, the production of inflammatory molecules leads to a non-MHC restricted, bystander inhibition of hematopoiesis, therefore, representing a promising target for immunological interventions. Finally, we discuss immune-mediated impairment of bone marrow microenvironment as a potential mechanism hampering hematopoietic recovery. Better understanding of immunological mechanisms responsible for BMF syndromes after allo-HSCT may lead to the development of more efficient immunotherapeutic interventions.

  1. Bone marrow-derived hematopoietic stem and progenitor cells infiltrate allogeneic and syngeneic transplants.

    PubMed

    Fan, Z; Enjoji, K; Tigges, J C; Toxavidis, V; Tchipashivili, V; Gong, W; Strom, T B; Koulmanda, M

    2014-12-01

    Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts within 24 h posttransplantation. In fact, lineage(negative) Sca-1(+) cKit(+) ("LSK") cells, a classic signature for HSCs, were also detected among these graft infiltrating cells. Lineage negative graft infiltrating cells are functionally multi-potential as determined by a standard competitive bone marrow transplant (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative HSCs/HPCs and classic "LSK" HSCs purified from islet allograft infiltrating cells, differentiate and repopulate multiple mature blood cell phenotypes in peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts. Interestingly, "LSK" HSCs also rapidly infiltrate syngeneic islet transplants as well as allogeneic cardiac transplants and sham surgery sites. It seems likely that an inflammatory response, not an adaptive immune response to allo-antigen, is responsible for the rapid infiltration of islet and cardiac transplants by biologically active HSCs/HPCs. The pattern of hematopoietic differentiation obtained from graft infiltrating HSCs/HPCs, cells that are recovered from inflammatory sites, as noted in the competitive BMT assay, is not precisely the same as that of intramedullary HSCs. This does not refute the obvious multi-lineage potential of graft infiltrating HSCs/HPCs.

  2. 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.

  3. Success rate of implants placed in autogenous bone blocks versus allogenic bone blocks: A systematic literature review.

    PubMed

    Motamedian, Saeed Reza; Khojaste, Moein; Khojasteh, Arash

    2016-01-01

    The aim of this study is to review and compare survival/success rate of dental implants inserted in autogenous and allogenic bone blocks (ALBs). A PubMed search was performed from January 1990 to June 2014 limited to English language and human studies. Studies that reported treatment outcome of implants inserted in augmented alveolar ridges with autogenous or ALBs were included. Primary search identified 470 studies. For autogenous bone block (ABB) 36 articles and for ALB 23 articles met the inclusion criteria. Evidence on implant survival/success rate of both techniques was limited to observational studies with relatively small sample sizes. Study design, treatment methods, follow-ups, defect location, and morphology varied among studies. The range of implant survival and success rates in ABB was from 73.8% to 100% and 72.8% to 100%, respectively. The corresponding numbers for ALB were 95.3-100% and 93.7-100%, respectively. A definite conclusion could not be reached. Future studies with long-term follow-ups are required to further elucidate this issue. PMID:27563613

  4. Success rate of implants placed in autogenous bone blocks versus allogenic bone blocks: A systematic literature review

    PubMed Central

    Motamedian, Saeed Reza; Khojaste, Moein; Khojasteh, Arash

    2016-01-01

    The aim of this study is to review and compare survival/success rate of dental implants inserted in autogenous and allogenic bone blocks (ALBs). A PubMed search was performed from January 1990 to June 2014 limited to English language and human studies. Studies that reported treatment outcome of implants inserted in augmented alveolar ridges with autogenous or ALBs were included. Primary search identified 470 studies. For autogenous bone block (ABB) 36 articles and for ALB 23 articles met the inclusion criteria. Evidence on implant survival/success rate of both techniques was limited to observational studies with relatively small sample sizes. Study design, treatment methods, follow-ups, defect location, and morphology varied among studies. The range of implant survival and success rates in ABB was from 73.8% to 100% and 72.8% to 100%, respectively. The corresponding numbers for ALB were 95.3–100% and 93.7–100%, respectively. A definite conclusion could not be reached. Future studies with long-term follow-ups are required to further elucidate this issue. PMID:27563613

  5. Graft versus neuroblastoma reaction is efficiently elicited by allogeneic bone marrow transplantation through cytolytic activity in the absence of GVHD.

    PubMed

    Ash, Shifra; Gigi, Vered; Askenasy, Nadir; Fabian, Ina; Stein, Jerry; Yaniv, Isaac

    2009-12-01

    Continuous efforts are dedicated to develop immunotherapeutic approaches to neuroblastoma (NB), a tumor that relapses at high rates following high-dose conventional cytotoxic therapy and autologous bone marrow cell (BMC) reconstitution. This study presents a series of transplant experiments aiming to evaluate the efficacy of allogeneic BMC transplantation. Neuro-2a cells were found to express low levels of class I major histocompatibility complex (MHC) antigens. While radiation and syngeneic bone marrow transplantation (BMT) reduced tumor growth (P < 0.001), allogeneic BMT further impaired subcutaneous development of Neuro-2a cells (P < 0.001). Allogeneic donor-derived T cells displayed direct cytotoxic activity against Neuro-2a in vitro, a mechanism of immune-mediated suppression of tumor growth. The proliferation of lymphocytes from congenic mice bearing subcutaneous tumors was inhibited by tumor lysate, suggesting that a soluble factor suppresses cytotoxic activity of syngeneic lymphocytes. However, the growth of Neuro-2a cells was impaired when implanted into chimeric mice at various times after syngeneic and allogeneic BMT. F1 (donor-host) splenocytes were infused attempting to foster immune reconstitution, however they engrafted transiently and had no effect on tumor growth. Taken together, these data indicate: (1) Neuro-2a cells express MHC antigens and immunogenic tumor associated antigens. (2) Allogeneic BMT is a significantly better platform to develop graft versus tumor (GVT) immunotherapy to NB as compared to syngeneic (autologous) immuno-hematopoietic reconstitution. (3) An effective GVT reaction in tumor bearing mice is primed by MHC disparity and targets tumor associated antigens.

  6. Allogeneic Versus Autologous Derived Cell Sources for Use in Engineered Bone-Ligament-Bone Grafts in Sheep Anterior Cruciate Ligament Repair

    PubMed Central

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

    2015-01-01

    The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use. PMID:25397361

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

    PubMed

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

    2015-03-01

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

  8. Normalization of red cell enolase level following allogeneic bone marrow transplantation in a child with Diamond-Blackfan anemia.

    PubMed

    Park, Jeong A; Lim, Yeon Jung; Park, Hyeon Jin; Kong, Sun Young; Park, Byung Kiu; Ghim, Thad T

    2010-04-01

    We describe a girl with Diamond-Blackfan anemia with accompanying red cell enolase deficiency. At the age of 9 yr old, the patient received allogeneic bone marrow transplantation from her HLA-identical sister who had normal red cell enolase activity. While the post transplant DNA analysis with short tandem repeat has continuously demonstrated a stable mixed chimerism on follow-up, the patient remains transfusion independent and continues to show a steady increase in red cell enolase activity for over two and a half years following bone marrow transplantation.

  9. Macrophage function in murine allogeneic bone marrow radiation chimeras in the early phase after transplantation

    SciTech Connect

    Roesler, J.; Baccarini, M.; Vogt, B.; Lohmann-Matthes, M.L. )

    1989-08-01

    We tested several of the functions of macrophages (M phi) in the early phase after allogeneic bone marrow transfer to get information about this important aspect of the nonspecific immune system in the T-cell-deficient recipient. On days 3-5 after transfer, the number of M phi was reduced in the spleen, liver, lungs, and peritoneal cavity (Pe). The phagocytosis of sheep red blood cells (SRBC) by these M phi was normal or even enhanced, as in the case of Pe-M phi. Already on days 8-12 after transfer, the number of M phi in spleen and liver exceeded that of controls, whereas the number was still reduced in lungs and Pe. We examined their ability to kill P815 tumor cells, to produce tumor necrosis factor-alpha (TNF alpha), to phagocytose SRBC, to produce reactive oxygen intermediates (ROI) in vitro and to kill Listeria monocytogenes in vivo. Most functions were normal and often even enhanced, depending on the organ origin, but the ability of Pe-M phi to produce ROI was reduced. Proliferative response to macrophage colony-stimulating factor (M-CSF) and killing of YAC-1 tumor cells revealed a high frequency of macrophage precursor cells in the spleen and liver and a high natural killer (NK) activity in the liver. Altogether, enhanced nonspecific immune function, especially preactivated M phi, may enable chimeras to survive attacks by opportunistic pathogens.

  10. Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.

    PubMed

    Avery, R K; Bolwell, B J; Yen-Lieberman, B; Lurain, N; Waldman, W J; Longworth, D L; Taege, A J; Mossad, S B; Kohn, D; Long, J R; Curtis, J; Kalaycio, M; Pohlman, B; Williams, J W

    2004-12-01

    Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined. PMID:15489872

  11. Catheter-related candidemia caused by Candida lipolytica in a patient receiving allogeneic bone marrow transplantation.

    PubMed

    D'Antonio, Domenico; Romano, Ferdinando; Pontieri, Eugenio; Fioritoni, Giuseppe; Caracciolo, Claudia; Bianchini, Stefano; Olioso, Paola; Staniscia, Tommaso; Sferra, Roberta; Boccia, Stefania; Vetuschi, Antonella; Federico, Giovanni; Gaudio, Eugenio; Carruba, Giuseppe

    2002-04-01

    Candida lipolytica was recovered from the blood and the central venous catheter in a patient receiving allogeneic bone marrow transplantation. Two C. lipolytica strains from different geographical areas and the ATCC 9773 strain of C. lipolytica were used as controls. C. lipolytica was identified by standard methods. MICs indicated antifungal susceptibilities to amphotericin B, fluconazole, and itraconazole for all strains. In vitro testing and scanning electron microscopy showed that C. lipolytica was capable of producing large amounts of viscid slime material in glucose-containing solution, likely responsible for the ability of the yeast to adhere to catheter surfaces. Restriction fragment length polymorphisms revealed an identical profile for all clinical isolates, unrelated to those observed for the control strains. This finding suggested the absence of microevolutionary changes in the population of the infecting strain, despite the length of the sepsis and the potential selective pressure of amphotericin B, which had been administered to the patient for about 20 days. The genomic differences that emerged between the isolates and the control strains were indicative of a certain degree of genetic diversity between C. lipolytica isolates from different geographical areas. PMID:11923360

  12. Outcome of allogeneic bone marrow transplantation for children with advanced acute myeloid leukemia

    PubMed Central

    Nemecek, ER; Gooley, TA; Woolfrey, AE; Carpenter, PA; Matthews, DC; Sanders, JE

    2010-01-01

    Summary Allogeneic bone marrow transplantation (BMT) may offer the only chance of cure for children with acute myeloid leukemia (AML) in second complete remission (CR2) or with relapsed disease, but the outcome of these patients has not been clearly defined. We conducted a retrospective study of 58 children, median age 7.4 years (range 0.8–17.3), who received matched related or unrelated BMT at our institution for AML in CR2 (n = 12), in untreated first relapse (n = 11) or with refractory disease (n = 35), to identify risk factors associated with disease-free survival (DFS). Life threatening to fatal regimen-related toxicity was observed in 22% of patients. Estimates of DFS at 5 years (95% confidence interval) for patients in CR2, with untreated first relapse and refractory disease were 58% (27–80%), 36% (11–63%) and 9% (2–21%), respectively. Non-relapse mortality estimates were 0%, 27% (0–54%) and 17% (5–30%), and relapse estimates were 42% (14–70%), 36% (8–65%) and 74% (60–89%), respectively. Advanced disease phase and cytogenetic abnormalities at the time of transplantation were each associated with decreased DFS and increased relapse in multivariable regression models. Survival for children transplanted in CR2 or untreated first relapse is higher than that previously reported, but relapse remains the major cause of treatment failure regardless of disease stage. PMID:15361903

  13. Facilitation of allogeneic bone marrow engraftment in mice by total lymphoid irradiation combined with total-body irradiation

    SciTech Connect

    Ang, K.K.; Waer, M.; van der Schueren, E.; Vandeputte, M.

    1983-07-01

    Different groups of C57BL/Ka mice received daily fractions of 2 Gy total lymphoid irradiation (TLI) in a total dose of 34, 24, or 14 Gy. On the day after the last irradiation, 30 X 10(6) allogeneic (BALB/c) nucleated bone marrow cells were infused into the irradiated animals. When the last one or two fractions of the radiation schedule were given to the whole body (combined total lymphoid-total-body irradiation, TLBI): (1) stable bone marrow chimerism with a higher number of donor-type cells in the peripheral blood was induced in a higher percentage of mice that had received 34 Gy TLBI compared with mice that received 34 Gy TLI. (2) bone marrow chimerism could also be induced after 24 Gy or 14 Gy TLBI, whereas 24 and 14 Gy TLI alone were ineffective. The tolerance to the TLBI schedules was excellent and no clinical signs of graft-versus-host disease were noticed. It is concluded that the addition of TBI can facilitate bone marrow engraftment after TLI and drastically reduce the number of radiation fractions needed to obtain successful chimerism after allogeneic bone marrow transplantation in mice.

  14. Anti-bacterial immunity to Listeria monocytogenes in allogeneic bone marrow chimera in mice

    SciTech Connect

    Onoe, K.; Good, R.A.; Yamamoto, K.

    1986-06-01

    Protection and delayed-type hypersensitivity (DTH) to the facultative intracellular bacterium Listeria monocytogenes (L.m.) were studied in allogeneic and syngeneic bone marrow chimeras. Lethally irradiated AKR (H-2k) mice were successfully reconstituted with marrow cells from C57BL/10 (B10) (H-2b), B10 H-2-recombinant strains or syngeneic mice. Irradiated AKR mice reconstituted with marrow cells from H-2-compatible B10.BR mice, (BR----AKR), as well as syngeneic marrow cells, (AKR----AKR), showed a normal level of responsiveness to the challenge stimulation with the listeria antigens when DTH was evaluated by footpad reactions. These mice also showed vigorous activities in acquired resistance to the L.m. By contrast, chimeric mice that had total or partial histoincompatibility at the H-2 determinants between donor and recipient, (B10----AKR), (B10.AQR----AKR), (B10.A(4R)----AKR), or (B10.A(5R)----AKR), were almost completely unresponsive in DTH and antibacterial immunity. However, when (B10----AKR) H-2-incompatible chimeras had been immunized with killed L.m. before challenge with live L.m., these mice manifested considerable DTH and resistance to L.m. These observations suggest that compatibility at the entire MHC between donor and recipient is required for bone marrow chimeras to be able to manifest DTH and protection against L.m. after a short-term immunization schedule. However, this requirement is overcome by a preceding or more prolonged period of immunization with L.m. antigens. These antigens, together with marrow-derived antigen-presenting cells, can then stimulate and expand cell populations that are restricted to the MHC (H-2) products of the donor type.

  15. Successful semiallogeneic and allogeneic bone marrow reconstitution of lethally irradiated adult mice mediated by neonatal spleen cells

    SciTech Connect

    LaFace, D.M.; Peck, A.B.

    1987-11-01

    Spleens of fetal/newborn mice less than 3-4 days of age contain a naturally occurring cell population capable of suppressing T-dependent and T-independent immune responses of third-party adult cells both in vitro and in vivo. We have utilized newborn spleen cells to prevent acute graft-versus-host (GVH) disease in lethally irradiated adult hosts reconstituted with semiallogeneic or even allogeneic bone marrow cells. Pretreatment of reconstituting cell populations with newborn spleen cells reduced the incidence of GVH disease from 100% to 20% in semiallogeneic and from 100% to 40% in allogeneic combinations. Long-term-surviving reconstituted hosts proved immunologically unresponsive to both donor and host histocompatibility antigens, yet possessed a fully chimeric lymphoid system responsive to T and B cell mitogens, as well as unrelated third-party alloantigens.

  16. Specially modified stromal and immune microenvironment in injected bone marrow following intrabone transplantation facilitates allogeneic hematopoietic stem cell engraftment.

    PubMed

    Chen, Chen; Su, Yingjun; Chen, Jianwu; Song, Yajuan; Zhuang, Ran; Xiao, Bo; Guo, Shuzhong

    2016-07-01

    For allogeneic hematopoietic stem cell transplantation (HSCT), the first key step is the engraftment of hematopoietic stem cells (HSCs) across the major histocompatibility complex (MHC) barrier. Intrabone bone marrow transplantation (IBBMT) could replace more recipient stromal cells with donor cells and facilitate allogeneic organ transplantation compared with the conventional intravenous approach. However, it remains unknown whether and how IBBMT reconstructs the immune microenvironment for allogeneic HSCs. We explored where the BM microenvironment changes by determining BM stromal cell chimerism and measuring the change in CXCL-12 expression and regulatory T cells in recipient BM. We found that most stromal cells were replaced by allogeneic cells in the injected BM, with higher expression of immune regulatory cytokines (interleukin-10) compared with the contralateral BM and the intravenous group BM. This difference was independent of injury caused by intrabone injection. Consistent with the microenvironment modification, the allogeneic the engraftment rate and reconstitution capacity of HSCs were enhanced in the injected BM compared with the contralateral BM and intravenous group BM. Surgical removal of the injected bone at 7 days rather than 21 days reduced the levels of allogeneic granulocytes and HSCs in the peripheral blood. In conclusion, IBBMT specially modifies stromal cells in the injected BM which provide immune protective cues that improve the engraftment of allogeneic HSCs in an early period. PMID:27090963

  17. Allogeneic bone marrow transplantation in mice after total lymphoid irradiation: influence of breeding conditions and strain of recipient mice

    SciTech Connect

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

    1984-02-01

    Different groups of C57BL/ka or BALB/c mice received a dose of 34 Gy or 42 Gy of fractionated total lymphoid irradiation (TLI) before bone marrow transplantation with 30 x 10/sup 6/ BALB/c or C57BL nucleated bone marrow cells, respectively. BALB/c mice that were not bred in specific pathogen-free conditions before TLI showed a high morbidity and mortality rate after 34 Gy of TLI and allogeneic bone marrow transplantation as compared with BALB/c or C57BL that were bred in pathogen-free conditions before irradiation. Many of the conventionally bred BALB/c mice had clinical and histologic signs of graft-vs-host disease after TLI and allogeneic bone marrow infusion. Although leucocytosis and lymphocytosis and the immunologic competence as measured with in vitro tests were equally depressed after 34 Gy TLI in BALB/c and C57BL mice, chimerism was nevertheless significantly easier to obtain in BALB/c mice. The incidence of chimerism after TLI could be enhanced in C57BL mice by increasing the total radiation dose from 34 to 42 Gy. This augmentation of chimerism was paralleled by the induction of more suppressor cells after 42 Gy of TLI in C57BL mice.

  18. Implant Composed of Demineralized Bone and Mesenchymal Stem Cells Genetically Modified with AdBMP2/AdBMP7 for the Regeneration of Bone Fractures in Ovis aries

    PubMed Central

    Hernandez-Hurtado, Adelina A.; Lara-Arias, Jorge; Romero-Diaz, Viktor J.; Abrego-Guerra, Adalberto; Vilchez-Cavazos, Jose F.; Elizondo-Riojas, Guillermo; Martinez-Rodriguez, Herminia G.; Espinoza-Juarez, Marcela A.; Mendoza Lemus, Oscar F.

    2016-01-01

    Adipose-derived mesenchymal stem cells (ADMSCs) are inducible to an osteogenic phenotype by the bone morphogenetic proteins (BMPs). This facilitates the generation of implants for bone tissue regeneration. This study evaluated the in vitro osteogenic differentiation of ADMSCs transduced individually and in combination with adenoviral vectors expressing BMP2 and BMP7. Moreover, the effectiveness of the implant containing ADMSCs transduced with the adenoviral vectors AdBMP2/AdBMP7 and embedded in demineralized bone matrix (DBM) was tested in a model of tibial fracture in sheep. This graft was compared to ewes implanted with untransduced ADMSCs embedded in the same matrix and with injured but untreated animals. In vivo results showed accelerated osteogenesis in the group treated with the AdBMP2/AdBMP7 transduced ADMSC graft, which also showed improved restoration of the normal bone morphology.

  19. Incorporation of nanostructured hydroxyapatite and poly(N-isopropylacrylamide) in demineralized bone matrix enhances osteoblast and human mesenchymal stem cell activity.

    PubMed

    Nicoletti, Alessandro; Torricelli, Paola; Bigi, Adriana; Fornasari, Piermaria; Fini, Milena; Moroni, Lorenzo

    2015-01-01

    Demineralized bone matrix (DBM) is currently used in many clinical applications for bone augmentation and repair. DBM is normally characterized by the presence of bone morphogenetic proteins. In this study, the authors have optimized methods to obtain DBM under good manufacturing practice, resulting in enhanced bioactivity. The processed DBM can be used alone, together with nanostructured hydroxyapatite (nanoHA), or dispersed in a physiological carrier or hydrogel. In this study, osteoblasts (MG-63) and human bone marrow derived mesenchymal stem cells (hMSCs) were cultured on DBM pastes made in phosphate buffered saline solution or poly(N-isopropylacrylamide) (PNIPAAM) hydrogels with or without nanoHA. The authors observed that the presence of PNIPAAM reduced osteoblast adhesion, while the addition of nanoHA increased osteoblast adhesion, proliferation, interleukin-6 (IL-6) production, and reduced lactate dehydrogenase (LDH) production. Increasing concentrations of PNIPAAM in combination with nanoHA further increased osteoblast proliferation, and decreased IL-6 and LDH production. Incorporation of PNIPAAM in DBM enhanced hMSCs proliferation and collagen type-I production. Furthermore, a combination of PNIPAAM and nanoHA further increased alkaline phosphatase and osteocalcin production in hMSCs, independently from the concentration of PNIPAAM. This study shows that combinations of DBM with nanoHA and PNIPAAM seem to offer a promising route to enhance cell activity and induce osteogenic differentiation. PMID:26443012

  20. Multiple extramedullary relapses without bone marrow involvement after second allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.

    PubMed

    Yoo, Sang Woo; Chung, Eun Jin; Kim, Sun Young; Ko, Jeong Hee; Baek, Hey Sung; Lee, Hyun Ju; Oh, Sung Hee; Jeon, Seok Cheol; Lee, Woong Soo; Park, Chan Kum; Lee, Chul Hoon

    2012-06-01

    EMR without BM involvement after allogeneic HSCT is extremely rare, especially in children; only a few cases have been reported. A two-yr-old boy was diagnosed with AML (M4) and underwent allogeneic HSCT in first complete remission with BM from HLA-matched unrelated donor without GVHD. Four yr later, he had a BM relapse and after induction and consolidation chemotherapy, he received a second HSCT from an unrelated donor using peripheral blood stem cells. His second post-transplant course was complicated by extensive chronic GVHD involving the skin, oral cavity, and lungs, which was treated with tacrolimus and corticosteroid. Two yr later, he noticed a mild swelling in the right cheek area. The BM showed a complete remission marrow and a soft tissue biopsy was compatible with granulocytic sarcoma. PET-CT showed multifocal bone involvements. He received chemotherapy, and the chloromas decreased in size. We report a case of diffuse EMR of AML without BM involvement after a second allogeneic HSCT. PMID:21923886

  1. Chimerism of bone marrow mesenchymal stem/stromal cells in allogeneic hematopoietic cell transplantation: is it clinically relevant?

    PubMed

    Miura, Yasuo; Yoshioka, Satoshi; Yao, Hisayuki; Takaori-Kondo, Akifumi; Maekawa, Taira; Ichinohe, Tatsuo

    2013-01-01

    Multipotent mesenchymal stem/stromal cells (MSCs) have been extensively used as a transplantable cell source for regenerative medicine and immunomodulatory therapy. Specifically in allogeneic hematopoietic stem cell transplantation (HSCT), co-transplantation or post-transplant infusion of MSCs derived from bone marrow (BM) of non-self donors has been implicated in accelerating hematopoietic recovery, ameliorating graft-vs.-host disease, and promoting tissue regeneration. However, irrespective of the use of MSC co-administration, post-transplant chimerism of BM-derived MSCs after allogeneic HSCT has been reported to remain of host origin, suggesting that the infused donor MSCs are immunologically rejected or not capable of long-term engraftment in the host microenvironment. Also, hematopoietic cell allografts currently used for HSCT do not seem to contain sufficient amount of MSCs or their precursors to reconstitute host BM microenvironment. Since the toxic conditioning employed in allo-HSCT may impair the function of host MSCs to maintain hematopoietic/regenerative stem cell niches and to provide a local immunomodulatory milieu, we propose that new directions for enhancing immunohematopoietic reconstitution and tissue repair after allogeneic HSCT include the development of strategies to support functional replenishment of residual host MSCs or to support more efficient engraftment of infused donor MSCs. Future areas of research should include in vivo tracking of infused MSCs and detection of their microchimeric presence in extra-marrow sites as well as in BM.

  2. Early vancomycin-resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course.

    PubMed

    Avery, R; Kalaycio, M; Pohlman, B; Sobecks, R; Kuczkowski, E; Andresen, S; Mossad, S; Shamp, J; Curtis, J; Kosar, J; Sands, K; Serafin, M; Bolwell, B

    2005-03-01

    Vancomycin-resistant enterococcal (VRE) infection is a growing threat. We studied the incidence, risk factors, and clinical course of early-onset VRE bacteremia in allogeneic hematopoietic stem cell transplant recipients. We carried out a chart review of 281 allogeneic hematopoietic stem cell transplant recipients from 1997-2003, including preparative regimen, diagnosis, status of disease, graft-versus-host disease prophylaxis, antimicrobial therapy, and survival. VRE bacteremia developed in 12/281 (4.3%) recipients; 10 (3.6%) were within 21 days of transplant. Diagnoses were acute leukemia (7), NHL (2), and MDS (1). In all, 70% had refractory/relapsed disease; 30% were in remission. In total, 50% had circulating blasts. Nine of 10 had matched unrelated donors (7/9 with CD8+ T-cell depletion). The average time to positive VRE cultures was 15 days; average WBC was 0.05, and 80% had concomitant infections. Despite treatment, all patients died within 73 days of VRE bacteremia. Intra-abdominal complications were common. Causes of death included bacterial or fungal infection, multiorgan failure, VOD, ARDS, and relapse. A total of 60% of patients engrafted neutrophils, but none engrafted platelets. Early VRE bacteremia after allogeneic bone marrow transplant is associated with a rapidly deteriorating clinical course, although not always directly due to VRE. Early VRE may be a marker for the critical condition of these high-risk patients at the time of transplant. PMID:15640812

  3. Bone density and structure in long-term survivors of pediatric allogeneic hematopoietic stem cell transplantation.

    PubMed

    Mostoufi-Moab, Sogol; Ginsberg, Jill P; Bunin, Nancy; Zemel, Babette; Shults, Justine; Leonard, Mary B

    2012-04-01

    Children requiring allogeneic hematopoietic stem cell transplantation (alloHSCT) have multiple risk factors for impaired bone accrual. The impact of alloHSCT on volumetric bone mineral density (vBMD) and cortical structure has not been addressed. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained in 55 alloHSCT recipients, ages 5 to 26 years, a median of 7 (range, 3-16) years after alloHSCT. pQCT outcomes were converted to sex- and race- specific Z-scores relative to age based on reference data in >700 concurrent healthy participants. Cortical section modulus (Zp; a summary measure of cortical bone structure and strength), and muscle and fat area Z-scores were further adjusted for tibia length for age Z-scores. AlloHSCT survivors had lower height Z-scores (-1.21 ± 1.25 versus 0.23 ± 0.92; p < 0.001), versus reference participants; BMI Z-scores did not differ. AlloHSCT survivors had lower trabecular vBMD (-1.05; 95% confidence interval [CI], -1.33 to -0.78; p < 0.001), cortical Zp (-0.63; 95% CI, -0.91 to -0.35; p < 0.001), and muscle (-1.01; 95% CI, -1.30 to -0.72; p < 0.001) Z-scores and greater fat (0.82; 95% CI, 0.54-1.11; p < 0.001) Z-scores, versus reference participants. Adjustment for muscle deficits eliminated Zp deficits in alloHSCT. Total body irradiation (TBI) was associated with lower trabecular vBMD (-1.30 ± 1.40 versus -0.49 ± 0.88; p = 0.01) and muscle (-1.34 ± 1.42 versus -0.34 ± 0.87; p < 0.01) Z-scores. Growth hormone deficiency (GHD) was associated with lower Zp Z-scores (-1.64 ± 2.47 versus -0.28 ± 1.24; p = 0.05); however, muscle differences were not significant (-1.69 ± 1.84 versus -0.78 ± 1.01; p = 0.09). History of graft versus host disease was not associated with pQCT outcomes. In summary, alloHSCT was associated with significant deficits in trabecular vBMD, cortical geometry, and muscle area years after transplantation. TBI and

  4. Mouse bone marrow-derived mesenchymal stem cells inhibit leukemia/lymphoma cell proliferation in vitro and in a mouse model of allogeneic bone marrow transplant

    PubMed Central

    SONG, NINGXIA; GAO, LEI; QIU, HUIYING; HUANG, CHONGMEI; CHENG, HUI; ZHOU, HONG; LV, SHUQING; CHEN, LI; WANG, JIANMIN

    2015-01-01

    The allogeneic hematopoietic stem cell (HSC) transplantation of mesenchymal stem cells (MSCs) contributes to the reconstitution of hematopoiesis by ameliorating acute graft-versus-host disease (aGVHD). However, the role of MSCs in graft-versus-leukemia remains to be determined. In the present study, we co-cultured C57BL/6 mouse bone marrow (BM)-derived MSCs with A20 murine B lymphoma, FBL3 murine erythroleukemia and P388 murine acute lymphocytic leukemia cells. Cell proliferation, apoptosis, cell cycle progression and the amount of cytokine secretion were then measured using a Cell Counting kit-8, Annexin V/propidium iodide staining, flow cytometry and ELISA, respectively. We also established a model of allogeneic bone marrow transplantation (BMT) using BALB/c mice. Following the administration of A20 cells and MSCs, we recorded the symptoms and the survival of the mice for 4 weeks, assessed the T cell subsets present in peripheral blood, and, after the mice were sacrifice, we determined the infiltration of MSCs into the organs by histological staining. Our results revealed that the MSCs inhibited the proliferation of the mouse lymphoma and leukemia cells in vitro, leading to cell cycle arrest and reducing the secretion of interleukin (IL)-10. In our model of allogeneic BMT, the intravenous injection of MSCs into the mice injected wth A20 cells decreased the incidence of lymphoma, improved survival, increased the fraction of CD3+CD8+ T cells, decreased the fraction of CD3+CD4+ T cells and CD4+CD25+ T cells in peripheral blood, and ameliorated the manifestation of aGVHD. The results from the present study indicate that MSCs may be safe and effective when used in allogeneic BMT for the treatment of hemotological malignancies. PMID:25901937

  5. Evaluation of platelet-rich plasma alone or in combination with demineralized freeze dried bone allograft in treatment of periodontal infrabony defects: A comparative clinical trial

    PubMed Central

    Agarwal, Prerna; Chatterjee, Anirban; Gokhale, Shankar; Singh, Himanshu Pratap; Kandwal, Abhishek

    2016-01-01

    Aims: The use of platelet-rich plasma (PRP) alone in periodontal defects has been controversial and inconclusive. Hence, the present study was designed with the aim to assess the clinical and radiographic effectiveness of PRP alone in infrabony defects. Materials and Methods: Thirty infrabony defects were treated with either autologous PRP with open flap debridement (OFD) or autologous PRP + demineralized freeze dried bone graft (DFDBA) with OFD or OFD alone. Clinical parameters recorded were gingival index, plaque index, probing depth (PD), clinical attachment level (CAL), and gingival recession (REC). Radiographic parameters included defect depth reduction, defect resolution, and crestal bone level. All the parameters were recorded at baseline and 12 months postoperatively. Results: Mean PD reduction and CAL gain were greater in PRP + DFDBA (4.88 ± 1.12 mm and 4.26 ± 1.85 mm) and PRP (4.86 ± 2.12 mm and 4.10 ± 1.47 mm) groups than the control group (2.69 ± 1.37 mm and 1.27 ± 0.89 mm). Conclusions: Within the limits of the study, all the three groups showed significant improvement in clinical parameters from baseline to postoperative 12 months. The amount of defect depth reduction and defect resolution treated with PRP alone group were significantly < PRP + DFDBA. The results pertaining to these parameters were significantly better than the control group. PMID:27041837

  6. Effect of intrasplenic injection of allogeneic bone marrow cells on the survival of lethally X-irradiated mice

    SciTech Connect

    Imamura, M.; Miyazaki, T.; Okabe, M.; Sakurada, K.; Musashi, M.; Kawamura, K.; Hatakeyama, M.

    1983-01-01

    Radiation chimeras in mice were induced by intrasplenic injection of allogeneic bone marrow cells instead of intravenous injection. Interestingly, the survival time in X-irradiated BALB/c mice inoculated intrasplenically (i.s.) with bone marrow cells from C3H/He mice was markedly prolonged as compared with that in X-irradiated BALB/c mice inoculated i.v. with bone marrow cells from C3H/He mice. However, when C57BL/6 mice were used as donors, a significant difference between i.s. injection and i.v. injection has not been found in survival time at 60 days after X irradiation. On the contrary, when bone marrow cells from BALB/c or C57BL/6 mice were injected into X-irradiated C3H/He mice, i.s. injection gave longer survival days to recipients than did i.v. injection. Based on testing their chimerism, it was suggested that lymphoid cells of donor origin were predominantly identified in almost all BALB/c or C3H/He recipients which were inoculated i.s. with bone marrow cells from C57BL/6 mice. However, somewhat incomplete chimerism was observed when the C3H/He to BALB/c donor-recipient combination was used and vice versa.

  7. Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. I. Orthoptic liver allographs

    SciTech Connect

    Myburgh, J.A.; Smit, J.A.; Browde, S.; Hill, R.R.H.

    1980-05-01

    Fractionated total lymphoid irradiation (TLI) and allogeneic bone marrow (BM) injection have been reported to produce stable chimerism without graft-versus-host disease (GVHD) in inbred mice and rats and mongrel dogs, and transplantation tolerance for skin and heart grafts in rodents. This concept has been studied in outbred chacma baboons receiving orthotopic liver allografts with the use of five different irradiation protocols. Eight fractions of 200 rad to the whole torso, followed immediately by allogeneic BM injections, and liver grafts from the BM donors 3 to 4 weeks later resulted in markedly prolonged survivals of 63 to 106 days in four baboons (median survival of untreated controls 19 days). Only one of the four animals died directly from the effects of rejection. BM chimerism was demonstrated in two baboons. There were no clinical or histological signs of GVHD in any of the animals. Two fractions of TLI, totaling 800 rad, 23 hr apart and followed immediately by BM injection and liver grafting resulted in profound thrombocytopenia and death form intraperitoneal hemorrhage in four of five baboons. In one animal BM injection and liver transplantation were delayed for 75 days. The baboon is still alive more than 6 months later. Three groups received single doses of 300, 400, and 500 rad to the whole torso, followed by allogeneic BM injections 1 and 2 weeks later, and liver transplants from their BM donors after an additional 3 to 4 weeks. The four baboons receiving 300 rad survived for 42, 86, 123, and >180 days. Two of the four baboons receiving 400 rad died of septic intraabdominal complications with minimal or no evidence of rejection. Fourh of the five baboons receiving 500 rad died from rejection.

  8. Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis.

    PubMed

    Fiz, Francesco; Marini, Cecilia; Campi, Cristina; Massone, Anna Maria; Podestà, Marina; Bottoni, Gianluca; Piva, Roberta; Bongioanni, Francesca; Bacigalupo, Andrea; Piana, Michele; Sambuceti, Gianmario; Frassoni, Francesco

    2015-06-25

    Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation remain largely unknown. We applied a computational quantification software application to hybrid 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images to assess activity and distribution of the hematopoietic system throughout the whole skeleton of recently transplanted patients. Thirty-four patients underwent PET/CT 30 days after either adult stem cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord blood transplantation (CBT; n = 16). Our software automatically recognized compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV, coregistered PET data were extracted to identify the active BM (ABM) from the inactive tissue. Patients were compared with 34 matched controls chosen among a published normalcy database. Whole body ABM increased in ACT and CBT when compared with controls (12.4 ± 3 and 12.8 ± 6.8 vs 8.1 ± 2.6 mL/kg of ideal body weight [IBW], P < .001). In long bones, ABM increased three- and sixfold in CBT and ACT, respectively, compared with controls (0.9 ± 0.9 and 1.7 ± 2.5 vs 0.3 ± 0.3 mL/kg IBW, P < .01). These data document an unexpected distribution of transplanted BM into previously abandoned BM sites.

  9. Attenuation of Hepatic Graft-versus-host Disease in Allogeneic Recipients of MyD88-deficient Donor Bone Marrow

    PubMed Central

    Lim, Ji-Young; Lee, Young-Kwan; Lee, Sung-Eun; Ju, Ji-Min; Park, Gyeongsin; Choi, Eun Young

    2015-01-01

    Acute graft-versus-host-disease (GVHD) is characterized by selective damage to the liver, the skin, and the gastrointestinal tract. Following allogeneic hematopoietic stem cell transplantation, donor bone marrow (BM) cells repopulate the immune system of the recipient. We previously demonstrated that the acute intestinal GVHD (iGVHD) mortality rate was higher in MyD88-deficient BM recipients than that in the control BM recipients. In the present study, the role of MyD88 (expressed by donor BM) in the pathophysiology of hepatic GVHD (hGVHD) was examined. Unlike iGVHD, transplantation with MyD88-deficient T-cell depleted (TCD) BM attenuated hGVHD severity and was associated with low infiltration of T cells into the liver of the recipients. Moreover, GVHD hosts, transplanted with MyD88-deficient TCD BM, exhibited markedly reduced expansion of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) in the liver. Adoptive injection of the MDSC from wild type mice, but not MyD88-deficient mice, enhanced hepatic T cell infiltration in the MyD88-deficient TCD BM recipients. Pre-treatment of BM donors with LPS increased MDSC levels in the liver of allogeneic wild type BM recipients. In conclusion, hGVHD and iGVHD may occur through various mechanisms based on the presence of MyD88 in the non-T cell compartment of the allograft. PMID:26140044

  10. In Vivo Tracking of Systemically Administered Allogeneic Bone Marrow Mesenchymal Stem Cells in Normal Rats through Bioluminescence Imaging

    PubMed Central

    Cao, Juan; Hou, Shike; Ding, Hui; Liu, Ziquan; Song, Meijuan; Qin, Xiaojing; Wang, Xue; Yu, Mengyang; Sun, Zhiguang; Liu, Jinyang; Sun, Shuli; Xiao, Peixin

    2016-01-01

    Recently, mesenchymal stem cells (MSCs) are increasingly used as a panacea for multiple types of disease short of effective treatment. Dozens of clinical trials published demonstrated strikingly positive therapeutic effects of MSCs. However, as a specific agent, little research has focused on the dynamic distribution of MSCs after in vivo administration. In this study, we track systemically transplanted allogeneic bone marrow mesenchymal stem cells (BMSCs) in normal rats through bioluminescence imaging (BLI) in real time. Ex vivo organ imaging, immunohistochemistry (IHC), and RT-PCR were conducted to verify the histological distribution of BMSCs. Our results showed that BMSCs home to the dorsal skin apart from the lungs and kidneys after tail vein injection and could not be detected 14 days later. Allogeneic BMSCs mainly appeared not at the parenchymatous organs but at the subepidermal connective tissue and adipose tissue in healthy rats. There were no significant MSCs-related adverse effects except for transient decrease in neutrophils. These findings will provide experimental evidences for a better understanding of the biocharacteristics of BMSCs.

  11. In Vivo Tracking of Systemically Administered Allogeneic Bone Marrow Mesenchymal Stem Cells in Normal Rats through Bioluminescence Imaging.

    PubMed

    Cao, Juan; Hou, Shike; Ding, Hui; Liu, Ziquan; Song, Meijuan; Qin, Xiaojing; Wang, Xue; Yu, Mengyang; Sun, Zhiguang; Liu, Jinyang; Sun, Shuli; Xiao, Peixin; Lv, Qi; Fan, Haojun

    2016-01-01

    Recently, mesenchymal stem cells (MSCs) are increasingly used as a panacea for multiple types of disease short of effective treatment. Dozens of clinical trials published demonstrated strikingly positive therapeutic effects of MSCs. However, as a specific agent, little research has focused on the dynamic distribution of MSCs after in vivo administration. In this study, we track systemically transplanted allogeneic bone marrow mesenchymal stem cells (BMSCs) in normal rats through bioluminescence imaging (BLI) in real time. Ex vivo organ imaging, immunohistochemistry (IHC), and RT-PCR were conducted to verify the histological distribution of BMSCs. Our results showed that BMSCs home to the dorsal skin apart from the lungs and kidneys after tail vein injection and could not be detected 14 days later. Allogeneic BMSCs mainly appeared not at the parenchymatous organs but at the subepidermal connective tissue and adipose tissue in healthy rats. There were no significant MSCs-related adverse effects except for transient decrease in neutrophils. These findings will provide experimental evidences for a better understanding of the biocharacteristics of BMSCs. PMID:27610137

  12. Human tonsil-derived mesenchymal stromal cells enhanced myelopoiesis in a mouse model of allogeneic bone marrow transplantation

    PubMed Central

    Ryu, Jung-Hwa; Park, Minhwa; Kim, Bo-Kyung; Kim, Yu-Hee; Woo, So-Youn; Ryu, Kyung-Ha

    2016-01-01

    Mesenchymal stromal cells (MSCs) have therapeutic potential for repairing tissue damage and are involved in immune regulation. MSCs are predominantly isolated from bone marrow (BM), adipose tissue or placental tissue. Further to these well-known sources, the isolation of MSCs from human tonsils was previously reported. The aim of the present study was to investigate a potential role for tonsil-derived MSCs (T-MSCs) in BM reconstitution and application towards supplementing hematopoiesis in a mouse model of BM transplantation (BMT). Eight-week-old BALB/c female mice received 80 mg/kg busulfan (Bu)/200 mg/kg cyclophosphamide (Cy) conditioning chemotherapy for BM ablation. Subsequently, human T-MSCs were injected into the Bu/Cy-treated mice with or without BM cells (BMCs) obtained from allogeneic C57BL/6 male mice. After 3 weeks, peripheral blood and BM was collected for analysis. The red blood cell count in the group that received BMCs had almost returned to normal, whereas mononuclear cell counts and BM cellularity were most improved in the T-MSCs + BMCs group. These results indicate that the T-MSCs enhanced myelopoiesis in the allogeneic BMT mouse model, as evidenced by the restoration of BM with hematopoietic cells, as well as increased myeloid colony formation in vitro. Therefore, T-MSCs may provide a source of MSCs to facilitate myelopoiesis and megakaryocytosis following BMT. PMID:27511380

  13. In Vivo Tracking of Systemically Administered Allogeneic Bone Marrow Mesenchymal Stem Cells in Normal Rats through Bioluminescence Imaging

    PubMed Central

    Cao, Juan; Hou, Shike; Ding, Hui; Liu, Ziquan; Song, Meijuan; Qin, Xiaojing; Wang, Xue; Yu, Mengyang; Sun, Zhiguang; Liu, Jinyang; Sun, Shuli; Xiao, Peixin

    2016-01-01

    Recently, mesenchymal stem cells (MSCs) are increasingly used as a panacea for multiple types of disease short of effective treatment. Dozens of clinical trials published demonstrated strikingly positive therapeutic effects of MSCs. However, as a specific agent, little research has focused on the dynamic distribution of MSCs after in vivo administration. In this study, we track systemically transplanted allogeneic bone marrow mesenchymal stem cells (BMSCs) in normal rats through bioluminescence imaging (BLI) in real time. Ex vivo organ imaging, immunohistochemistry (IHC), and RT-PCR were conducted to verify the histological distribution of BMSCs. Our results showed that BMSCs home to the dorsal skin apart from the lungs and kidneys after tail vein injection and could not be detected 14 days later. Allogeneic BMSCs mainly appeared not at the parenchymatous organs but at the subepidermal connective tissue and adipose tissue in healthy rats. There were no significant MSCs-related adverse effects except for transient decrease in neutrophils. These findings will provide experimental evidences for a better understanding of the biocharacteristics of BMSCs. PMID:27610137

  14. Chimerism of allogeneic mesenchymal cells in bone marrow, liver, and spleen after mesenchymal stem cells infusion.

    PubMed

    Meleshko, Alexander; Prakharenia, Irina; Kletski, Semen; Isaikina, Yanina

    2013-12-01

    Although an infusion of culture-expanded MSCs is applied in clinic to improve results of HSCs transplantation and for a treatment of musculoskeletal disorders, homing, and engraftment potential of culture-expanded MSC in humans is still obscure. We report two female patients who received allogeneic BM transplantation as a treatment of hematological diseases and a transplantation of MSCs from third-party male donors. Both patients died within one yr of infectious complications. Specimens of paraffin-embedded blocks of tissues from transplanted patients were taken. The aim of the study was to estimate possible homing and engraftment of allogeneic BM-derived MSCs in some tissues/organs of recipient. Sensitive real-time quantitative PCR analysis was applied with SRY gene as a target. MSC chimerism was found in BM, liver, and spleen of both patients. We conclude that sensitive RQ-PCR analysis is acceptable for low-level chimerism evaluation even in paraffin-embedded tissue specimens.

  15. Role of Demineralized Allograft Subchondral Bone in the Treatment of Shoulder Lesions of the Talus: Clinical Results With Two-Year Follow-Up.

    PubMed

    Galli, Melissa M; Protzman, Nicole M; Bleazey, Scott T; Brigido, Stephen A

    2015-01-01

    Cystic osteochondral lesions of the talus present a considerable challenge for foot and ankle surgeons. The purpose of the present study was to evaluate the effect of a medial malleolar osteotomy and implantation of demineralized allograft subchondral bone on pain and function 2 years after surgery. For inclusion, patients demonstrated radiographic evidence of a medial cystic full-thickness osteochondral defect of the talus and previously failed microfracture (N = 12). We hypothesized that improvements in pain and disability would be maintained across time. Compared with the preoperative values, 2 years after surgery, pain and disability had significantly reduced (p < .001). Significant reductions had occurred in postoperative pain from 6 months to 1 year (p = .001) and from 6 months to 2 years (p = .005). Similarly, significant reductions had occurred in postoperative disability from 6 months to 1 year (p = .008) and from 6 months to 2 years (p = .03). The reductions in postoperative pain and disability were maintained from 1 year to 2 years (p ≥ .79). Multiple regression analyses identified depression as a predictor of 2-year postoperative pain (R(2) = 0.36, p = .04). No variables were identified as significant predictors of postoperative disability at 2 years. Other than 1 previously reported peroneal deep venous thrombosis, no additional complications occurred. With successful graft incorporation, no inflammatory response, and no additional complications, the allograft subchondral plug appears to successfully treat osteochondral lesions of the talus and maintain improvements in pain and disability at intermediate follow-up.

  16. Allogeneic bone marrow transplantation in a 7-year-old girl with congenital erythropoietic porphyria: a treatment dilemma.

    PubMed

    Taibjee, S M; Stevenson, O E; Abdullah, A; Tan, C Y; Darbyshire, P; Moss, C; Goodyear, H; Heagerty, A; Whatley, S; Badminton, M N

    2007-03-01

    Congenital erythropoietic porphyria (CEP, Günther's disease) has a very variable phenotype. In the more severely affected, bone marrow transplantation (BMT) is potentially curative, but is not without risks. We describe a 7-year-old girl with CEP characterized by severe photosensitivity but only mild anaemia, in whom the difficult decision to proceed with allogeneic BMT was made after discussion in a multidisciplinary team. She has shown successful engraftment, accompanied by biochemical and clinical resolution of her metabolic disease. She remains well 3 years later, the oldest patient with CEP receiving BMT to survive beyond 12 months. However, she has experienced significant morbidity including florid cutaneous graft-versus-host disease with postinflammatory hypopigmentation. Her case is important in highlighting the delay in diagnosis not uncommon in this condition and the complex decision-making process involved in proceeding with BMT.

  17. Proposal of an algorithm for analysis of bone demineralization using synchrotron radiation X-ray μCT images

    NASA Astrophysics Data System (ADS)

    Pinheiro, Christiano Jorge Gomes; de Moura Meneses, Anderson Alvarenga; Braz, Delson; de Oliveira, Luís Fernando; Cely Rodrigues Barroso, Regina

    2014-02-01

    Research on radiation effects on bony tissue, osteoporosis and other diseases demands the assessment of bone structures. Synchrotron Radiation (SR) X-ray micro-Computed Tomography (μCT) is an imaging technique that allows the investigation of such structures in the micrometer level. With the high coherence as well as the monochromaticity of the SR beam, it is possible to assess pathological conditions in those structures accurately, providing quantitative information for decision making. Topology and Histomorphometry provide parameters which describe the relationships between pores, canals and the connectivity in structures. Thus, with periodical assessment of the bone structure by SR-μCT imaging, it is possible to verify the evolution of a disease or the impact of a treatment. In the present summary we describe the application of Topology concepts for quantitative assessment of bone structures in the analysis of SR-μCT images acquired at the Elettra Laboratory (Trieste, Italy).

  18. Effects of T cell depletion in radiation bone marrow chimeras. II. Requirement for allogeneic T cells in the reconstituting bone marrow inoculum for subsequent resistance to breaking of tolerance

    SciTech Connect

    Sykes, M.; Sheard, M.A.; Sachs, D.H.

    1988-08-01

    The ability of normal recipient-type lymphocytes to break tolerance in long-term allogenic radiation chimeras has been investigated. Reconstitution of lethally irradiated mice with a mixture of syngeneic and allogeneic T cell-depleted (TCD) bone marrow (BM) has previously been shown to lead to mixed chimerism and permanent, specific tolerance to donor and host alloantigen (3-5). If allogeneic T cells are not depleted from the reconstituting inoculum, complete allogeneic chimerism results; however, no clinical evidence for GVHD is observed, presumably due to the protective effect provided by syngeneic TCD BM. This model has now been used to study the effects of allogenic T cells administered in reconstituting BM inocula on stability of long-term tolerance. We have attempted to break tolerance in long-term chimeras originally reconstituted with TCD or non-TCD BM by challenging them with inocula containing normal, nontolerant recipient strain lymphocytes. tolerance was broken with remarkable ease in recipients of mixed marrow inocula in which both original BM components were TCD. In contrast, tolerance in chimeras originally reconstituted with non-TCD allogeneic BM was not affected by such inocula. Susceptibility to loss of chimerism and tolerance was not related to initial levels of chimerism per se, but rather to T cell depletion of allogeneic BM, since chimeras reconstituted with TCD allogeneic BM alone (mean level of allogeneic chimerism 98%) were as susceptible as mixed chimeras to the tolerance-breaking effects of such inocula. The possible contribution of GVH reactivity to this resistance was investigated using an F1 into parent strain combination. In these animals, the use of non-TCD F1 BM inocula for reconstitution did not lead to resistance to the tolerance-breaking effects of recipient strain splenocytes.

  19. Prevention of bone demineralization by calcium supplementation in precocious puberty during gonadotropin-releasing hormone agonist treatment.

    PubMed

    Antoniazzi, F; Bertoldo, F; Lauriola, S; Sirpresi, S; Gasperi, E; Zamboni, G; Tatò, L

    1999-06-01

    We have previously demonstrated a negative impact on peak bone mass in girls with precocious puberty treated with GnRH agonist (GnRHa). Several studies have shown that a high calcium intake positively influences bone mass in prepubertal girls and leads to a higher peak bone mass. The aim of this study was to evaluate the effect of calcium supplementation in girls with precocious puberty during GnRHa treatment. Forty girls affected by true central precocious puberty and treated with the GnRHa triptorelin were studied for 2 yr. After diagnosis, the patients were randomly assigned to three groups: group A, treated only with GnRHa; group B, treated for 12 months solely with GnRHa and then supplemented with calcium gluconolactate/carbonate (1 g calcium/day in two doses) for 12 months; and group C, treated from the beginning with combined GnRHa and calcium. Bone mineral density (BMD) at the lumbar spine was measured by dual energy x-ray absorptiometry at the beginning of the study and after 12 and 24 months and was expressed as the calculated true volumetric density (BMDv) in milligrams per cm3. Group A showed a decrease in absolute BMDv levels, in SD score for chronological age (CA), and even more in SD score for bone age (BA). Group B showed the same behavior during the first year, but this trend was reversed in the second year, when calcium supplementation was added to GnRHa treatment. Group C showed an increase in absolute BMDv levels and in SD score for CA and BA. BMDv variations (expressed as absolute values, SD score for CA, and SD score for BA) became statistically significant at 24 months between groups C and A (P = 0.036, P = 0.032, and P = 0.025, respectively). The behavior of the lumbar spine BMDv in the three groups is consistent with a positive effect of calcium supplementation during GnRHa treatment. In calcium-supplemented patients, the normal process of bone mass accretion at puberty is preserved despite GnRHa treatment. Therefore, the reduction in BMD

  20. Second allogeneic hematopoietic cell transplantation for Patients with Fanconi anemia and Bone Marrow Failure

    PubMed Central

    Ayas, Mouhab; Eapen, Mary; Le-Rademacher, Jennifer; Carreras, Jeanette; Abdel-Azim, Hisham; Alter, Blanche P.; Anderlini, Paolo; Battiwalla, Minoo; Bierings, Marc; Buchbinder, David K.; Bonfim, Carmem; Camitta, Bruce M.; Fasth, Anders L.; Gale, Robert Peter; Lee, Michelle A.; Lund, Troy C.; Myers, Kasiani C.; Olsson, Richard F.; Page, Kristin M.; Prestidge, Tim D.; Radhi, Mohamed; Shah, Ami J.; Schultz, Kirk R.; Wirk, Baldeep; Wagner, John E.; Deeg, H. Joachim

    2015-01-01

    Second allogeneic hematopoietic cell transplantation (HCT) is the only salvage option for those for develop graft failure after their first HCT. Data on outcomes after second HCT in Fanconi anemia (FA) are scarce. We report outcomes after second allogeneic HCT for FA (n=81). The indication for second HCT was graft failure after the first HCT. Transplants occurred between 1990 and 2012. The timing of second transplantation predicted subsequent graft failure and survival. Graft failure was high when the second transplant occurred less than 3 months from the first. The 3-month probability of graft failure was 69% when the interval between first and second transplant was less than 3 months compared to 23% when the interval was longer (p<0.001). Consequently, survival rates were substantially lower when the interval between first and second transplant was less than 3 months, 23% at 1-year compared to 58%, when the interval was longer (p=0.001). The corresponding 5-year probabilities of survival were 16% and 45%, respectively (p=0.006). Taken together, these data suggest that fewer than half of FA patients undergoing a second HCT for graft failure are long-term survivors. There is an urgent need to develop strategies to lower graft failure after first HCT. PMID:26116087

  1. Second Allogeneic Hematopoietic Cell Transplantation for Patients with Fanconi Anemia and Bone Marrow Failure.

    PubMed

    Ayas, Mouhab; Eapen, Mary; Le-Rademacher, Jennifer; Carreras, Jeanette; Abdel-Azim, Hisham; Alter, Blanche P; Anderlini, Paolo; Battiwalla, Minoo; Bierings, Marc; Buchbinder, David K; Bonfim, Carmem; Camitta, Bruce M; Fasth, Anders L; Gale, Robert Peter; Lee, Michelle A; Lund, Troy C; Myers, Kasiani C; Olsson, Richard F; Page, Kristin M; Prestidge, Tim D; Radhi, Mohamed; Shah, Ami J; Schultz, Kirk R; Wirk, Baldeep; Wagner, John E; Deeg, H Joachim

    2015-10-01

    A second allogeneic hematopoietic cell transplantation (HCT) is the sole salvage option for individuals who develop graft failure after their first HCT. Data on outcomes after second HCT in patients with Fanconi anemia (FA) are scarce. Here we report outcomes after second allogeneic HCT for FA (n = 81). The indication for second HCT was graft failure after the first HCT. Transplantations were performed between 1990 and 2012. The timing of the second HCT predicted subsequent graft failure and survival. Graft failure was high when the second HCT was performed less than 3 months from the first. The 3-month probability of graft failure was 69% when the interval between the first HCT and second HCT was less than 3 months, compared with 23% when the interval was longer (P < .001). Consequently, the 1-year survival rate was substantially lower when the interval between the first and second HCTs was less than 3 months compared with longer (23% vs 58%; P = .001). The corresponding 5-year probability of survival was 16% and 45%, respectively (P = .006). Taken together, these data suggest that fewer than one-half of patients with FA undergoing a second HCT for graft failure are long-term survivors. There is an urgent need to develop strategies to reduce the rate of graft failure after first HCT. PMID:26116087

  2. Long-term outcomes of the use of allogeneic, radiation-sterilised bone blocks in reconstruction of the atrophied alveolar ridge in the maxilla and mandible.

    PubMed

    Krasny, Marta; Krasny, Kornel; Fiedor, Piotr; Zadurska, Małgorzata; Kamiński, Artur

    2015-12-01

    Increasingly dental surgeons face the challenge of reconstruction of the height and/or thickness of the alveolar ridge as more and more patients wish to have permanent restoration of their dental defects based on intraosseous implants. Evaluation of human allogeneic bone tissue grafts in reconstruction of atrophied alveolar ridge as a pre-implantation procedure. The material comprised 21 patients aged 19-63, treated between 2009 and 2012 by the same surgeon. Restoration of bone tissue defects was performed with allogeneic, frozen, radiation-sterilised, corticocancellous blocks. The study included 26 grafting procedures with 7 procedures consisting in reconstruction of the alveolar ridge in the mandible and 19 in the maxilla. In all the cases the atrophied alveolar ridge was successfully reconstructed, which allowed placement of intraosseous implants in compliance with the initial treatment plan. After the treatment was completed the patients reported for follow-up annually. The average time of follow-up amounted to 39 months (28-50 months). None of the implants was lost during the follow-up period. There was one case of gingival recession causing aesthetics deterioration of the prosthetic restoration. In three cases the connector became unscrewed partially, which was corrected at the same visit. Frozen, radiation-sterilised, allogeneic bone blocks constitute good and durable bone-replacement material allowing effective and long-lasting reconstruction of the atrophied alveolar ridge to support durable, implant-based, prosthetic restoration.

  3. Long-term outcomes of the use of allogeneic, radiation-sterilised bone blocks in reconstruction of the atrophied alveolar ridge in the maxilla and mandible.

    PubMed

    Krasny, Marta; Krasny, Kornel; Fiedor, Piotr; Zadurska, Małgorzata; Kamiński, Artur

    2015-12-01

    Increasingly dental surgeons face the challenge of reconstruction of the height and/or thickness of the alveolar ridge as more and more patients wish to have permanent restoration of their dental defects based on intraosseous implants. Evaluation of human allogeneic bone tissue grafts in reconstruction of atrophied alveolar ridge as a pre-implantation procedure. The material comprised 21 patients aged 19-63, treated between 2009 and 2012 by the same surgeon. Restoration of bone tissue defects was performed with allogeneic, frozen, radiation-sterilised, corticocancellous blocks. The study included 26 grafting procedures with 7 procedures consisting in reconstruction of the alveolar ridge in the mandible and 19 in the maxilla. In all the cases the atrophied alveolar ridge was successfully reconstructed, which allowed placement of intraosseous implants in compliance with the initial treatment plan. After the treatment was completed the patients reported for follow-up annually. The average time of follow-up amounted to 39 months (28-50 months). None of the implants was lost during the follow-up period. There was one case of gingival recession causing aesthetics deterioration of the prosthetic restoration. In three cases the connector became unscrewed partially, which was corrected at the same visit. Frozen, radiation-sterilised, allogeneic bone blocks constitute good and durable bone-replacement material allowing effective and long-lasting reconstruction of the atrophied alveolar ridge to support durable, implant-based, prosthetic restoration. PMID:26162810

  4. Space maintenance in autogenous fresh demineralized tooth blocks with platelet-rich plasma for maxillary sinus bone formation: a prospective study.

    PubMed

    Kim, Eun-Suk; Kang, Ji-Yeon; Kim, Jae-Jin; Kim, Kyoung-Won; Lee, Eun-Young

    2016-01-01

    This prospective study evaluated the effectiveness of autogenous fresh demineralized tooth block (Auto-FDT block) with platelet-rich plasma (PRP) for maxillary sinus augmentation with simultaneous implant installation. Auto-FDT block with PRP was used in Group 1 (n = 15) and combined graft (allograft and xenograft) powder with PRP was used in Group 2 (n = 15). For up to 2 years after the final prosthesis was installed, clinical and radiographic examinations were performed to evaluate the amount of graft materials, residual alveolar height (RAH), sinus height (SH) after grafting, augmented graft height (AGH) and resorption height (RH). In ten cases, biopsies were harvested for histological and histomorphometric analyses. A total of 59 implants were placed in a severe atrophic posterior maxilla with less than 5 mm of RAH and sinus augmentation. None of the patients developed sinusitis or other complications, such as implant loss. The graft material extracted included one molar (or 2 premolars) in Group 1 and 1.8 cc in Group 2. The radiologic examination revealed the following average between-group difference SH (Group 1, 14.12 ± 1.63 mm vs Group 2, 16.51 ± 1.29 mm) and AGH (Group 1, 11.62 ± 2.22 mm vs Group 2, 13.65 ± 1.35 mm). However, sufficient SH and AGH were observed for the implants in the Auto-FDT block group. Two years after final prosthesis was installed, no between-group difference in the RH was observed (Group 1, 1.23 ± 0.73 mm vs Group 2, 1.77 ± 0.54 mm, P = 0.021). The histomorphometric analysis revealed no between-group difference in the new bone volume (Group 1, 23.13 ± 1.42 % vs Group 2, 24.18 ± 2.19 %, P = 0.548). The results showed that Auto-FDT block with PRP can be used in grafted sinuses for implants with only one extracted molar (or two premolars). Auto-FDT block with PRP promotes new bone formation that is comparable with combined grafts. Auto-FDT block with PRP is as an alternative to bone grafting

  5. Fate of bone marrow mesenchymal stem cells following the allogeneic transplantation of cartilaginous aggregates into osteochondral defects of rabbits.

    PubMed

    Yoshioka, Tomokazu; Mishima, Hajime; Kaul, Zeenia; Ohyabu, Yoshimi; Sakai, Shinsuke; Ochiai, Naoyuki; Kaul, Sunil C; Wadhwa, Renu; Uemura, Toshimasa

    2011-06-01

    The purpose of this study was to track mesenchymal stem cells (MSCs) labelled with internalizing quantum dots (i-QDs) in the reparative tissues, following the allogeneic transplantation of three-dimensional (3D) cartilaginous aggregates into the osteochondral defects of rabbits. QDs were conjugated with a unique internalizing antibody against a heat shock protein-70 (hsp70) family stress chaperone, mortalin, which is upregulated and expressed on the surface of dividing cells. The i-QDs were added to the culture medium for 24 h. Scaffold-free cartilaginous aggregates formed from i-QD-labelled MSCs (i-MSCs), using a 3D culture system with chondrogenic supplements for 1 week, were transplanted into osteochondral defects of rabbits. At 4, 8 and 26 weeks after the transplantation, the reparative tissues were evaluated macroscopically, histologically and fluoroscopically. At as early as 4 weeks, the defects were covered with a white tissue resembling articular cartilage. In histological appearance, the reparative tissues resembled hyaline cartilage on safranin-O staining throughout the 26 weeks. In the deeper portion, subchondral bone and bone marrow were well remodelled. On fluoroscopic evaluation, QDs were tracked mainly in bone marrow stromata, with some signals detected in cartilage and the subchondral bone layer. We showed that the labelling of rabbit MSCs with anti-mortalin antibody-conjugated i-QDs is a tolerable procedure and provides a stable fluorescence signal during the cartilage repair process for up to 26 weeks after transplantation. The results suggest that i-MSCs did not inhibit, and indeed contributed to, the regeneration of osteochondral defects.

  6. Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia

    PubMed Central

    Arai, Yasuyuki; Kondo, Tadakazu; Yamazaki, Hirohito; Takenaka, Katsuto; Sugita, Junichi; Kobayashi, Takeshi; Ozawa, Yukiyasu; Uchida, Naoyuki; Iwato, Koji; Kobayashi, Naoki; Takahashi, Yoshiyuki; Ishiyama, Ken; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Mori, Takehiko; Teshima, Takanori

    2016-01-01

    Allogeneic bone marrow transplantation is an essential therapy for acquired aplastic anemia and prognosis has recently improved. However, engraftment failure and graft-versus-host disease are potential fatal complications. Various risk factors for poor prognosis have been identified, such as patient age and human-leukocyte antigen disparity, but the relationship between donor age and prognosis is still unknown. Therefore, we performed a cohort study to compare the prognosis of unrelated bone marrow transplantation from younger and older donors using the registry database in Japan. We evaluated 427 patients (age 16–72 years) with aplastic anemia who underwent bone marrow transplantation from younger (≤39 years, n=281) or older (≥40 years, n=146) unrelated donors. Overall survival of the older donor group was significantly inferior to that of the younger donor group (adjusted hazard ratio 1.64; 95% confidence interval 1.15–2.35; P<0.01). The incidence of fatal infection was significantly higher in the older donor group (13.7% vs. 7.5%; P=0.03). Primary engraftment failure and acute graft-versus-host disease were significantly more frequent in the older donor group (9.7% vs. 5.0%; adjusted hazard ratio 1.30; P=0.01, and 27.1% vs. 19.7%; adjusted hazard ratio 1.56; P=0.03, respectively). Acute graft-versus-host disease was related to a worse prognosis in the whole cohort. This study showed the inferiority of older donors in aplastic anemia; thus, donor age should be considered when multiple donors are available. A large-scale prospective study is warranted to establish a better donor selection algorithm for bone marrow transplantation in aplastic anemia. PMID:26858357

  7. Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia.

    PubMed

    Arai, Yasuyuki; Kondo, Tadakazu; Yamazaki, Hirohito; Takenaka, Katsuto; Sugita, Junichi; Kobayashi, Takeshi; Ozawa, Yukiyasu; Uchida, Naoyuki; Iwato, Koji; Kobayashi, Naoki; Takahashi, Yoshiyuki; Ishiyama, Ken; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Mori, Takehiko; Teshima, Takanori

    2016-05-01

    Allogeneic bone marrow transplantation is an essential therapy for acquired aplastic anemia and prognosis has recently improved. However, engraftment failure and graft-versus-host disease are potential fatal complications. Various risk factors for poor prognosis have been identified, such as patient age and human-leukocyte antigen disparity, but the relationship between donor age and prognosis is still unknown. Therefore, we performed a cohort study to compare the prognosis of unrelated bone marrow transplantation from younger and older donors using the registry database in Japan. We evaluated 427 patients (age 16-72 years) with aplastic anemia who underwent bone marrow transplantation from younger (≤39 years, n=281) or older (≥40 years, n=146) unrelated donors. Overall survival of the older donor group was significantly inferior to that of the younger donor group (adjusted hazard ratio 1.64; 95% confidence interval 1.15-2.35; P<0.01). The incidence of fatal infection was significantly higher in the older donor group (13.7% vs. 7.5%; P=0.03). Primary engraftment failure and acute graft-versus-host disease were significantly more frequent in the older donor group (9.7% vs. 5.0%; adjusted hazard ratio 1.30; P=0.01, and 27.1% vs. 19.7%; adjusted hazard ratio 1.56; P=0.03, respectively). Acute graft-versus-host disease was related to a worse prognosis in the whole cohort. This study showed the inferiority of older donors in aplastic anemia; thus, donor age should be considered when multiple donors are available. A large-scale prospective study is warranted to establish a better donor selection algorithm for bone marrow transplantation in aplastic anemia. PMID:26858357

  8. Systemic and Local Administration of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells Promotes Fracture Healing in Rats.

    PubMed

    Huang, Shuo; Xu, Liangliang; Zhang, Yifeng; Sun, Yuxin; Li, Gang

    2015-01-01

    Mesenchymal stem cells (MSCs) are immune privileged and a cell source for tissue repair. Previous studies showed that there is systemic mobilization of osteoblastic precursors to the fracture site. We hypothesized that both systemic and local administration of allogeneic MSCs may promote fracture healing. Bone marrow-derived MSCs and skin fibroblasts were isolated from GFP Sprague-Dawley rats, cultured, and characterized. Closed transverse femoral fracture with internal fixation was established in 48 adult male Sprague-Dawley rats, which were randomly assigned into four groups receiving PBS injection, MSC systemic injection, fibroblast systemic injection, and MSC fracture site injection; 2 × 10(6) cells were injected at 4 days after fracture. All animals were sacrificed at 5 weeks after fracture; examinations included weekly radiograph, micro-CT, mechanical testing, histology, immunohistochemistry, and double immunofluorescence. The callus size of MSC injection groups was significantly larger among all the groups. Radiographs and 3D reconstruction images showed that the fracture gaps united in the MSC injected groups, while gaps were still seen in the fibroblast and PBS injection groups. The mechanical properties were significantly higher in the MSC injection groups than those in the fibroblast and PBS groups, but no difference was found between the MSC local and systemic injection groups. Immunohistochemistry and double immunofluorescence demonstrated that GFP-positive MSCs were present in the callus in the MSC injection groups at 5 weeks after fracture, and some differentiated into osteoblasts. Quantitative analysis revealed the number of GFP-positive cells in the callus in the MSC systemic injection group was significantly lower than that of the MSC local injection group. The proportion of GFP osteoblasts in GFP-positive cells in the MSC systemic injection group was significantly lower than that of the MSC local injection group. These findings provide critical

  9. Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation

    PubMed Central

    Nevruz, Oral; Avcu, Ferit; Ural, A. Uğur; Pekel, Aysel; Dirican, Bahar; Safalı, Mükerrem; Akdağ, Elvin; Beyzadeoğlu, Murat; İde, Tayfun; Sengül, Ali

    2013-01-01

    Objective: Graft-versus-host disease (GVHD) is a major obstacle to successful allogeneic bone marrow transplantation (allo-BMT). While multipotent mesenchymal stromal cells (MSCs) demonstrate alloresponse in vitro and in vivo, they also have clinical applications toward prevention or treatment of GVHD. The aim of this study was to investigate the ability of MSCs to prevent or treat GVHD in a rat BMT model. Materials and Methods: The GVHD model was established by transplantation of Sprague Dawley rats’ bone marrow and spleen cells into lethally irradiated (950 cGy) SDxWistar rat recipients. A total of 49 rats were randomly assigned to 4 study and 3 control groups administered different GVHD prophylactic regimens including MSCs. After transplantation, clinical GVHD scores and survival status were monitored. Results: All irradiated and untreated control mice with GVHD died. MSCs inhibited lethal GVHD as efficiently as the standard GVHD prophylactic regimen. The gross and histopathological findings of GVHD and the ratio of CD4/CD8 expression decreased. The subgroup given MSCs displayed higher in vivo proportions of CD25+ T cells and plasma interleukin-2 levels as compared to conventional GVHD treatment after allo-BMT. Conclusion: Our results suggest that clinical use of MSCs in both prophylaxis against and treatment of established GVHD is effective. This study supports the use of MSCs in the prophylaxis and treatment of GVHD after allo-BMT; however, large scale studies are needed. Conflict of interest:None declared. PMID:24385804

  10. Reduction and repopulation of recipient T4+ and T8+ T-lymphocytes in allogeneic bone marrow transplantation

    SciTech Connect

    Gratama, J.W.; van den Bergh, R.L.; Naipal, A.; D'Amaro, J.; Zwaan, F.E.; Jansen, J.; de Gast, G.C.

    1986-02-01

    In eight recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repopulation of T4+ and T8+ T-lymphocytes of recipient origin were studied. The origin of the donor-recipient T4+ and T8+ T cells was studied using quinacrine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of five (range 1-8) days after BMT. T8+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells that appeared in the circulation at day 12 were predominantly T4+, and a large number of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection.

  11. Pre-treatment of allogeneic bone marrow recipients with the CXCR4 antagonist AMD3100 transiently enhances hematopoietic chimerism without promoting donor-specific skin allograft tolerance.

    PubMed

    Li, Zhanzhuo; Xu, Xin; Weiss, Ido D; Jacobson, Orit; Murphy, Philip M

    2015-10-01

    Hematopoietic chimerism established by allogeneic bone marrow transplantation is known to promote donor-specific organ allograft tolerance; however, clinical application is limited by the need for toxic host conditioning and "megadoses" of donor bone marrow cells. A potential solution to this problem has been suggested by the observation that recipient bone marrow mobilization by the CXCR4 antagonist AMD3100 promotes chimerism in congenic bone marrow transplantation experiments in mice. Here we report that a single subcutaneous dose of 10 mg/kg AMD3100 in recipient C57BL/6 mice was able to enhance hematopoietic chimerism when complete MHC-mismatched BALB/c donor bone marrow cells were transplanted 1h after drug dosing. However, levels of chimerism measured 30 days post-transplantation were not sustained when mice were reexamined on day 90 post-transplantation. Moreover, transient chimerism induced by this protocol did not support robust donor-specific skin allograft tolerance. Using the same transient immunosuppression protocol, we confirmed that "megadoses" of donor bone marrow cells could induce durable chimerism associated with donor-specific skin allograft tolerance without AMD3100 pre-treatment. We conclude that in this protocol AMD3100 pretreatment may empty bone marrow niches that become reoccupied by allogeneic donor hematopoietic progenitor cells but not by true long-lived donor hematopoietic stem cells, resulting in short-lived chimerism and failure to support durable donor-specific allograft tolerance.

  12. A comparison of commercially available demineralized bone matrices with and without human mesenchymal stem cells in a rodent spinal fusion model.

    PubMed

    Hayashi, Tetsuo; Lord, Elizabeth L; Suzuki, Akinobu; Takahashi, Shinji; Scott, Trevor P; Phan, Kevin; Tian, Haijun; Daubs, Michael D; Shiba, Keiichiro; Wang, Jeffrey C

    2016-07-01

    OBJECTIVE The efficacy of some demineralized bone matrix (DBM) substances has been demonstrated in the spinal fusion of rats; however, no previous comparative study has reported the efficacy of DBM with human mesenchymal stem cells (hMSCs). There is an added cost to the products with stem cells, which should be justified by improved osteogenic potential. The purpose of this study is to prospectively compare the fusion rates of 3 different commercially available DBM substances, both with and without hMSCs. METHODS Posterolateral fusion was performed in 32 mature athymic nude rats. Three groups of 8 rats were implanted with 1 of 3 DBMs: Trinity Evolution (DBM with stem cells), Grafton (DBM without stem cells), or DBX (DBM without stem cells). A fourth group with no implanted material was used as a control group. Radiographs were obtained at 2, 4, and 8 weeks. The rats were euthanized at 8 weeks. Overall fusion was determined by manual palpation and micro-CT. RESULTS The fusion rates at 8 weeks on the radiographs for Trinity Evolution, Grafton, and DBX were 8 of 8 rats, 3 of 8 rats, and 5 of 8 rats, respectively. A significant difference was found between Trinity Evolution and Grafton (p = 0.01). The overall fusion rates as determined by micro-CT and manual palpation for Trinity Evolution, Grafton, and DBX were 4 of 8 rats, 3 of 8 rats, and 3 of 8 rats, respectively. The Trinity Evolution substance had the highest overall fusion rate, however no significant difference was found between groups. CONCLUSIONS The efficacies of these DBM substances are demonstrated; however, the advantage of DBM with hMSCs could not be found in terms of posterolateral fusion. When evaluating spinal fusion using DBM substances, CT analysis is necessary in order to not overestimate fusion.

  13. Potential of centrifugal seeding method in improving cells distribution and proliferation on demineralized cancellous bone scaffolds for tissue-engineered meniscus.

    PubMed

    Zhang, Zheng-Zheng; Jiang, Dong; Wang, Shao-Jie; Qi, Yan-Song; Zhang, Ji-Ying; Yu, Jia-Kuo

    2015-07-22

    Tissue-engineered meniscus offers a possible solution to the regeneration and replacement problem of meniscectomy. However, the nonuniform distribution and declined proliferation of seeded cells on scaffolds hinder the application of tissue-engineered meniscus as a new generation of meniscus graft. This study systematically investigated the performances of different seeding techniques by using the demineralized cancellous bone (DCB) as the scaffold. Static seeding, injection seeding, centrifugal seeding, and vacuum seeding methods were used to seed the meniscal fibrochondrocytes (MFCs) and mesenchymal stem cells (MSCs) to scaffolds. Cell-binding efficiency, survival rate, distribution ability, and long-term proliferation effects on scaffolds were quantitatively evaluated. Cell adhesion was compared via cell-binding kinetics. Cell viability and morphology were assessed by using fluorescence staining. Combined with the reconstructed three-dimensional image, the distribution of seeded cells was investigated. The Cell Counting Kit-8 assay and DNA assay were employed to assess cell proliferation. Cell-binding kinetics and cell survival of the MFCs were improved via centrifugal seeding compared to injection or vacuum seeding methods. Seeded MFCs by centrifugation showed a more homogeneous distribution throughout the scaffold than cells seeded by other methods. Moreover, the penetration depth in the scaffold of seeded MFCs by centrifugation was 300-500 μm, much higher than the value of 100-300 μm by the surface static and injection seeding. The long-term proliferation of the MFCs in the centrifugal group was also significantly higher than that in the other groups. The results of the MSCs were similar to those of the MFCs. The centrifugal seeding method could significantly improve MFCs or MSCs distribution and proliferation on the DCB scaffolds, thus providing a simple, cost-effective, and effective cell-seeding protocol for tissue-engineered meniscus.

  14. A clinical and radiological evaluation of the relative efficacy of demineralized freeze-dried bone allograft versus anorganic bovine bone xenograft in the treatment of human infrabony periodontal defects: A 6 months follow-up study

    PubMed Central

    Blaggana, Vikram; Gill, Amarjit Singh; Blaggana, Anshu

    2014-01-01

    Background: The ultimate goal of periodontal therapy entails regeneration of the periodontal tissues lost as a consequence of periodontitis. Predictable correction of vertical osseous defects has however posed as a constant therapeutic challenge. The aim of our present study is to evaluate the relative efficacy of demineralized freeze-dried bone allograft (DFDBA) vs anorganic bovine bone xenograft (ABBX) in the treatment of human infrabony periodontal defects. Materials and Methods: 15 patients with 30 bilaterally symmetrical defect sites in either of the arches, in the age group of 25-50 years were selected as part of split-mouth study design. Defect-A (right side) was grafted with DFDBA while Defect-B (left side) was grafted with ABBX. Various clinical and radiographic parameters viz. probing depth(PD), clinical attachment level(CAL) and linear bone fill were recorded preoperatively, 12- & 24-weeks postoperatively. Results: Both defect-A & defect-B sites exhibited a highly significant reduction in probing depth, and gain in clinical attachment level and linear bone fill at 12-weeks & at the end of 24-weeks. Comparative evaluation between the study groups revealed a statistically non-significant reduction in probing depth (P<0.1) and mean gain in linear bone fill (P<0.1). However, there was a statistically significant gain in clinical attachment level (P<0.05) in Defect-A (CD=0.356) as compared to Defect-B (CD=0.346). Conclusions: Within the limits of this study, both the materials viz. ABBX and DFDBA are beneficial for the treatment of periodontal infrabony defects. Both the materials were found to be equally effective in all respects except the gain in attachment level, which was found to be more with DFDBA. Long-term studies are suggested to evaluate further the relative efficacy of the two grafts. PMID:25425822

  15. Interleukin-1 administration before lethal irradiation and allogeneic bone marrow transplantation: early transient increase of peripheral granulocytes and successful engraftment with accelerated leukocyte, erythrocyte, and platelet recovery.

    PubMed

    Tiberghien, P; Laithier, V; Mabed, M; Racadot, E; Reynolds, C W; Angonin, R; Loumi, R; Pavy, J J; Cahn, J Y; Noir, A

    1993-04-01

    Administration of interleukin-1 beta (IL-1 beta) before a lethal irradiation with or without allogeneic bone marrow transplantation (BMT) protects greater than 90% of the irradiated mice. To approach the mechanisms responsible for the radioprotective effect of IL-1, we examined the effects of IL-1 pretreatment on engraftment and kinetics of peripheral blood, spleen, and marrow cell reconstitution after irradiation and BMT. Although the BMT was not necessary for the survival of the IL-1-pretreated lethally irradiated mice, allogeneic marrow did engraft in these mice as evaluated in the spleen and marrow 2 months after BMT. IL-1 pretreatment significantly accelerated hematopoietic recovery versus transplanted saline-treated controls with a pronounced enhancement of peripheral leukocyte, platelet, and erythrocyte recovery. Leukocyte recovery in IL-1-pretreated mice was unique in that IL-1 first induced an early transient (maximum at day 7) increase of peripheral granulocytes before accelerating leukocyte recovery after day 11. IL-1 pretreatment also significantly enhanced marrow cell recovery after allogeneic BMT with an eightfold increase in marrow cellularity from day 4 to 11 versus control transplanted mice. When lethal irradiation was not followed by allogeneic BMT. IL-1 pretreatment also affected the peripheral reconstitution of leukocytes, platelets, and erythrocytes. Interestingly, in the absence of BMT, IL-1 also induced an early circulation of peripheral granulocytes. Overall, our data demonstrate that a single administration of IL-1 before lethal irradiation and allogeneic BMT can induce an early transient increase of circulating granulocytes, followed by an accelerated multilineage recovery and long-term allogeneic engraftment. PMID:8461477

  16. The triterpenoid CDDO-Me delays murine acute graft-versus-host disease with the preservation of graft-versus-tumor effects after allogeneic bone marrow transplantation

    PubMed Central

    Li, Minghui; Sun, Kai; Redelman, Doug; Welniak, Lisbeth A.; Murphy, William J.

    2010-01-01

    The occurrence of acute graft-versus-host disease (GVHD) and tumor relapse represent the two major obstacles impeding the efficacy of allogeneic bone marrow transplantation (BMT) in cancer. We have previously shown that the synthetic triterpenoid CDDO can inhibit murine early acute GVHD but anti-tumor effects were not assessed. In the current study, we found that a new derivative of CDDO, CDDO-Me, had an increased ability to inhibit allogeneic T cell responses and induce cell death of alloreactive T cells in vitro. Administration of CDDO-Me to mice following allogeneic BMT resulted in significant and increased protection from acute lethal GVHD compared to CDDO. This correlated with reduced TNF-α production, reduced donor T cell proliferation and decreased adhesion molecule (α4β7 integrin) expression on the donor T cells. CDDO-Me was also superior to CDDO in inhibiting leukemia growth in vitro. When CDDO-Me was administered following an allogeneic BMT to leukemia-bearing mice, significant increases in survival were observed. These findings suggest that CDDO-Me is superior to CDDO in delaying acute GVHD while preserving or possibly even augmenting GVT effects. PMID:20338256

  17. [Detection of mixed lymphoid chimerism after allogeneic bone marrow transplantation: demonstration by interphase cytogenetics in paraffin-embedded tissue].

    PubMed

    Friedrich, T; Ott, G; Kalla, J; Helbig, W; Schwenke, H; Kubel, M; Pönisch, W; Feyer, P; Friedrich, A

    1994-01-01

    In bone marrow transplantation (BMT) the detection of residual host lymphoid or haematopoietic cells surviving conditioning therapy is because of its association to graft-versus-host disease, graft-versus-leukemia reaction, and relapse of leukemia a matter of great interest. We studied the occurrence of this mixed lymphoid chimerism (MC) in the formol-fixed lymphatic tissue of lymph nodes and spleen from 21 autopsies after allogeneic sex-mismatched BMT (5 females, 16 males, survival 5 to 1140 days after BMT). In situ hybridisation with biotinylated centromer-specific anti-X- and anti-Y-chromosome probes was performed on pepsin-digested paraffin sections. The number of double X-, single X-, and Y-chromosome bearing cells was analysed microscopically. Because of artefacts only 14 cases remained for valid investigation. MC was detected in 6 cases (5 out of 11 males 5 days to 840 days and 1 out of 3 females 76 days after BMT). MC occurred after whole body irradiation with 10 Gy (n = 5) and 7 Gy (n = 1). In 1 autopsy relapse of leukemia caused host cell infiltration. Cases with MC did not express histological signs of acute or chronic graft-versus-host disease, but 5 out of 8 with complete lymphoid chimerism did. The sensitivity of interphase cytogenetics on paraffin embedded tissue is low.

  18. Factors influencing the late phase of recovery after bone mineral density loss in allogeneic stem cell transplantation survivors.

    PubMed

    Anandi, P; Jain, N A; Tian, X; Wu, C O; Pophali, P A; Koklanaris, E; Ito, S; Savani, B N; Barrett, J; Battiwalla, M

    2016-08-01

    Accelerated bone mineral density loss (BMDL) occurs early after allogeneic stem cell transplantation (SCT) and is related to factors such as steroids and chronic GvHD. In order to understand the natural history of BMDL of SCT in the longer term, we evaluated a longitudinal cohort of 148 survivors with a median follow-up of 12 years (range 3-22 years). All women received hormone replacement therapy, and routine calcium/vitamin D supplementation was recommended but ∼50% of patients still had suboptimal vitamin D levels and bisphosphonates were rarely utilized. BMD significantly improved from 5 to 20+ years but the femoral neck and forearm remained vulnerable sites. Younger age, higher pretransplant body mass index (BMI) and increment in BMI post transplant were significantly associated with increased BMD and protected against osteopenia/osteoporosis. These findings support consideration of BMD loss in SCT survivors in two phases, an early phase of BMD loss (3-5 years) followed by a later phase of BMD recovery, with different protective and aggravating factors. Treatment- and transplant-related factors (such as steroids, immunosuppressives, chronic GvHD, vitamin D) are known to impact the early phase of BMD loss but age and BMI are more influential in the late phase of BMD recovery. PMID:27042843

  19. Two-level contiguous cervical disc disease treated with peek cages packed with demineralized bone matrix: results of 3-year follow-up

    PubMed Central

    Topuz, Kıvanç; Çolak, Ahmet; Şimşek, Hakan; Kutlay, Murat; Demircan, Mehmet Nusret; Velioğlu, Murat

    2009-01-01

    Interbody cages are widely used instruments for cervical fusion operations. Long-term follow-up studies are needed to clarify if these devices are dependable. In this prospective study, 79 patients (42 women and 37 men) with a mean age of 51 years operated between January 2000 and December 2005 for treatment of degenerative cervical disc disease and spondylosis associated with radiculopathy or myelopathy were evaluated. Patients underwent two-level contiguous anterior cervical discectomy and fusion operations with standard anterior Smith–Robinson approach. To achieve fusion PEEK cages packed with demineralized bone matrix mixed with autologous blood were used. Clinical outcome was evaluated with Odom’s criteria and results were evaluated as ‘excellent’, ‘good’, ‘fair’ and ‘poor’. Spinal curves, mobility and fusion status were assessed with anterior–posterior and lateral (neutral, flexion and extension) radiographs obtained before surgery and at 3, 12, 24 and 36 months postoperatively. The Ishihara curvature index (ICI) was used for spinal curve evaluation. Lateral dynamic (flexion and extension) radiographs at postoperative 12th month revealed the fusion status classified as 1A, 1B, 2A and 2B. The radiological outcomes were classified as ‘non-fusion’ when 2B healing was observed, and as ‘fusion’ when 1A, 1B or 2A healing was observed at the levels subjected to surgery. According to Odom’s criteria, clinical outcomes were classified as ‘excellent’ or ‘good’ in 69 patients (success rate: 87.3%). Eight patients were graded as ‘fair’ and two as ‘poor’. Preoperative mean ICI was 10.4 ± 3.72 and postoperative mean ICI was 10.1 ± 3.14. The difference was statistically insignificant (P > 0.05); therefore, preoperative lordosis was said to be preserved at final follow-up. Final fusion rate (Types 1A, 1B, and 2A) was 91.7% (145/158 levels). Radiological imaging showed no cage failure or dislodgement and reoperation

  20. Numerical impairment of nestin(+) bone marrow niches in acute GvHD after allogeneic hematopoietic stem cell transplantation for AML.

    PubMed

    Medinger, M; Krenger, W; Jakab, A; Halter, J; Buser, A; Bucher, C; Passweg, J; Tzankov, A

    2015-11-01

    The nestin(+) perivascular bone marrow (BM) stem cell niche (N(+)SCN) may be involved in GvHD. To investigate whether acute GvHD (aGvHD) reduces the number of N(+)SCN, we examined patients with AML who had undergone allogeneic hematopoietic stem cell transplantation. In the test cohort (n=8), the number of N(+)SCN per mm(2) in BM biopsies was significantly reduced in aGvHD patients at the time of aGvHD compared with patients who did not have aGvHD (1.2±0.78 versus 2.6±0.93, P=0.04). In the validation cohort (n=40), the number of N(+)SCN was reduced (1.9±0.99 versus 2.6±0.90 N(+)SCN/mm(2), P=0.05) in aGvHD patients. Receiver operating curves suggested that the cutoff score that best discriminated between patients with and without aGvHD was 2.29 N(+)SCN/mm(2). Applying this cutoff score, 9/11 patients with clinically relevant aGvHD (⩾grade 2) and 13/20 with any type of GvHD had decreased N(+)SCN numbers compared with only 10/29 patients without clinically relevant aGvHD (P=0.007) and 6/20 patients without any type of GvHD (P=0.028). In patients tracked over time, N(+)SCN density returned to normal after aGvHD resolved or remained stable in patients who did not have aGvHD. Our results show a decrease in the number of N(+)SCN in aGvHD.

  1. Prostaglandin E2 Production and T Cell Function in Mouse Adenovirus Type 1 Infection following Allogeneic Bone Marrow Transplantation

    PubMed Central

    McCarthy, Mary K.; Procario, Megan C.; Wilke, Carol A.; Moore, Bethany B.; Weinberg, Jason B.

    2015-01-01

    Adenovirus infections are important complications of bone marrow transplantation (BMT). We demonstrate delayed clearance of mouse adenovirus type 1 (MAV-1) from lungs of mice following allogeneic BMT. Virus-induced prostaglandin E2 (PGE2) production was greater in BMT mice than in untransplanted controls, but BMT using PGE2-deficient donors or recipients failed to improve viral clearance, and treatment of untransplanted mice with the PGE2 analog misoprostol did not affect virus clearance. Lymphocyte recruitment to the lungs was not significantly affected by BMT. Intracellular cytokine staining of lung lymphocytes demonstrated impaired production of INF-γ and granzyme B by cells from BMT mice, and production of IFN-γ, IL-2, IL-4, and IL-17 following ex vivo stimulation was impaired in lymphocytes obtained from lungs of BMT mice. Viral clearance was not delayed in untransplanted INF-γ-deficient mice, suggesting that delayed viral clearance in BMT mice was not a direct consequence of impaired IFN-γ production. However, lung viral loads were higher in untransplanted CD8-deficient mice than in controls, suggesting that delayed MAV-1 clearance in BMT mice is due to defective CD8 T cell function. We did not detect significant induction of IFN-β expression in lungs of BMT mice or untransplanted controls, and viral clearance was not delayed in untransplanted type I IFN-unresponsive mice. We conclude that PGE2 overproduction in BMT mice is not directly responsible for delayed viral clearance. PGE2-independent effects on CD8 T cell function likely contribute to the inability of BMT mice to clear MAV-1 from the lungs. PMID:26407316

  2. Specific allogeneic unresponsiveness in irradiated dogs reconstituted with autologous bone marrow. [/sup 60/Co

    SciTech Connect

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

    1980-07-01

    Hemopoietic reconstitution of supralethally irradiated adult dogs of the Cooperstown colony with their own stored bone marrow can produce long-term unresponsiveness to DLA-identical kidney allografts with no need for any additional immunosuppression. Eleven of 18 kidneys transplanted 12 h after replacement of autologous marrow into irradiated recipients currently survive with normal function for as long as 1417 d; 8 of 13 organs transplanted 28 h after marrow replacement, and 8 of 13 organs transplanted 36 h after marrow injection, currently survive up to 502 d, with no further treatment. Alterations in the timing and sequence of each procedure decrease the incidence of unresponsiveness. Survival and function of the kidney allografts were not affected by the rejection of successive skin grafts from the kidney donor. Skin grafts from other DLA-identical donors and DLA-incompatible skin grafts were rejected by the same recipients in uniform fashion.

  3. Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10. D2----B10)

    SciTech Connect

    Ildstad, S.T.; Wren, S.M.; Bluestone, J.A.; Barbieri, S.A.; Stephany, D.; Sachs, D.H.

    1986-01-01

    Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. Experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it.

  4. Suppression of lentivirus-mediated transgenic dendritic cells in graft-versus-host disease after allogeneic bone marrow transplantation in mice.

    PubMed

    Xu, Y J; Chen, W R; Li, D P; Song, L X; Wu, J Q; Zhang, P; Li, Z Y; Huang, Y H

    2015-01-01

    We determined whether genetically engineered immature dendritic cells (imDCs) mediated by lentiviral vectors alleviate acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) in mice. We introduced the mouse chemokine receptor 7 (Ccr7) gene into the bone marrow-derived imDCs of C57BL/6 mice to construct genetically engineered imDCs. A 1:1 mixture of bone marrow and spleen cells from the donors was injected into the recipients, which were divided into four groups: radiation, transplantation, empty vector, and transgenic imDC groups. Symptoms, clinical scores, GVHD pathological changes, and survival times and rates of recipients were recorded; secretion of IFN-γ and IL-4, and allogeneic chimerism rates were detected. The survival time of the transgenic imDC group (27.5 ± 7.55 days) was significantly longer than in the other three groups (P < 0.01). The GVHD score of the imDC group mice was significantly lower than in the transplantation and empty vector groups (P < 0.05), which meant that mice in the transgenic imDC group had the lightest pathology damage in the target organs. In the transplantation group, IFN-γ increased while IL-4 decreased. In contrast, IFN-γ decreased and IL-4 increased in both empty vector and trans-imDC groups, and the difference was significant in the latter (P < 0.01). Thirty days or more following transplantation, the allogeneic chimerism rate was still 95-100%, suggesting complete donor type implantation. Ccr7 transfection into imDCs suppressed occurrence and severity of acute GVHD after allo-BMT in mice; the mechanism might be associated with IFN-γ decrease and IL-4 increase. PMID:26436385

  5. Studies of allogeneic bone marrow and spleen cell transplantation in a murine model using ultraviolet-B light

    SciTech Connect

    Pamphilon, D.H.; Alnaqdy, A.A.; Godwin, V.; Preece, A.W.; Wallington, T.B. )

    1991-05-01

    Ultraviolet irradiation inhibits alloreactive and mitogen-induced responses and might reduce both graft-versus-host and host-versus-graft reactions after bone marrow transplantation (BMT). We have studied proliferative responses to mitogens and reactivity in mixed lymphocyte culture after irradiation with ultraviolet (UV)-B light using splenocytes from Balb/c (H-2d) and CBA (H-2k) mice. Response to mitogens and in MLC was strongly inhibited by 20 J/m{sup 2} and abolished at 50 J/m{sup 2}. Clonogenic cell recovery (CFU-GM; CFU-S) after UV-B irradiation was also reduced. When bone marrow and spleen cells were transplanted from parent (Balb/c) animals into F1 hybrid (Balb/c X CBA) recipients, all animals died with features indicative of graft-versus-host disease (GVHD) in 34 days. If the grafts were first irradiated with 100 J/m{sup 2} of UV-B at a mean wavelength of 310 nm, then 76% survived to day 80 when they were killed and shown to have normal marrow cellularity. The remainder died in marrow aplasia or of GVHD. H-2 typing in a group of surviving recipients showed either donor hematopoiesis only (8 of 15), mixed allogeneic chimerism (5 of 15), or recipient type hematopoiesis (2 of 15). Higher doses (200 to 300 J/m{sup 2}) were detrimental to survival with 88% of recipients dying in marrow aplasia. Syngeneic BMT in Balb/c mice showed slower hematopoietic reconstitution when the grafts were first irradiated with 100 J/m{sup 2}. After BMT from Balb/c to CBA mice all recipients of unirradiated grafts died within 54 days. By contrast, after graft irradiation with 100 J/m{sup 2} survival of recipient animals to day 80 was 59%. If these grafts were treated with 50 J/m{sup 2} survival was only 26% with an increase in deaths due to GVHD. Hematopoiesis at day 80 in a group of survivors studied by Ig heavy chain allotyping indicated donor type hematopoiesis in 6 of 10 (50 J/m{sup 2}) and 2 of 9 (100 J/m{sup 2}).

  6. T Cell Repertoire Development in XSCID Dogs Following Non-conditioned Allogeneic Bone Marrow Transplantation

    PubMed Central

    Vernau, William; Hartnett, Brian J.; Kennedy, Douglas R.; Moore, Peter F.; Henthorn, Paula S.; Weinberg, Kenneth I.; Felsburg, Peter J.

    2007-01-01

    Dogs with X-linked severe combined immunodeficiency (XSCID) can be successfully treated by bone marrow transplants (BMT) resulting in full immunologic reconstitution and engraftment of both donor B and T cells without the need for pre-transplant conditioning. In this study, we evaluated the T cell diversity in XSCID dogs 4 months to 10 1/2 years following BMT. At 4 months post transplantation, when the number of CD45RA+ (naïve) T cells had peaked and plateaued, the T cells in the transplanted dogs showed the same complex, diverse repertoire as those of normal young adult dogs. A decline in T cell diversity became evident approximately 3 1/2 years post transplant, but the proportion of Vβ families showing a polyclonal Gaussian spectratype still predominated up to 7 1/2 years post transplant. In two dogs evaluated at 7 1/2 and 10 1/2 years post transplant, >75% of the Vβ families consisted of a skewed or oligoclonal spectratype that was associated with a CD4/CD8 ratio of <0.5. The decline in the complexity of T cell diversity in the transplanted XSCID dogs is similar to that reported for XSCID patients following BMT. However, in contrast to transplanted XSCID boys who show a significant decline in their T cell diversity by 10 to 12 years following BMT, transplanted XSCID dogs maintain a polyclonal, diverse T cell repertoire through mid-life. PMID:17697962

  7. Effect of body mass in children with hematologic malignancies undergoing allogeneic bone marrow transplantation

    PubMed Central

    Aplenc, Richard; Zhang, Mei-Jie; Sung, Lillian; Zhu, Xiaochun; Ho, Vincent T.; Cooke, Kenneth; Dvorak, Christopher; Hale, Gregory; Isola, Luis M.; Lazarus, Hillard M.; McCarthy, Philip L.; Olsson, Richard; Pulsipher, Michael; Bunin, Nancy

    2014-01-01

    The rising incidence of pediatric obesity may significantly affect bone marrow transplantation (BMT) outcomes. We analyzed outcomes in 3687 children worldwide who received cyclophosphamide-based BMT regimens for leukemias between 1990 and 2007. Recipients were classified according to age-adjusted body mass index (BMI) percentiles as underweight (UW), at risk of UW (RUW), normal, overweight (OW), or obese (OB). Median age and race were similar in all groups. Sixty-one percent of OB children were from the United States/Canada. Three-year relapse-free and overall survival ranged from 48% to 52% (P = .54) and 55% to 58% (P = .81) across BMI groups. Three-year leukemia relapses were 33%, 33%, 29%, 25%, and 21% in the UW, RUW, normal, OW, and OB groups, respectively (P < .001). Corresponding cumulative incidences for transplant-related mortality (TRM) were 18%, 19%, 21%, 22%, and 28% (P < .01). Multivariate analysis demonstrated a decreased risk of relapse compared with normal BMI (relative risk [RR] = 0.73; P < .01) and a trend toward higher TRM (RR = 1.28; P = .014). BMI in children is not significantly associated with different survival after BMT for hematologic malignancies. Obese children experience less relapse posttransplant compared with children with normal BMI; however, this benefit is offset by excess in TRM. PMID:24711663

  8. Characterization of plasma cell populations at autopsy after human allogeneic bone marrow transplantation.

    PubMed Central

    Cousineau, S.; Belanger, R.; Perreault, C.

    1986-01-01

    Postmortem fixed tissue sections of the lymphoid and digestive systems of eight consecutive leukemic patients dying of various diseases after bone marrow transplantation (BMT) were analyzed for the presence of the heavy chains gamma, alpha, mu, delta, and epsilon and light chains kappa and lambda, with the use of a standard immunoperoxidase method. Two distinct types of plasma cell populations were found. The first type was a widely distributed polyclonal plasma cell population, lacking IgD-positive plasma cells and germinal centers. The second type of plasma cell population, found in 6 of 8 patients, was a group of monoclonal plasma cell populations positive for the heavy chains gamma, alpha, mu, or delta. Recent immunohistologic observations of the human lymph node suggest that the first type of polyclonal plasma cell population could arise from a nonspecific expansion of sIgM+, sIgD- B lymphocytes. The lack of germinal centers, a structure closely involved in specific-antibody production, may correlate with the poor specific-antibody response documented in patients after BMT. The monoclonal plasma cell populations, found with an unexpectedly high frequency, are probably related to a functional T-cell defect. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3089020

  9. Chimaerism of immunocompetent cells in allogeneic bone marrow-reconstituted lethally irradiated chickens.

    PubMed

    Lydyard, P M; Ivanvi, J

    1975-08-01

    Injection of parental bone marrow cells into 12-day-old lethally irradiated F1 hybrid chickens resulted in chimaerism of donor-type graft-versus-host (GVH)-reactive cells and suppression of antisheep red blood cell antibody response. These manifestations of a chronic graft-versus-host reaction were prevented by pretreatment of the donor marrow with specific anti-T cell globulin. In some chimaeras donor-type GVH-reactive cells developed gradually from T cells precursors of donor origin. Transplantation of spleen and marrow cells from sheep red blood cell-primed F1 hybrid donors into lethally irradiated parental recipients resulted in the loss of memory potential within 1-2 weeks of transfer, whereas donor-type IgG allotype synthesis was preserved. Injection of goat antichicken thymocyte serum to recipients 1 day before reconstitution enabled the antibody response of memory cells at 1-2 weeks, although it failed to prevent their rejection by 8-9 weeeks after transplantation. Split chimaerism of donor-type GVH-reactive cells was demonstrated in chickens which had previously rejected the B cells derived from the same graft. PMID:241144

  10. Amalgamation of allogenic bone graft, platelet-rich fibrin gel, and PRF membrane in auto-transplantation of an impacted central incisor.

    PubMed

    Chaudhary, Zainab; Kumar, Yuvika Raj; Mohanty, Sujata; Khetrapal, Ambica

    2015-01-01

    "Social six" teeth refers to the maxillary incisors and canines that play a vital role in the appearance of an individual and absence of any one of them has a significant psycho-social impact. Hence, early treatment and rehabilitation of the same are extremely important. A multitude of treatment options ranging from orthodontic extrusion, extraction followed by implant placement, fixed partial denture, and auto-transplantation have been advocated. This case report discusses the unique amalgamation of platelet-rich fibrin (PRF), demineralized freeze-dried bone graft with use of PRF membrane during auto-transplantation of an impacted central incisor. The authors have focused on maximum usage of autogenous materials in the most economic and least invasive manner. Furthermore, this amalgamation has been used to provide rehabilitation in the least span of time.

  11. Amalgamation of allogenic bone graft, platelet-rich fibrin gel, and PRF membrane in auto-transplantation of an impacted central incisor

    PubMed Central

    Chaudhary, Zainab; Kumar, Yuvika Raj; Mohanty, Sujata; Khetrapal, Ambica

    2015-01-01

    “Social six” teeth refers to the maxillary incisors and canines that play a vital role in the appearance of an individual and absence of any one of them has a significant psycho-social impact. Hence, early treatment and rehabilitation of the same are extremely important. A multitude of treatment options ranging from orthodontic extrusion, extraction followed by implant placement, fixed partial denture, and auto-transplantation have been advocated. This case report discusses the unique amalgamation of platelet-rich fibrin (PRF), demineralized freeze-dried bone graft with use of PRF membrane during auto-transplantation of an impacted central incisor. The authors have focused on maximum usage of autogenous materials in the most economic and least invasive manner. Furthermore, this amalgamation has been used to provide rehabilitation in the least span of time. PMID:26097366

  12. Long-term effects of allogeneic bone marrow transplantation (BMT) on pituitary, gonad, thyroid and adrenal function in adults.

    PubMed

    Kauppila, M; Koskinen, P; Irjala, K; Remes, K; Viikari, J

    1998-08-01

    To evaluate the late-effects of allogeneic bone marrow transplantation (BMT) on endocrine function 20 adults (10 females, 10 males) with hematological malignancies were studied after a mean of 3.2 years (range 1.0-10.0) following BMT. The mean age of patients at the time of BMT was 39 years. Dynamic tests of the hypothalamic-pituitary axis included growth hormone releasing hormone (GHRH), gonadotropin releasing hormone (GnRH) and thyrotropin releasing hormone (TRH) stimulations with measurements of serum growth hormone (GH), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyrotropin (TSH) and prolactin (PRL) responses. Adrenal function was assessed with the adrenocorticotropin (ACTH) test. Five patients (25%) had a subnormal GH response to GHRH stimulation, but all had a normal serum insulin-like growth factor I (IGF-I) value. There was an inverse nonlinear relationship between the body mass index (BMI; kg/m2) and GH response but no relation between the GH response and total body irradiation (TBI), intrathecal treatment or occurrence of graft-versus-host disease. In females, serum FSH and LH basal levels and responses to GnRH, in spite of oestrogen substitution therapy in 9/10 patients, indicated ovarian failure and early menopause. Most responses to GnRH were delayed. All males had elevated serum basal FSH levels indicating damage in seminiferous tubulus and infertility. Serum basal LH was elevated only in four males but testosterone values were all within normal limits. However, the mean free androgen index (FAI) was in the low normal range, and two subjects had abnormally low FAI. Serum free thyroxine (fT4) levels were normal in all but one, but an exaggerated TSH response to TRH occurred in seven patients (35%). Four of them had received TBI and one total nodal irradiation suggesting radiation-induced damage to the thyroid gland. In 19 of the 20 patients, adrenal function judged with ACTH test was normal. We conclude that functional impairments

  13. 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; Umbilical ...

  14. In vitro cartilage tissue engineering using cancellous bone matrix gelatin as a biodegradable scaffold.

    PubMed

    Yang, Bo; Yin, Zhanhai; Cao, Junling; Shi, Zhongli; Zhang, Zengtie; Song, Hongxing; Liu, Fuqiang; Caterson, Bruce

    2010-08-01

    In this study, we constructed tissue-engineered cartilage using allogeneic cancellous bone matrix gelatin (BMG) as a scaffold. Allogeneic BMG was prepared by sequential defatting, demineralization and denaturation. Isolated rabbit chondrocytes were seeded onto allogeneic cancellous BMG, and cell-BMG constructs were harvested after 1, 3 and 6 weeks for evaluation by hematoxylin and eosin staining for overall morphology, toluidine blue for extracellular matrix (ECM) proteoglycans, immunohistochemical staining for collagen type II and a transmission electron microscope for examining cellular microstructure on BMG. The prepared BMG was highly porous with mechanical strength adjustable by duration of demineralization and was easily trimmed for tissue repair. Cancellous BMG showed favorable porosity for cell habitation and metabolism material exchange with larger pore sizes (100-500 microm) than in cortical BMG (5-15 microm), allowing cell penetration. Cancellous BMG also showed good biocompatibility, which supported chondrocyte proliferation and sustained their differentiated phenotype in culture for up to 6 weeks. Rich and evenly distributed cartilage ECM proteoglycans and collagen type II were observed around chondrocytes on the surface and inside the pores throughout the cancellous BMG. Considering the large supply of banked bone allografts and relatively convenient preparation, our study suggests that allogeneic cancellous BMG is a promising scaffold for cartilage tissue engineering.

  15. Human interleukin 1. beta. (IL-1. beta. ), a more powerful inducer of bone demineralization than interleukin 1. cap alpha. IL-1. cap alpha. ), parathyroid hormone (PTH) or prostaglandin E/sub 2/ (PGE/sub 2/) in vitro

    SciTech Connect

    Chin, R.C.; Hodges, Y.C.; Allison, A.C.

    1986-03-01

    Effects of human IL-1..cap alpha.. and IL-1..beta.., prepared by recombinant DNA technology on cultures of rat fetal long bones, prelabelled with /sup 45/Ca were studied. IL-1..beta.. was found to be the most powerful inducer of bone calcium loss so far known. Maximal activity (2.5 times the control rate of calcium loss) was induced by IL-1..beta.. at concentrations between 1 x 10/sup -10/ M to 6 x 10/sup -12/ M. With IL-1..cap alpha.. maximal activity (1.5 times the control rate of calcium loss) was obtained at 6 x 10/sup -10/ M. With bovine PTH (1-34) maximal activity (1.8 times the control rate of calcium loss) was obtained at 1 x 10/sup -8/ M. With PGE/sub 2/ maximal activity (1.6 times the control rate of calcium loss) was obtained at 1 x 10/sup -7/ M. The calcium loss induced by IL-1..beta.. was inhibited in the presence of 1 x 10/sup -7/ M indomethacin, 5 x 10/sup -5/ M naproxen or ketorolac, or 5 x 10/sup -6/ M cyclohexamide. These findings suggest that protein synthesis and prostaglandin formation are required to mediate bone demineralization induced by IL-1..beta...

  16. Effects of T cell depletion in radiation bone marrow chimeras. I. Evidence for a donor cell population which increases allogeneic chimerism but which lacks the potential to produce GVHD

    SciTech Connect

    Sykes, M.; Sheard, M.; Sachs, D.H.

    1988-10-01

    The opposing problems of graft-vs-host disease (GVHD) and failure of alloengraftment present major obstacles to the application of bone marrow transplantation (BMT) across complete MHC barriers. The addition of syngeneic T-cell-depleted (TCD) bone marrow (BM) to untreated fully allogeneic marrow inocula in lethally irradiated mice has been previously shown to provide protection from GVHD. We have used this model to study the effects of allogeneic T cells on levels of chimerism in recipients of mixed marrow inocula. The results indicate that T cells in allogeneic BM inocula eliminate both coadministered recipient-strain and radioresistant host hematopoietic elements to produce complete allogeneic chimerism without clinical GVHD. To determine the role of GVH reactivity in this phenomenon, we performed similar studies in an F1 into parent combination, in which the genetic potential for GVHD is lacking. The presence of T cells in F1 marrow inocula led to predominant repopulation with F1 lymphocytes in such chimeras, even when coadministered with TCD-recipient-strain BM. These results imply that the ability of allogeneic BM cells removed by T cell depletion to increase levels of allochimerism may be mediated by a population which is distinct from that which produces GVHD. These results may have implications for clinical BM transplantation.

  17. Efficient natural defense mechanisms against Listeria monocytogenes in T and B cell-deficient allogeneic bone marrow radiation chimeras. Preactivated macrophages are the main effector cells in an early phase after bone marrow transfer

    SciTech Connect

    Roesler, J.; Groettrup, E.B.; Baccarini, M.; Lohmann-Mattes, M.L. )

    1989-09-01

    Radiation chimeras in the early phase after bone marrow transplantation are a good model to study the efficiency of the body's nonspecific defense system represented by macrophages (M phi), polymorphonuclear cells (PMN), and NK cells. These cell types are present in large numbers in spleen and liver at that time, whereas the specific immune system represented by T and B cells is functionally deficient. We previously reported enhanced activities in vitro of M phi (and PMN) from recipient animals in an early phase after allogeneic bone marrow transfer. We here demonstrate that these activities result in enhanced spontaneous resistance against Listeria monocytogenes in vivo: CFU of L. monocytogenes in spleen and liver 48 h after infection were about 1 or 2 to 4 log steps less than in untreated control mice of donor or host haplotype. This enhanced resistance decreased over the 4-mo period after marrow transfer. Preactivated M phi were identified as the most important effector cells. Isolated from spleen and peritoneal cavity, they performed enhanced killing of phagocytosed Listeria. Such preactivated M phi occurred in recipient animals after transfer of allogeneic but not of syngeneic bone marrow. The precise mechanism of M phi activation in the allogeneic radiation chimera in the complete absence of any detectable T cell function is not clear at present. However, these preactivated M phi display an important protective effect against L. monocytogenes: chimeras could eliminate Listeria without acquisition of positive delayed-type sensitivity when infected with 10(3) bacteria. An inoculum of 5 . 10(3) L. monocytogenes resulted either in prolonged survival compared with normal mice of the recipient haplotype or in definitive survival accompanied by a positive delayed-type sensitivity.

  18. Bone marrow mesenchymal stem cells suppressing activation of allogeneic cytokine-induced killer/natural killer cells either by direct or indirect interaction.

    PubMed

    Li, Yang; Qu, Yu H; Wu, Yan F; Liu, Ling; Lin, Xiang H; Huang, Ke; Wei, Jing

    2015-04-01

    Bone marrow mesenchymal stem cells (MSC) were recently found to be associated with some special immunological characteristics, the immunoregulatory effect of MSC was dose-dependent. Low amount of MSC was associated with mild immunosuppression or even immune activation, while the high amount of that was associated with significant immunosuppressive effect. In this study, by using a transwell system, we explored the effect of MSC on the cell cycle, apoptosis rate and the expression of CD69, an activation marker, on the allogeneic cord blood derived cytokine-induced killer(CIK)/natural killer(NK) cells. The results showed that either by transwell or mixed cell-cell co-culture, the MSC can effect CIK/NK cells on the cell cycle, such as arrested in the G0/G1 phase, diminished the ratio of cells in S, G2/M phase, and increased the apoptosis of them. MSC can also depress the expression of CD69 on these killer cells, as well as increased the ratio of CD4(+) CD25(+) CD127(low) T regulatory (Treg) cells in the CIK/NK cell culture system. We draw conclusions that either by transwell or mixed co-culture, the MSC can suppress activation of allogeneic CB-CIK/NK cells in a dose-dependent manner.

  19. A comparative study of the proliferation and osteogenic differentiation of human periodontal ligament cells cultured on β-TCP ceramics and demineralized bone matrix with or without osteogenic inducers in vitro.

    PubMed

    An, Shaofeng; Gao, Yan; Huang, Xiangya; Ling, Junqi; Liu, Zhaohui; Xiao, Yin

    2015-05-01

    The repair of bone defects that result from periodontal diseases remains a clinical challenge for periodontal therapy. β-tricalcium phosphate (β-TCP) ceramics are biodegradable inorganic bone substitutes with inorganic components that are similar to those of bone. Demineralized bone matrix (DBM) is an acid-extracted organic matrix derived from bone sources that consists of the collagen and matrix proteins of bone. A few studies have documented the effects of DBM on the proliferation and osteogenic differentiation of human periodontal ligament cells (hPDLCs). The aim of the present study was to investigate the effects of inorganic and organic elements of bone on the proliferation and osteogenic differentiation of hPDLCs using three-dimensional porous β-TCP ceramics and DBM with or without osteogenic inducers. Primary hPDLCs were isolated from human periodontal ligaments. The proliferation of the hPDLCs on the scaffolds in the growth culture medium was examined using a Cell-Counting kit-8 (CCK-8) and scanning electron microscopy (SEM). Alkaline phosphatase (ALP) activity and the osteogenic differentiation of the hPDLCs cultured on the β-TCP ceramics and DBM were examined in both the growth culture medium and osteogenic culture medium. Specific osteogenic differentiation markers were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). SEM images revealed that the cells on the β-TCP were spindle-shaped and much more spread out compared with the cells on the DBM surfaces. There were no significant differences observed in cell proliferation between the β-TCP ceramics and the DBM scaffolds. Compared with the cells that were cultured on β-TCP ceramics, the ALP activity, as well as the Runx2 and osteocalcin (OCN) mRNA levels in the hPDLCs cultured on DBM were significantly enhanced both in the growth culture medium and the osteogenic culture medium. The organic elements of bone may exhibit greater osteogenic differentiation effects

  20. Clinical and Histological Comparison of Extraction Socket Healing Following the Use of Autologous Platelet-Rich Fibrin Matrix (PRFM) to Ridge Preservation Procedures Employing Demineralized Freeze Dried Bone Allograft Material and Membrane

    PubMed Central

    Simon, B.I; Zatcoff, A.L; Kong, J.J.W; O’Connell, S.M

    2009-01-01

    Background: The healing potential of platelet growth factors has generated interest in using Platelet-Rich Plasma (PRP) in ridge preservation procedures. A canine study was performed to determine if extraction sites treated with platelet-rich fibrin matrix (PRFM) exhibit enhanced healing compared to sites treated with non-viable materials. Methods: Four dog’s extraction sockets were treated individually with PRFM, PRFM and membrane, Demineralized Freeze-Dried Bone Allograft (DFDBA) and membrane, PRFM and DFDBA, and untreated control. Treatment sequencing permitted clinical and histologic evaluation of healing at 10 days, 2, 3, 6 and 12 weeks. Results: Healing was more rapid in the PRFM and PRFM and membrane sites. By 3 weeks those sockets had osseous fill. Sites containing DFDBA had little new bone at 6 weeks. By 12 weeks those sockets had osseous fill but DFDBA particles were still noted in coronal areas. Conclusions: PRFM alone may be the best graft for ridge preservation procedures. Advantages: faster healing, and elimination of disadvantages involved in using barrier membranes. PMID:19543550

  1. Treated of type 1 diabetes mellitus in non-obese diabetic mice by transplantation of allogeneic bone marrow and pancreatic tissue

    SciTech Connect

    Yasumizu, R.; Sugiura, K.; Iwai, H.; Inaba, M.; Makino, S.; Ida, T.; Imura, H.; Hamashima, Y.; Good, R.A.; Ikehara, S.

    1987-09-01

    Non-obese diabetic (NOD) mice provide a model for type 1 diabetes mellitus. We previously showed that allogeneic bone marrow transplantation (ABMT) can prevent and treat insulitis and overt diabetes in NOD mice. However, ABMT alone could not be used to treat overt diabetes in NOD mice whose islets had been completely destroyed. To provide insulin-producing cells, pancreatic tissue from newborn mice was grafted under the renal capsules in combination with ABMT. The aims of concomitant ABMT are as follows. (i) It induces immunological tolerance to the donor-type major histocompatibility complex determinants and permits the host to accept subsequent pancreatic allografts from the bone marrow donor. (ii) ABMT replaces abnormal stem cells with normal stem cells. After transplantation of bone marrow plus newborn pancreas, NOD mice showed reduction of the glycosuria and a normal response in the glucose-tolerance test. Immunohistological study revealed the presence of clustered insulin-containing beta cells in the grafted pancreatic transplants. ABMT may become a viable treatment of established type 1 diabetes mellitus in humans.

  2. Recipient leukocyte infusion enhances the local and systemic graft-versus-neuroblastoma effect of allogeneic bone marrow transplantation in mice.

    PubMed

    Willems, Leen; Fevery, Sabien; Sprangers, Ben; Rutgeerts, Omer; Lenaerts, Caroline; Ibrahimi, Abdelilah; Gijsbers, Rik; Van Gool, Stefaan; Waer, Mark; Billiau, An D

    2013-11-01

    Allogeneic hematopoietic stem cell transplantation and donor leukocyte infusion (DLI) may hold potential as a novel form of immunotherapy for high-risk neuroblastoma. DLI, however, carries the risk of graft-versus-host disease (GvHD). Recipient leukocyte infusion (RLI) induces graft-versus-leukemia responses without GvHD in mice and is currently being explored clinically. Here, we demonstrate that both DLI and RLI, when given to mixed C57BL/6→A/J radiation chimeras carrying subcutaneous Neuro2A neuroblastoma implants, can slow the local growth of such tumors. DLI provoked full donor chimerism and GvHD; RLI produced graft rejection but left mice healthy. Flow cytometric studies showed that the chimerism of intratumoral leukocytes paralleled the systemic chimerism. This was associated with increased CD8/CD4 ratios, CD8+ T-cell IFN-γ expression and NK-cell Granzyme B expression within the tumor, following both DLI and RLI. The clinically safe anti-tumor effect of RLI was further enhanced by adoptively transferred naïve recipient-type NK cells. In models of intravenous Neuro2A tumor challenge, allogeneic chimeras showed superior overall survival over syngeneic chimeras. Bioluminescence imaging in allogeneic chimeras challenged with luciferase-transduced Neuro2A cells showed both DLI and RLI to prolong metastasis-free survival. This is the first experimental evidence that RLI can safely produce a local and systemic anti-tumor effect against a solid tumor. Our data indicate that RLI may provide combined T-cell and NK-cell reactivity effectively targeting Neuro2A neuroblastoma.

  3. Local delivery of allogeneic bone marrow and adipose tissue-derived mesenchymal stromal cells for cutaneous wound healing in a porcine model.

    PubMed

    Hanson, Summer E; Kleinbeck, Kyle R; Cantu, David; Kim, Jaeyhup; Bentz, Michael L; Faucher, Lee D; Kao, W John; Hematti, Peiman

    2016-02-01

    Wound healing remains a major challenge in modern medicine. Bone marrow- (BM) and adipose tissue- (AT) derived mesenchymal stromal/stem cells (MSCs) are of great interest for tissue reconstruction due to their unique immunological properties and regenerative potential. The purpose of this study was to characterize BM and AT-MSCs and evaluate their effect when administered in a porcine wound model. MSCs were derived from male Göttingen Minipigs and characterized according to established criteria. Allogeneic BM- or AT-MSCs were administered intradermally (1 x 10(6) cells) into partial-thickness wounds created on female animals, and covered with Vaseline® gauze or fibrin in a randomized pattern. Animals were euthanized at 7, 10, 14 and 21 days. Tissues were analyzed visually for healing and by microscopic examination for epidermal development and remodelling. Polymerase chain reaction (PCR) was used to detect the presence of male DNA in the specimens. All wounds were healed by 14 days. MSC-injected wounds were associated with improved appearance and faster re-epithelialization compared to saline controls. Evaluation of rete ridge depth and architecture showed that MSC treatment promoted a faster rate of epidermal maturation. Male DNA was detected in all samples at days 7 and 10, suggesting the presence of MSCs. We showed the safety, feasibility and potential efficacy of local injection of allogeneic BM- and AT-MSCs for treatment of wounds in a preclinical model. Our data in this large animal model support the potential use of BM- and AT-MSC for treatment of cutaneous wounds through modulation of healing and epithelialization.

  4. Dipeptidyl peptidase IV (DPPIV/CD26) inhibition does not improve engraftment of unfractionated syngeneic or allogeneic bone marrow after nonmyeloablative conditioning.

    PubMed

    Schwaiger, Elisabeth; Klaus, Christoph; Matheeussen, Veerle; Baranyi, Ulrike; Pilat, Nina; Ramsey, Haley; Korom, Stephan; De Meester, Ingrid; Wekerle, Thomas

    2012-02-01

    In order to develop minimally toxic bone marrow transplantation (BMT) protocols suitable for use in a wider range of indications, it is important to identify ways to enhance BM engraftment at a given level of recipient conditioning. CXCL12/stromal cell-derived factor-1α plays a crucial physiological role in homing of hematopoietic stem cells to BM. It is regulated by the ectopeptidase dipeptidyl peptidase IV (DPPIV; DPP4) known as CD26, which cleaves dipeptides from the N-terminus of polypeptide chains. Blocking DPPIV enzymatic activity had a beneficial effect on hematopoietic stem cell engraftment in various but very specific experimental settings. Here we investigated whether inhibition of DPPIV enzymatic activity through Diprotin A or sitagliptin (Januvia) improves BM engraftment in nonmyeloablative murine models of syngeneic (i.e., CD45-congenic) and allogeneic (i.e., Balb/c to B6) BMT (1 Gy total body irradiation, 10-15 × 10(6) unseparated BM cells/mouse). Neither Diprotin A administered in vivo at the time of BMT and/or used for in vitro pretreatment of BM nor sitagliptin administered in vivo had a detectable effect on the level of multilineage chimerism (follow-up >20 weeks). Similarly, sitagliptin did not enhance chimerism after allogeneic BMT, even though DPPIV enzymatic activity measured in serum was profoundly inhibited (>98% inhibition at peak exposure). Our results provide evidence that DPPIV inhibition via Diprotin A or sitagliptin does not improve engraftment of unseparated BM in a nonmyeloablative BMT setting.

  5. Experimental bladder regeneration using a poly-l-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells

    PubMed Central

    Yudintceva, Natalia M; Nashchekina, Yulia A; Blinova, Miralda I; Orlova, Nadezhda V; Muraviov, Alexandr N; Vinogradova, Tatiana I; Sheykhov, Magomed G; Shapkova, Elena Y; Emeljannikov, Dmitriy V; Yablonskii, Petr K; Samusenko, Igor A; Mikhrina, Anastasiya L; Pakhomov, Artem V; Shevtsov, Maxim A

    2016-01-01

    In the present study, a poly-l-lactide/silk fibroin (PL-SF) bilayer scaffold seeded with allogenic bone marrow stromal cells (BMSCs) was investigated as a potential approach for bladder tissue engineering in a model of partial bladder wall cystectomy in rabbits. The inner porous layer of the scaffold produced from silk fibroin was designed to promote cell proliferation and the outer layer produced from poly-l-lactic acid to serve as a waterproof barrier. To compare the feasibility and efficacy of BMSC application in the reconstruction of bladder defects, 12 adult male rabbits were divided into experimental and control groups (six animals each) that received a scaffold seeded with BMSCs or an acellular one, respectively. For BMSC tracking in the graft in in vivo studies using magnetic resonance imaging, cells were labeled with superparamagnetic iron oxide nanoparticles. In vitro studies demonstrated high intracellular incorporation of nanoparticles and the absence of a toxic influence on BMSC viability and proliferation. Following implantation of the graft with BMSCs into the bladder, we observed integration of the scaffold with surrounding bladder tissues (as detected by magnetic resonance imaging). During the follow-up period of 12 weeks, labeled BMSCs resided in the implanted scaffold. The functional activity of the reconstructed bladder was confirmed by electromyography. Subsequent histological assay demonstrated enhanced biointegrative properties of the PL-SF scaffold with cells in comparison to the control graft, as related to complete regeneration of the smooth muscle and urothelium tissues in the implant. Confocal microscopy studies confirmed the presence of the superparamagnetic iron oxide nanoparticle-labeled BMSCs in newly formed bladder layers, thus indicating the role of stem cells in bladder regeneration. The results of this study demonstrate that application of a PL-SF scaffold seeded with allogenic BMSCs can enhance biointegration of the graft in

  6. Experimental bladder regeneration using a poly-l-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells

    PubMed Central

    Yudintceva, Natalia M; Nashchekina, Yulia A; Blinova, Miralda I; Orlova, Nadezhda V; Muraviov, Alexandr N; Vinogradova, Tatiana I; Sheykhov, Magomed G; Shapkova, Elena Y; Emeljannikov, Dmitriy V; Yablonskii, Petr K; Samusenko, Igor A; Mikhrina, Anastasiya L; Pakhomov, Artem V; Shevtsov, Maxim A

    2016-01-01

    In the present study, a poly-l-lactide/silk fibroin (PL-SF) bilayer scaffold seeded with allogenic bone marrow stromal cells (BMSCs) was investigated as a potential approach for bladder tissue engineering in a model of partial bladder wall cystectomy in rabbits. The inner porous layer of the scaffold produced from silk fibroin was designed to promote cell proliferation and the outer layer produced from poly-l-lactic acid to serve as a waterproof barrier. To compare the feasibility and efficacy of BMSC application in the reconstruction of bladder defects, 12 adult male rabbits were divided into experimental and control groups (six animals each) that received a scaffold seeded with BMSCs or an acellular one, respectively. For BMSC tracking in the graft in in vivo studies using magnetic resonance imaging, cells were labeled with superparamagnetic iron oxide nanoparticles. In vitro studies demonstrated high intracellular incorporation of nanoparticles and the absence of a toxic influence on BMSC viability and proliferation. Following implantation of the graft with BMSCs into the bladder, we observed integration of the scaffold with surrounding bladder tissues (as detected by magnetic resonance imaging). During the follow-up period of 12 weeks, labeled BMSCs resided in the implanted scaffold. The functional activity of the reconstructed bladder was confirmed by electromyography. Subsequent histological assay demonstrated enhanced biointegrative properties of the PL-SF scaffold with cells in comparison to the control graft, as related to complete regeneration of the smooth muscle and urothelium tissues in the implant. Confocal microscopy studies confirmed the presence of the superparamagnetic iron oxide nanoparticle-labeled BMSCs in newly formed bladder layers, thus indicating the role of stem cells in bladder regeneration. The results of this study demonstrate that application of a PL-SF scaffold seeded with allogenic BMSCs can enhance biointegration of the graft in

  7. Persistence of T8+/HNK-1+ suppressor lymphocytes in the blood of long-term surviving patients after allogeneic bone marrow transplantation.

    PubMed

    Leroy, E; Calvo, C F; Divine, M; Gourdin, M F; Baujean, F; Ben Aribia, M H; Mishal, Z; Vernant, J P; Farcet, J P; Senik, A

    1986-10-01

    Fifteen patients and their respective bone marrow donors were entered in this study 1 to 5 yr after allogeneic bone marrow transplantation. Peripheral blood E rosetting (T) cells were analyzed for their phenotypic characteristics as well as for their ability to regulate Ig synthesis in the in vitro PWM system. A close relationship was found between a high proportion of T8+/HNK-1+ cells and/or T8+/HLA-DR+ cells and a strong (greater than or equal to 50%) inhibition of the antibody response. It was noteworthy that even the patients without suppressor activity had high proportions of such cells when compared with normal marrow donors. Moreover, the suppression occurred irrespective of the presence or absence of chronic GVHD. Through negative selection experiments (with MAb and complement) and through immunofluorescence cell sorting, it was shown that the suppressor cells expressed the T8+, HNK-1+, HLA-DR- phenotype. They did not carry the Leu-11, NKH1A, or NKH2 determinants, which are expressed on mature functional NK cells. When examined by electron microscopy, they exhibited a morphology of resting agranular lymphocytes. The significant increase of these suppressor cells among the BMT patients was not correlated with clinical syndromes such as chronic GVHD or opportunistic viral infections, which argues against the notion of in vivo profound immunodeficiency coexisting with these cells. PMID:2944951

  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. Adult thymus transplantation with allogeneic intra-bone marrow–bone marrow transplantation from same donor induces high thymopoiesis, mild graft-versus-host reaction and strong graft-versus-tumour effects

    PubMed Central

    Miyake, Takashi; Hosaka, Naoki; Cui, Wenhao; Nishida, Teruhisa; Takaki, Takashi; Inaba, Muneo; Kamiyama, Yasuo; Ikehara, Susumu

    2009-01-01

    Although allogeneic bone marrow transplantation (BMT) plus donor lymphocyte infusion (DLI) is performed for solid tumours to enhance graft-versus-tumour (GVT) effects, a graft-versus-host reaction (GVHR) is also elicited. We carried out intra-bone marrow–bone marrow transplantation (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor to supply alloreactive T cells continually. Normal mice treated with IBM-BMT + ATT survived for a long time with high donor-derived thymopoiesis and mild GVHR. The percentage of CD4+ FoxP3+ regulatory T cells in the spleen of the mice treated with IBM-BMT + ATT was lower than in normal B6 mice or mice treated with IBM-BMT alone, but higher than in mice treated with IBM-BMT + DLI; the mice treated with IBM-BMT + DLI showed severe GVHR. In tumour-bearing mice, tumour growth was more strongly inhibited by IBM-BMT + ATT than by IBM-BMT alone. Mice treated with IBM-BMT + a high dose of DLI also showed tumour regression comparable to that of mice treated with IBM-BMT + ATT but died early of GVHD. By contrast, mice treated with IBM-BMT + a low dose of DLI showed longer survival but less tumour regression than the mice treated with IBM-BMT + ATT. Histologically, significant numbers of CD8+ T cells were found to have infiltrated the tumour in the mice treated with IBM-BMT + ATT. The number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL)-positive apoptotic tumour cells also significantly increased in the mice treated with IBM-BMT + ATT. Allogeneic IBM-BMT + ATT thus can induce high thymopoiesis, preserving strong GVT effects without severe GVHR. PMID:18778285

  10. 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.

  11. The evolution of treatment strategies for patients with chronic myeloid leukemia relapsing after allogeneic bone marrow transplantation: Can tyrosine kinase inhibitors replace donor lymphocyte infusions?

    PubMed Central

    Zeidner, Joshua F.; Zahurak, Marianna; Rosner, Gary L.; Gocke, Christopher D.; Jones, Richard J.; Smith, Douglas

    2014-01-01

    The optimal treatment for chronic myeloid leukemia (CML) relapsing following allogeneic bone marrow transplantation (alloBMT) is unknown. We performed a single-center retrospective analysis of 71 consecutive patients undergoing alloBMT for CML from 1995–2008. A multi-state model was used to quantify the cumulative incidences of complete molecular response (CMR) and death following alloBMT. The primary analysis was the comparison of three treatment interventions (tyrosine kinase inhibitor: TKI, donor lymphocyte infusion: DLI, and TKI+DLI) for relapsed disease post-alloBMT. Forty-five (63%) patients relapsed post-alloBMT (molecular relapse: n=16, cytogenetic relapse: n=20, hematologic relapse: n=2, advanced phase relapse: n=7) and 40 patients underwent one of three treatments: TKI-only (n=13), DLI-only (n=11), or TKI+DLI (n=16). Although not statistically significant, the TKI-only group had the highest cumulative incidence of CMR and the lowest cumulative incidence of death compared to DLI and TKI+DLI. These data support the finding that TKI therapy is active in the post-alloBMT setting. PMID:24712979

  12. Predominant expression of circulating CD3+ lymphocytes bearing gamma T cell receptor in a prolonged immunodeficiency after allogeneic bone marrow transplantation.

    PubMed

    Vilmer, E; Guglielmi, P; David, V; Leca, G; Rabian, C; Degos, L; Boiron, M; Bensussan, A

    1988-09-01

    The cell surface expression of alpha:beta heterodimer was studied using WT31 monoclonal antibody, in peripheral blood lymphocytes (PBL) from a patient who developed a prolonged immunodeficiency after allogeneic bone marrow transplantation. This patient, grafted for chronic myelogenous leukemia, received T cell depleted bone marrow from her HLA, A, B, D matched sibling. The late occurrence of opportunistic infection, led us to analyze the phenotype of patient PBL. 70% of PBL were CD3+ and 29% WT31+, indicating that the majority of CD3+ PBL did not express the alpha:beta heterodimer. Transcription of the genes encoding the alpha, beta, and gamma chains was assessed in cell lines derived from PBL, by Northern blot analysis. We showed that the CD3+ WT31- subset expressed a truncated, beta mRNA (1.0 kb) and also truncated alpha transcript (1.4 kb). To determine the CD3-associated structure on CD3+ WT31- cell line, immunoprecipitation assays were performed using monoclonal anti-CD3 and an hetero antiserum against gamma peptides. These CD3+ WT31- cells expressed a disulfide linked dimer, composed of products of gamma gene (37 kD, 40 kD) and of undefined delta chain (45 kD). Functional analyses were performed in PBL before and after sorting with WT31 and anti-CD3 antibody. These circulating CD3+ WT31- cells were unable to proliferate when triggered with anti-T3 beads and they seemed to mediate a suppressor activity on CD3+ WT31+ cells.

  13. Predominant expression of circulating CD3+ lymphocytes bearing gamma T cell receptor in a prolonged immunodeficiency after allogeneic bone marrow transplantation.

    PubMed Central

    Vilmer, E; Guglielmi, P; David, V; Leca, G; Rabian, C; Degos, L; Boiron, M; Bensussan, A

    1988-01-01

    The cell surface expression of alpha:beta heterodimer was studied using WT31 monoclonal antibody, in peripheral blood lymphocytes (PBL) from a patient who developed a prolonged immunodeficiency after allogeneic bone marrow transplantation. This patient, grafted for chronic myelogenous leukemia, received T cell depleted bone marrow from her HLA, A, B, D matched sibling. The late occurrence of opportunistic infection, led us to analyze the phenotype of patient PBL. 70% of PBL were CD3+ and 29% WT31+, indicating that the majority of CD3+ PBL did not express the alpha:beta heterodimer. Transcription of the genes encoding the alpha, beta, and gamma chains was assessed in cell lines derived from PBL, by Northern blot analysis. We showed that the CD3+ WT31- subset expressed a truncated, beta mRNA (1.0 kb) and also truncated alpha transcript (1.4 kb). To determine the CD3-associated structure on CD3+ WT31- cell line, immunoprecipitation assays were performed using monoclonal anti-CD3 and an hetero antiserum against gamma peptides. These CD3+ WT31- cells expressed a disulfide linked dimer, composed of products of gamma gene (37 kD, 40 kD) and of undefined delta chain (45 kD). Functional analyses were performed in PBL before and after sorting with WT31 and anti-CD3 antibody. These circulating CD3+ WT31- cells were unable to proliferate when triggered with anti-T3 beads and they seemed to mediate a suppressor activity on CD3+ WT31+ cells. Images PMID:3047169

  14. Effect of Er:YAG laser holes on osteoinduction in demineralized rat calvarial allografts.

    PubMed

    O'Donnell, R J; Deutsch, T F; Flotte, R J; Lorente, C A; Tomford, W W; Mankin, H J; Schomacker, K T

    1996-01-01

    Massive cortical autografts and allografts have been found to incorporate into host bone very slowly and thus are subject to complications such as fatigue fracture and infection. In order to understand and improve the process of osteogenesis in these types of bone grafts, a new experimental model was developed using bone discs from rat calvaria prepared by demineralization and drilling of 0.5 mm diameter holes with a pulsed, 2.94 microns wavelength Erbium:Yttrium-Aluminum-Garnet laser. Four types of bone discs were analyzed: untreated (Type I), demineralized (Type II), laser-ablated (Type III), and laser-ablated then demineralized (Type IV). The discs were transplanted into a subcutaneous site in adult Sprague-Dawley rats and followed for as long as 6 weeks. Histologic analysis of the discs at weekly intervals with use of hematoxylin and eosin staining confirmed the presence of new bone growth in Type-II and Type-IV discs. The amount of new bone growth in each disc was estimated by determining the mineral x-ray attenuation coefficient, which is proportional to mineral density, from digitized radiographs of the discs. The results showed that the processes of demineralization (P < 0.001) and laser ablation with demineralization (p < 0.05) were both significant in enhancing new bone growth in this model. This study demonstrated that osteoinduction can be fostered in cortical bone through the processes of demineralization and laser ablation. To the extent that laser ablation may allow maintenance of structural integrity while altering the surface geometry in such a way as to promote ingrowth of new bone, this experimental model represents an advance in understanding how osteogenesis in cortical bone grafts might be improved. PMID:8618152

  15. BENIGN BONE TUMORS AND TUMOR-LIKE BONE LESIONS: TREATMENT UPDATE AND NEW TRENDS

    PubMed Central

    Nogueira Drumond, José Marcos

    2015-01-01

    The treatment of benign bone tumors (BBT) and tumor-like bone lesions (TBL) has observed the introduction of new drugs, such as intravenous bisphosphonates, which have ossified bone lesions caused by fibrous dysplasia. Aneurismal bone cyst has been treated with sclerosing agents by percutaneous injection, yielding good results. Adjuvants allow joint salvage, maintenance of movements and function, with low rates of recurrence. Among them, the most used ones are bone cement (PMMA), phenol, nitrogen-based cryotherapy, hydrogen peroxide, ethanol and radiotherapy. New methods of treatment include thermal ablation with radiofrequency and laser, mainly utilized for treating osteoid osteoma. Arthroscopy allows resection of benign intra-joint lesions and assists the surgery of subchondral tumors. A great advance is the utilization of synthetic bone substitutes, which are a mixture of osteoinductive growth factors and osteoconductive ceramics, and have presented comparable results to autogenous bone grafts. There is a recent trend for closed treatments, with percutaneous injection of demineralized bone matrix (DBM) and calcium sulfate. Autogenous cancellous bone graft remains as the gold standard. Vascularized fibula graft, on the other hand, incorporates faster in the treatment of large destructive lesions. Also, allogenic cortical support allows structural augmentation for aggressive tumors. Freeze-dried allografts are used to fill contained defects and as expanders of autografts. Joint endoprosthesis may be used in large destructive lesions of the distal femur, hip and shoulder. PMID:27004184

  16. Pathology of the thymus after allogeneic bone marrow transplantation in man. A histologic immunohistochemical study of 36 patients.

    PubMed Central

    Müller-Hermelink, H. K.; Sale, G. E.; Borisch, B.; Storb, R.

    1987-01-01

    A major hypothesis to explain the immunodeficiency associated with bone marrow transplantation states that thymic epithelial damage due to graft-versus-host disease (GVHD) abrogates or delays the recovery of normal immunologic function. This study evaluated the thymus glands of 36 human bone marrow transplant recipients dying between 4 and 1742 days after transplant using histology, histochemistry, and immunohistology. The observations lead to a model of thymic damage by irradiation, chemotherapy, and GVHD in which early injury by all three of these agents results in profound thymic atrophy followed by long-delayed restitution. Patients undergoing total body irradiation showed more severe damage to thymic cortical and medullary epithelium than did patients undergoing chemotherapy alone as preparation for transplantation. Patients with GVHD showed additional damage in the form of individual thymic epithelial cell death and showed HLA-DR surface protein expression on thymic epithelium during GVHD. Longer-term survivors showed a profoundly delayed restitution of normal thymic epithelium and delayed evidence of restored lymphopoiesis. A few patients dying late after transplant showed evidence of reconstitution of normal thymic structure or nodules of lymphopoiesis in focal areas of epithelial-cell reconstitution. Evidence of such lymphopoiesis was seen at times ranging between 90 and 1742 days after grafting. The data are consistent with a model of long-standing thymic damage caused by GVHD which is reversible after the development of tolerance. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:3314529

  17. Analyses of Donor-Derived Keratinocytes in Hairy and Nonhairy Skin Biopsies of Female Patients Following Allogeneic Male Bone Marrow Transplantation

    PubMed Central

    Nemeth, Krisztian; Key, Sharon; Bottlik, Gyula; Masszi, Tamas; Karpati, Sarolta

    2012-01-01

    Skin samples taken from 6 female patients receiving allogeneic bone marrow transplants (BMT) from male siblings (n=5) or from unrelated human leukocyte antigen (HLA)-matched male donor (n=1) due to hematological malignancies were studied for the presence of donor cells. One nontransplanted male and 1 female control that received female BM were used as further controls of the technique. Skin biopsies were taken from the scalp and the back from each patient 12–16 years after the successful BMT. We have found donor chimerism in all of the 6 patients in both of their biopsies. Using single and double immunostainings in combination with Y chromosome hybridization, we observed that there are cytokeratin-expressing donor-derived cells in the epidermis of all the 6 patients, the numbers being slightly higher in the scalp (0.37%–1.78%) than in the back (0.32%–1.08%) biopsies. The indication for BMT, and the age of the patient did not seem to have any effect on the numbers found. A few of the double-labeled cells also stained for Ki67, a marker of cellular proliferation, suggesting that the engrafted cells were able to further divide in the epidermis. In 2 patients we observed patches of donor keratinocytes within the epidermis, suggesting a clonal origin. We conclude that in agreement with some and in contrast to other published studies, BM-derived circulating cells are able to engraft in the human skin and to further proliferate there and thus contribute to tissue renewal. These data raise the possibility to use BM cells in regenerative medicine to help in extended injuries, large surface burns, or lack of skin due to other reasons. PMID:21288071

  18. IFN-γ Receptor Deficient Donor T cells Mediate Protection from Graft-versus-Host Disease and Preserve Graft-versus-Tumor Responses After Allogeneic Bone Marrow Transplantation

    PubMed Central

    Sun, Kai; Hsiao, Hui-Hua; Li, Minghui; Ames, Erik; Bouchlaka, Myriam; Welniak, Lisbeth A.; Hagino, Takeshi; Jagdeo, Jared; Pai, Chien-Chun; Chen, Mingyi; Blazar, Bruce R.; Abedi, Mehrdad; Murphy, William J.

    2012-01-01

    Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (BMT). It has been previously reported that lung GVHD severity directly correlates with the expansion of donor Th17 cells in the absence of IFN-γ. However, the consequence of Th17-associated lung GVHD in the presence of IFN-γ has not been well-characterized. In the current study, T cells from IFN-γ receptor knockout (IFN-γR-/-) mice, capable of producing IFN-γ but unable to signal in response to IFN-γ, have been used to further elucidate the role of IFN-γ in GVHD. We found the transfer of donor T cells from either IFN-γR-/- or IFN-γ knockout (IFN-γ-/-) mice resulted in significant increases in donor Th17 cells in the lung. Marked increases in IL4-producing Th2 cells infiltrating the lungs were also observed in the mice of donor IFN-γR-/- T cells. Interestingly, despite the presence of these cells, these mice did not show the severe immune mediated histopathological lung injury observed in mice receiving donor IFN-γ-/- T cells. Increases in lung GVHD did occur in mice with donor IFN-γR-/- T cells when treated in vivo with anti-IFN-γ demonstrating that the cytokine has a protective role on host tissues in GVHD. A survival benefit from acute GVHD was also observed using donor cells from IFN-γR-/-T cells compared with control donors. Importantly, tumor-bearing mice receiving IFN-γR-/- T cells, versus wild-type donor T cells, displayed similar graft-versus tumor (GVT) effects. These results demonstrate the critical role of the IFN-γ on host tissues and cell effector functions in GVHD/GVT. PMID:22778394

  19. Successful non-myeloablative allogenic bone marrow transplantation in a child with severe congenital neutropenia complicated by chronic pulmonary infection.

    PubMed

    Nino, Nanako; Kozaki, Aiko; Hasegawa, Daiichiro; Ueda, Go; Takahashi, Hironobu; Miyata, Kenji; Ochi, Satoshi; Yamashita, Tatsuya; Takafuji, Satoru; Uemura, Suguru; Yokoi, Takehito; Saito, Atsuro; Ishida, Toshiaki; Kawasaki, Keiichiro; Nakamura, Kazuhiro; Kobayashi, Masao; Kosaka, Yoshiyuki

    2016-06-01

    We herein describe a 2-year-old boy with severe congenital neutropenia (SCN) who was successfully treated with reduced-intensity bone marrow transplantation (HSCT). He had suffered recurrent episodes of bacterial pneumonia from 12 months of age, and was found to have severe neutropenia with white blood cell counts below 100/μl. The patient harbored a heterozygous missense mutation in ELANE exon 4 (p.Gln134Pro, NM_001972.2: c.401A>C). This was a novel mutation. Due to intractable pneumonia and severe persistent neutropenia, reduced-intensity HSCT was performed from an HLA-matched sibling donor. The preparative regimen consisted of melphalan, fludarabine, and 4 Gy of total body irradiation. Hematopoietic engraftment was rapidly obtained, i.e., by day +14, and complete donor chimerism was subsequently achieved. The lung complications observed pre-transplantation markedly improved after neutrophil recovery, i.e., by day +60. We concluded that HSCT is a useful treatment for SCN patients, especially for those at high risk of leukemic transformation. Fludarabine-based reduced-intensity HSCT may represent a safe and effective therapeutic option for patients with SCN who need HSCT even if they have intractable infectious complications. PMID:27384854

  20. A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia

    PubMed Central

    2013-01-01

    Background Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI. Methods Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment – related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb. Results Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells. Conclusion BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies. Trial registration NIH website (http

  1. Differential effects of the absence of interferon-gamma and IL-4 in acute graft-versus-host disease after allogeneic bone marrow transplantation in mice.

    PubMed Central

    Murphy, W J; Welniak, L A; Taub, D D; Wiltrout, R H; Taylor, P A; Vallera, D A; Kopf, M; Young, H; Longo, D L; Blazar, B R

    1998-01-01

    Graft-versus-host disease (GVHD), in which immunocompetent donor cells attack the host, remains a major cause of morbidity after allogeneic bone marrow transplantation (BMT). To understand the role of cytokines in the pathobiology of GVHD, we used cytokine knockout (KO) mice as a source of donor T cells. Two different MHC-disparate strain combinations were examined: BALB/c (H2(d)) donors into lethally irradiated C57BL/6 (H2(b)) recipients or C57BL/6 (H2(b)) donors into B10.BR (H2(k)) recipients. Donor cells were from mice in which either the interferon-gamma (IFN-gamma) or the IL-4 gene was selectively disrupted to understand the role of these cytokines in acute GVHD. In both strain combinations the same pattern was noted with regard to GVHD onset and morbidity. All mice exhibited the classic signs of acute GVHD: weight loss with skin, gut, and liver pathology resulting in morbidity and mortality. Surprisingly, donor cells obtained from mice lacking IFN-gamma gave rise to accelerated morbidity from GVHD when compared with cells from wild-type control donors. Similar results were obtained using normal donors when neutralizing antibodies to IFN-gamma were administered immediately after the BMT. These results suggest that IFN-gamma plays a role in protection from acute GVHD. In marked contrast, cells obtained from IL-4 KO mice resulted in protection from GVHD compared with control donors. Splenocytes from IFN KO mice stimulated with a mitogen proliferated to a significantly greater extent and produced more IL-2 compared with splenocytes obtained from IL-4 KO or control mice. Additionally, there was increased IL-2 production in the spleens of mice undergoing GVHD using IFN-gamma KO donors. These results therefore indicate, with regard to the TH1/ TH2 cytokine paradigm, the absence of a TH1-type cytokine can be deleterious in acute GVHD, whereas absence of a TH2 cytokine can be protective. PMID:9802888

  2. Effect of Ex Vivo Culture of CD34+ Bone Marrow Cells on Immune Reconstitution of XSCID Dogs Following Allogeneic Bone Marrow Transplantation

    PubMed Central

    Kennedy, Douglas R.; McLellan, Kyle; Moore, Peter F.; Henthorn, Paula S.; Felsburg, Peter J.

    2009-01-01

    Successful genetic treatment of most primary immunodeficiencies or hematological disorders will require the transduction of pluripotent, self-renewing hematopoietic stem cells (HSC) rather than their progeny in order to achieve enduring production of genetically corrected cells and durable immune reconstitution. Current ex vivo transduction protocols require manipulation of HSC by culture in cytokines for various lengths of time depending upon the retroviral vector that may force HSC to enter pathways of proliferation, and possibly differentiation, that could limit their engraftment potential, pluripotentiality and long-term repopulating capacity. We have compared the ability of normal CD34+ cells cultured in a standard cytokine cocktail for 18 hours or 4.5 days to reconstitute XSCID dogs following bone marrow transplantation in the absence of any pre-transplant conditioning with that of freshly isolated CD34+ cells. CD34+ cells cultured under standard γ-retroviral transduction conditions (4.5 days) showed decreased engraftment potential and ability to sustain long-term thymopoiesis. In contrast, XSCID dogs transplanted with CD34+ cells cultured for 18 hours showed a robust T cell immune reconstitution similar to dogs transplanted with freshly isolated CD34+ cells, however, the ability to sustain long-term thymopoiesis was impaired. These results emphasize the need to determine ex vivo culture conditions that maintain both the engraftment potential and “stem cell” potential of the cultured cells. PMID:19450750

  3. Comparison of applying particulate demineralized bone matrix (DBM), putty DBM and open flap debridement in periodontal horizontal bone defects. A 12-month longitudinal, multi-centre, triple-blind, split-mouth, randomized, controlled clinical study. Part 2 - evaluation of the interdental soft tissue.

    PubMed

    Kaya, Y; Yalim, M; Bahçecitapar, M; Baloş, K

    2009-07-01

    To date, there have been many studies clinically evaluating periodontal regenerative procedures by the help of routinely used hard and soft tissue parameters; however, these parameters are not capable of assessing interdental soft tissue located above the regenerative periodontal surgery area. The purpose of this study was to assess interproximal soft tissue changes following application of (i) particulate form demineralized bone matrix (DBM), (ii) putty form DBM and (ii) open flap debridement (OFD, control), using modified curtain technique in the treatment of interproximal suprabony (horizontal) defects located in anterior maxillary region, as previously reported. Twenty-five chronic periodontitis patients with 125 interproximal surgery sites (radiologically >or=4 mm horizontal bone defect) were also participate in this second stage of the triple-blind, split mouth, randomized, controlled clinical trial. Surgery sites were assessed by (i) plaque index (PI), (ii) gingival index (GI), (iii) the presence of interdental soft tissue clefts or craters and (iv) the loss of interdental papilla height by using papilla presence index (PPI), during the healing period. At the baseline and 3, 6, 9 and 12 months after the operations, these measurements were repeated. In all groups, there is a significant increase in the prevalence of soft tissue cleft and crater formation (P < 0.01), with increase in PI and GI scores at interdental soft tissue defect areas (P < 0.001), 3 months after the operations. There was also an increase in PPI scores after the operations in all treatment groups (P < 0.01). Three procedures affected the interproximal soft tissues similarly. There was no significant difference among groups in terms of all parameters (P > 0.05). Particulate DBM, putty DBM and OFD demostrated similar interproximal soft tissue changes especially increasing interproximal PI and GI scores in 3 months follow-up. PMID:19453849

  4. Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the infectious diseases working party (AGIHO) of the german society of haematology and oncology.

    PubMed

    Krüger, W H; Bohlius, J; Cornely, O A; Einsele, H; Hebart, H; Massenkeil, G; Schüttrumpf, S; Silling, G; Ullmann, A J; Waldschmidt, D T; Wolf, H-H

    2005-08-01

    Patients undergoing allogeneic stem cell transplantation are at high risk for infection with a variety of pathogens during different phases of the procedure. Bacteria and fungi predominate the first phase until engraftment. During the second phase, from engraftment to about day 100, major infectious problems are caused by fungi and cytomegalovirus. Both pathogens remain important under continued immunosuppression, however, in the late post-transplantation period infections with encapsulated bacteria may become a problem. In this review the Infectious Diseases Working Party of the DGHO gives recommendations for prophylaxis of infections under allogeneic stem cell transplantation with drugs and other measures. The aim of the group was to do this on an evidence-based-medicine rating, if possible.

  5. Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Société Française de Greffe de moelle (SFGM).

    PubMed

    Michallet, M; Tanguy, M L; Socié, G; Thiébaut, A; Belhabri, A; Milpied, N; Reiffers, J; Kuentz, M; Cahn, J Y; Blaise, D; Demeocq, F; Jouet, J P; Michallet, A S; Ifrah, N; Vilmer, E; Molina, L; Michel, G; Lioure, B; Cavazzana-Calvo, M; Pico, J L; Sadoun, A; Guyotat, D; Attal, M; Curé, H; Bordigoni, P; Sutton, L; Buzyn-Veil, A; Tilly, M; Keoirruer, N; Feguex, N

    2000-02-01

    Although recurrent malignancy is the most frequent indication for second stem cell transplantation (2nd SCT), there are few reports that include sufficiently large numbers of patients to enable prognostic factor analysis. This retrospective study includes 150 patients who underwent a 2nd SCT for relapsed acute myeloblastic leukaemia (n = 61), acute lymphoblastic leukaemia (n = 47) or chronic myeloid leukaemia (n = 42) after a first allogeneic transplant (including 26 T-cell-depleted). The median interval between the first transplant and relapse, and between relapse and second transplant was 17 months and 5 months respectively. After the 2nd SCT, engraftment occurred in 93% of cases, 32% of patients developed acute graft-vs.-host disease (GVHD) >/= grade II and 38% chronic GVHD. The 5-year overall and disease-free survival were 32 +/- 8% and 30 +/- 8%, respectively, with a risk of relapse of 44 +/- 12% and a transplant-related mortality of 45 +/- 9%. In a multivariate analysis, five factors were associated with a better outcome after 2nd SCT: age < 16 years at second transplant; relapse occurring more than 12 months after the first transplant; transplantation from a female donor; absence of acute GVHD; and the occurrence of chronic GVHD. The best candidates for a second transplant are likely to be patients with acute leukaemia in remission before transplant, in whom the HLA-identical donor was female and who relapsed more than 1 year after the first transplant.

  6. The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation.

    PubMed

    Hill, G R; Ferrara, J L

    2000-05-01

    Acute graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT), limits the application of this curative but toxic therapy. Studies of inflammatory pathways involved in GVHD in animals have shown that the gastrointestinal (GI) tract plays a major role in the amplification of systemic disease. Damage to the GI tract increases the translocation of inflammatory stimuli such as endotoxin, which promotes further inflammation and additional GI tract damage. The GI tract is therefore critical to the propagation of the "cytokine storm" characteristic of acute GVHD. Experimental approaches to the prevention of GVHD include reducing the damage to the GI tract by fortification of the GI mucosal barrier through novel "cytokine shields" such as IL-11 or keratinocyte growth factor. Such strategies have reduced GVHD while preserving a graft-versus-leukemia effect in animal models, and they now deserve formal testing in carefully designed clinical trials. (Blood. 2000;95:2754-2759)

  7. Principles of demineralization: modern strategies for the isolation of organic frameworks. Part I. Common definitions and history.

    PubMed

    Ehrlich, Hermann; Koutsoukos, Petros G; Demadis, Konstantinos D; Pokrovsky, Oleg S

    2008-12-01

    In contrast to biomineralization phenomena, that are among the most widely studied topics in modern material and earth science and biomedicine, much less is systematized on modern view of demineralization. Biomineralized structures and tissues are composites, containing a biologically produced organic matrix and nano- or microscale amorphous or crystalline minerals. Demineralization is the process of removing the inorganic part, or the biominerals, that takes place in nature via either physiological or pathological pathways in organisms. In vitro demineralization processes, used to obtain mechanistic information, consist in the isolation of the mineral phase of the composite biomaterials from the organic matrix. Physiological and pathological demineralization include, for example, bone resorption mediated by osteoclasts. Bioerosion, a more general term for the process of deterioration of the composite biomaterials represents chemical deterioration of the organic and mineral phase followed by biological attack of the composite by microorganisms and enzymes. Bioerosional organisms are represented by endolithic cyanobacteria, fungi, algae, plants, sponges, phoronids and polychaetes, mollusks, fish and echinoids. In the history of demineralization studies, the driving force was based on problems of human health, mostly dental caries. In this paper we summarize and integrate a number of events, discoveries, milestone papers and books on different aspect of demineralization during the last 400 years. Overall, demineralization is a rapidly growing and challenging aspect of various scientific disciplines such as astrobiology, paleoclimatology, geomedicine, archaeology, geobiology, dentistry, histology, biotechnology, and others to mention just a few. PMID:18403210

  8. An alternative treatment option for a bony defect from large odontoma using recycled demineralization at chairside.

    PubMed

    Lee, JuHyon; Lee, Eun-Young; Park, Eun-Jin; Kim, Eun-Suk

    2015-04-01

    Odontoma is the most common odontogenic benign tumor, and the treatment of choice is generally surgical removal. After excision, bone grafts may be necessary depending on the need for further treatment, or the size and location of the odontoma. Although the osteogenic capacity of a demineralized tooth was verified as early as 1967 by Urist and many other investigators, the cumbersome procedure, including a long demineralization time, may be less than comfortable for clinicians. A modified ultrasonic technology, with periodic negative pressure and temperature control, facilitated rapid and aseptic preparation of demineralized teeth for bone grafts. This approach reduces the demineralization time dramatically (≤80 minutes), so that the graft material can be prepared chairside on the same day as the extraction. The purpose of this article is to describe two cases of large compound odonotomas used as graft material prepared chairside for enucleation-induced bony defects. These two clinical cases showed favorable wound healing without complications, and good bony support for future dental implants or orthodontic treatment. Finally, this report will suggest the possibility of recycling the benign pathologic hard tissue as an alternative treatment option for conventional bone grafts in clinics.

  9. An alternative treatment option for a bony defect from large odontoma using recycled demineralization at chairside

    PubMed Central

    2015-01-01

    Odontoma is the most common odontogenic benign tumor, and the treatment of choice is generally surgical removal. After excision, bone grafts may be necessary depending on the need for further treatment, or the size and location of the odontoma. Although the osteogenic capacity of a demineralized tooth was verified as early as 1967 by Urist and many other investigators, the cumbersome procedure, including a long demineralization time, may be less than comfortable for clinicians. A modified ultrasonic technology, with periodic negative pressure and temperature control, facilitated rapid and aseptic preparation of demineralized teeth for bone grafts. This approach reduces the demineralization time dramatically (≤80 minutes), so that the graft material can be prepared chairside on the same day as the extraction. The purpose of this article is to describe two cases of large compound odonotomas used as graft material prepared chairside for enucleation-induced bony defects. These two clinical cases showed favorable wound healing without complications, and good bony support for future dental implants or orthodontic treatment. Finally, this report will suggest the possibility of recycling the benign pathologic hard tissue as an alternative treatment option for conventional bone grafts in clinics. PMID:25922824

  10. TMI-2 purification demineralizer resin study

    SciTech Connect

    Thompson, J D; Osterhoudt, T R

    1984-05-01

    Study of the Makeup and Purification System demineralizers at TMI-2 has established that fuel quantities in the vessels are low, precluding criticality, that the high radioactive cesium concentration on the demineralizer resins can be chemically removed, and that the demineralizer resins can probably be removed from the vessels by sluicing through existing plant piping. Radiation measurements from outside the demineralizers establishing that there is between 1.5 and 5.1 (probably 3.3) lb of fuel in the A vessel and less than that amount in the B vessel. Dose rates up to 2780 R per hour were measured on contact with the A demineralizer. Remote visual observation of the A demineralizer showed a crystalline crust overlaying amber-colored resins. The cesium activity in solid resin samples ranged from 220 to 16,900 ..mu..Ci/g. Based on this information, researchers concluded that the resins cannot be removed through the normal pathway in their present condition. Studies do show that the resins will withstand chemical processing designed to rinse and elute cesium from the resins. The process developed should work on the TMI-2 resins.

  11. DEMINERALIZER BUILDING, TRA609. CAMERA FACES NORTHEAST. BUILDING IS COMPLETE. DEMINERALIZER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DEMINERALIZER BUILDING, TRA-609. CAMERA FACES NORTHEAST. BUILDING IS COMPLETE. DEMINERALIZER STORAGE TANK TO THE RIGHT. RAW WATER STORAGE TANK BEYOND. INL NEGATIVE NO. 4771. Unknown Photographer, 4/24/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  12. Is mobilized peripheral blood comparable with bone marrow as a source of hematopoietic stem cells for allogeneic transplantation from HLA-identical sibling donors? A case-control study

    PubMed Central

    Gallardo, David; de la Cámara, Rafael; Nieto, Jose B.; Espigado, Ildefonso; Iriondo, Arturo; Jiménez-Velasco, Antonio; Vallejo, Carlos; Martín, Carmen; Caballero, Dolores; Brunet, Salut; Serrano, David; Solano, Carlos; Ribera, Josep M.; de la Rubia, Javier; Carreras, Enric

    2009-01-01

    Background Granulocyte colony-stimulating factor mobilized peripheral blood stem cells are increasingly used instead of bone marrow as a stem cell source for transplantation. Whereas this change is almost complete for autologous transplantation, there are some concerns when considering allogeneic transplants. Design and Methods We performed a retrospective case-control study including 820 adult patients who had received an allogeneic stem cell transplant from an HLA-identical sibling donor. Quality of life (QoL) was assessed in 150 patients using the EORTC Quality of Life Questionnaire C30 (QLQ-C30). Results There were no statistically significant differences in overall survival at ten years (bone marrow: 48.9% vs. peripheral blood stem cells: 39.8%; p=0.621), transplant-related mortality (bone marrow: 28.9% vs. peripheral blood stem cells: 34.4%; p=0.682) or relapse incidence at 9 years (29.4% vs. 35.2%, respectively; p=0.688). Similar outcomes were maintained independently of the phase of the disease. However, multivariate analysis identified a higher incidence of acute graft-versus-host disease grades II-IV (p: 0.023; Hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.05–1.89) and grades III-IV (p: 0.006; HR: 1.89; 95% CI: 1.20–2.98), in the peripheral blood stem cells-stem cell transplant group. As previously described, extensive chronic graft-versus-host disease was also more frequent in the peripheral blood stem cells group (28% vs. 15.6%; p<0.001). Patients transplanted with peripheral blood stem cells had significant impairment of role and social functioning. Conclusions Although overall survival was not affected by the stem cell source, peripheral blood stem cell transplants were associated with a higher risk of both acute and chronic GvHD. Global quality of life was similar in both groups, but patients transplanted with peripheral blood stem cells showed worse role and social functioning scores, probably related to the increased incidence of

  13. Mesenchymal Stromal Cells from Osteoarthritic Synovium Are a Distinct Population Compared to Their Bone-Marrow Counterparts regarding Surface Marker Distribution and Immunomodulation of Allogeneic CD4+ T-Cell Cultures

    PubMed Central

    Bucur, Florin; Moradi, Babak

    2016-01-01

    Introduction. The participation of an inflammatory joint milieu has been described in osteoarthritis (OA) pathogenesis. Mesenchymal stromal cells (MSCs) play an important role in modulating inflammatory processes. Based on previous studies in an allogeneic T-cell coculture model, we aimed at further determining the role of synovial MSCs in OA pathogenesis. Methods. Bone-marrow (BM) and synovial membrane (SM) MSCs from hip joints of late stage OA patients and CD4+ T-cells from healthy donors were analysed regarding surface marker expression before and after coculture. Proliferation upon CD3/CD28 stimulation and cytokine analyses were compared between MSCs. Results. SM-MSCs differed from BM-MSCs in several surface markers and their osteogenic differentiation potential. Cocultures of both MSCs with CD4+ T-cells resulted in recruitment of CD45RA+ FoxP3+ regulatory T-cells. Upon stimulation, only SM-MSCs suppressed CD4+ T-cell proliferation, while both SM-MSCs and BM-MSCs modified cytokine profiles through suppressing IL-2 and TNF-α as well as increasing IL-6 secretion. Conclusions. Synovial MSCs from OA joints are a unique fraction that can be distinguished from their bone-marrow derived counterparts. Their unique ability to suppress CD3/CD28 induced CD4+ T-cell proliferation makes them a potential target for future therapeutic approaches. PMID:27516777

  14. Mesenchymal Stromal Cells from Osteoarthritic Synovium Are a Distinct Population Compared to Their Bone-Marrow Counterparts regarding Surface Marker Distribution and Immunomodulation of Allogeneic CD4+ T-Cell Cultures.

    PubMed

    Hagmann, Sebastien; Rimmele, Claudia; Bucur, Florin; Dreher, Thomas; Zeifang, Felix; Moradi, Babak; Gotterbarm, Tobias

    2016-01-01

    Introduction. The participation of an inflammatory joint milieu has been described in osteoarthritis (OA) pathogenesis. Mesenchymal stromal cells (MSCs) play an important role in modulating inflammatory processes. Based on previous studies in an allogeneic T-cell coculture model, we aimed at further determining the role of synovial MSCs in OA pathogenesis. Methods. Bone-marrow (BM) and synovial membrane (SM) MSCs from hip joints of late stage OA patients and CD4+ T-cells from healthy donors were analysed regarding surface marker expression before and after coculture. Proliferation upon CD3/CD28 stimulation and cytokine analyses were compared between MSCs. Results. SM-MSCs differed from BM-MSCs in several surface markers and their osteogenic differentiation potential. Cocultures of both MSCs with CD4+ T-cells resulted in recruitment of CD45RA+ FoxP3+ regulatory T-cells. Upon stimulation, only SM-MSCs suppressed CD4+ T-cell proliferation, while both SM-MSCs and BM-MSCs modified cytokine profiles through suppressing IL-2 and TNF-α as well as increasing IL-6 secretion. Conclusions. Synovial MSCs from OA joints are a unique fraction that can be distinguished from their bone-marrow derived counterparts. Their unique ability to suppress CD3/CD28 induced CD4+ T-cell proliferation makes them a potential target for future therapeutic approaches. PMID:27516777

  15. Human histology of allogeneic block grafts for alveolar ridge augmentation: case report.

    PubMed

    Morelli, Thiago; Neiva, Rodrigo; Wang, Hom-Lay

    2009-12-01

    Autogenous bone grafts obtained from the mandibular symphysis or ramus are the primary donor sites for harvesting bone in the oral cavity to correct ridge deficiencies. Although such bone grafts can be successful, several concerns remain, such as donor site morbidity, nerve paresthesia, devitalization of natural teeth, and postoperative complications (eg, swelling, discomfort, and pain). To avoid these concerns and overcome the limited amount of autogenous intraoral bone for grafting, allogeneic block grafts were introduced. The purposes of this paper were to introduce allogeneic block grafts, demonstrate the integration of these allogeneic block grafts into the recipient site by detailed histology, and describe the step-by-step surgical technique of how this graft was used in a patient. A literature search was conducted to identify papers related to allogeneic block grafting, and papers were reviewed and summarized. The advantages and disadvantages of allogeneic block grafting were presented based on the literature and the authors' experience. One patient treated with allogeneic block graft was illustrated. The histologic evidence obtained from this patient indicated good bone remodeling and significant amount of new bone formation. The literature and clinical experience have shown that allogeneic block grafts can be used successfully to augment deficient ridges. PMID:20072743

  16. Bilateral transplantation of allogenic adult human bone marrow-derived mesenchymal stem cells into the subventricular zone of Parkinson's disease: a pilot clinical study.

    PubMed

    Venkataramana, N K; Pal, Rakhi; Rao, Shailesh A V; Naik, Arun L; Jan, Majahar; Nair, Rahul; Sanjeev, C C; Kamble, Ravindra B; Murthy, D P; Chaitanya, Krishna

    2012-01-01

    The progress of PD and its related disorders cannot be prevented with the medications available. In this study, we recruited 8 PD and 4 PD plus patients between 5 to 15 years after diagnosis. All patients received BM-MSCs bilaterally into the SVZ and were followed up for 12 months. PD patients after therapy reported a mean improvement of 17.92% during "on" and 31.21% during "off" period on the UPDRS scoring system. None of the patients increased their medication during the follow-up period. Subjectively, the patients reported clarity in speech, reduction in tremors, rigidity, and freezing attacks. The results correlated with the duration of the disease. Those patients transplanted in the early stages of the disease (less than 5 years) showed more improvement and no further disease progression than the later stages (11-15 years). However, the PD plus patients did not show any change in their clinical status after stem cell transplantation. This study demonstrates the safety of adult allogenic human BM-MSCs transplanted into the SVZ of the brain and its efficacy in early-stage PD patients. PMID:22550521

  17. Allogenous tooth fragment reattachment

    PubMed Central

    Maitin, Nitin; Maitin, Shipra; Rastogi, Khushboo; Bhushan, Rajarshi

    2013-01-01

    Coronal fractures of the anterior teeth are a common form of dental trauma and its sequelae may impair the establishment and accomplishment of an adequate treatment plan. Among the various treatment options, reattachment of a crown fragment obtained from a previously extracted tooth is a conservative treatment that should be considered for crown fractures of anterior teeth. This article reports reattachment of an allogenous tooth fragment in a fractured maxillary lateral incisor in a 38-year-old patient. It is suggested that allogenous reattachment in a fractured anterior tooth serves to be a better alternative and should be further researched. Aesthetic and functional rehabilitation of a fractured complicated anterior crown using allogenous tooth fragment is a better alternative to other more conventional treatment options. PMID:23845684

  18. The bone marrow microenvironment is similarly impaired in allogeneic hematopoietic stem cell transplantation patients with early and late poor graft function.

    PubMed

    Kong, Y; Wang, Y-T; Hu, Y; Han, W; Chang, Y-J; Zhang, X-H; Jiang, Z-F; Huang, X-J

    2016-02-01

    Poor graft function (PGF), including early and late PGF, is a serious complication following allotransplant. We recently reported that bone marrow microenvironment abnormalities may occur in cases of late PGF. Whether these abnormalities occur in early PGF remains unknown. To answer this question, we performed a nested case-control study comparing cellular elements of the bone marrow microenvironment in 10 subjects with early PGF, 30 subjects with late PGF and 40 subjects without PGF. Bone marrow endosteal cells, perivascular cells and endothelial cells were analyzed by flow cytometry and by hematoxylin-eosin and immunohistochemical staining in situ. Subjects with early and late PGF had similar abnormalities in these cell types compared with transplant recipients without PGF. However, none of the aforementioned elements of the bone marrow microenvironment were significantly different between early and late PGF patients. Our data suggest that similar abnormalities in the bone marrow microenvironment may occur in early and late PGF post allotransplant. Cellular approaches, such as the administration of mesenchymal stem cells, promise to be beneficial therapeutic strategies in patients with early or late PGF.

  19. Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report.

    PubMed

    Entz-Werle, N; Suciu, S; van der Werff ten Bosch, J; Vilmer, E; Bertrand, Y; Benoit, Y; Margueritte, G; Plouvier, E; Boutard, P; Vandecruys, E; Ferster, A; Lutz, P; Uyttebroeck, A; Hoyoux, C; Thyss, A; Rialland, X; Norton, L; Pages, M-P; Philippe, N; Otten, J; Behar, C

    2005-12-01

    The first EORTC (European Organization of Research and Treatment of Cancer) acute myeloblastic leukemia (AML) pilot study (58872) was conducted between January 1988 and December 1991. Out of 108 patients, 78% achieved complete remission (CR), and event-free survival (EFS) and survival rates (s.e., %) at 7 years were 40 (5) and 51% (6%), respectively. It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity. The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses, further therapy consisting of allogeneic bone marrow transplantation (alloBMT) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor. Out of 177 patients, recruited between October 1992 and December 2002, 81% reached CR. Overall 7-year EFS and survival rates were 49 (4) and 62% (4%), respectively. Out of 145 patients who received the first intensification, 39 had a sibling donor. In patients with or without a donor, the 7-year disease-free survival (DFS) rate was 63 (8) and 57% (5%) and the 7-year survival rate was 78 (7) and 65% (5%), respectively. Patients with favorable, intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57, 45 and 45% and a 5-year survival rate of 89, 67 and 53%, respectively.

  20. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study.

    PubMed

    Bhatia, Smita; Francisco, Liton; Carter, Andrea; Sun, Can-Lan; Baker, K Scott; Gurney, James G; McGlave, Philip B; Nademanee, Auayporn; O'Donnell, Margaret; Ramsay, Norma K C; Robison, Leslie L; Snyder, David; Stein, Anthony; Forman, Stephen J; Weisdorf, Daniel J

    2007-11-15

    We assessed late mortality in 1479 individuals who had survived 2 or more years after allogeneic hematopoietic cell transplantation (HCT). Median age at HCT was 25.9 years and median length of follow-up was 9.5 years. The conditional survival probability at 15 years from HCT was 80.2% (SE = 1.9%) for those who were disease-free at entry into the cohort, and the relative mortality was 9.9 (95% confidence interval, 8.7-11.2). Relative mortality decreased with time from HCT, but remained significantly elevated at 15 years after HCT (standardized mortality ratio = 2.2). Relapse of primary disease (29%) and chronic graft-versus-host disease (cGVHD: 22%) were the leading causes of premature death. Nonrelapse-related mortality was increased among patients older than 18 years at HCT (18-45 years: relative risk [RR] = 1.7; 46+ years: RR = 3.7) and among those with cGVHD (RR = 2.7), and was lower among patients who received methotrexate for GVHD prophylaxis (RR = 0.5). HCT survivors were more likely to report difficulty in holding jobs (odds ratio [OR] = 13.9), and in obtaining health (OR = 7.1) or life (OR = 9.9) insurance compared with siblings. This study demonstrates that mortality rates remain twice as high as that of the general population among 15-year survivors of HCT, and that the survivors face challenges affecting their health and well-being.

  1. [Kinetics of vaccine antibodies to tetanus toxoid, diphtheria toxoid, measles virus, poliomyelitis virus and pneumococci after allogenic and autologous bone marrow transplantation and booster immunization. 1: The kinetics of vaccine antibodies to tetanus toxoid after allogenic and autologous bone marrow transplantation].

    PubMed

    Prager, J; Baumert, A; Hermann, J; Fuchs, D; Zintl, F

    1992-06-01

    Today BMT belongs to the established methods of treatment in haematology and oncology. Because of the constant increase of healthy long-term survivors after BMT the problem of immunological reconstitution and eventual possible late effects gets more and more importance. One problem, which til now has been few attention paid to, is that of the protection by vaccination after BMT. We report on the kinetics of the tetanus-antitoxin in 20 patients after allogeneic or autologous BMT and demonstrate the influence of a graft-versus-host disease and its therapy on the antibody kinetics. In the group of allogeneic transplanted children without a GvHD the tetanus-antitoxin titers felt below their detection range after a time of about 8 months whereas in the group with GvHD this effect already occurred after nearly 4 months. The autologous transplanted patients have a positive antibody level til the time of 20 months after BMT. As a consequence of the lost protection by vaccination after BMT follows the necessity of revaccinations respectively of boostering after immunological reconstitution.

  2. Influence of overall treatment time in a fractionated total lymphoid irradiation as an immunosuppressive therapy in allogeneic bone marrow transplantation in mice

    SciTech Connect

    Waer, M.; Ang, K.K.; Vandeputte, M.; Van der Schueren, E.

    1982-11-01

    Three groups of C/sub 57//BL/Ka mice received total lymphoid irradiation (TLI) in a total dose of 34 Gy in three different fractionation schedules. The tolerance of all different schedules was excellent. No difference in the peripheral white blood cell and lymphocyte counts nor the degree of immunosuppression as measured by phytohaemaglutinin or concanavalin A induced blastogenesis and mixed lymphocyte reaction were observed at the end of the treatment and up to 200 days. When bone marrow transplantation was performed one day after the end of each schedule, chimerism without signs of graft versus host disease was induced in all the groups. However, from the results in a limited number of animals it seems that concentrated schedules were less effective for chimerism induction. It has been demonstrated that it is possible to reduce drastically the overall treatment time for TLI before bone marrow transplantation. Further investigations are necessary in order to determine the optimal time-dose-fractionation factors and the different perameters involved in the transplantation.

  3. Influence of overall treatment time in a fractionated total lymphoid irradiation as an immunosuppressive therapy in allogeneic bone marrow transplantation in mice

    SciTech Connect

    Waer, M.; Ang, K.K.; Vandeputte, M.; van der Schueren, E.

    1982-11-01

    Three groups of C/sub 57//BL/Ka mice received total lymphoid irradiation (TLI) in a total dose of 34 Gy in three different fractionation schedules. In the first group daily fractions of 2 Gy were given during 3 1/2 weeks. In the second group 4 to 5 fractions with 3 1/2 hr interval were given each day, thus delivering 17 fractions in 4 days. In the third group three fractions were given daily for two consecutive days and was repeated two times after 8 or 9 days interval, resulting in a total treatment time of 3 1/2 weeks. The tolerance of all different schedules was excellent. No difference in the peripheral white blood cell and lymphocyte counts nor the degree of immunosuppression as measured by phytohaemaglutinin or concanavalin A induced blastogenesis and mixed lymphocyte reaction were observed at the end of the treatment and up to 200 days. When bone marrow transplantation was performed one day after the end of each schedule, chimerism without signs of graft versus host disease was induced in all the groups. However, from the results in a limited number of animals it seems that concentrated schedules were less effective for chimerism induction. It has been demonstrated that it is possible to reduce drastically the overall treatment time for TLI before bone marrow transplantation. Further investigations are necessary in order to determine the optimal time-dose-fractionation factors and the different parameters involved in the transplantation.

  4. Allogeneic bone marrow transplantation in children with acute myelogenous leukemia in first remission. Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) and the Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO).

    PubMed

    Dini, G; Boni, L; Abla, O; Uderzo, C; Polchi, P; Locatelli, F; Di Bartolomeo, P; Arcese, W; Iori, A P; Rossetti, F

    1994-06-01

    Fifty-nine children, aged 1-15 years, with acute myelogenous leukemia (AML) received a bone marrow transplant (BMT) from an HLA-identical sibling (n = 57) or from an identical twin (n = 2), while in first remission (CR). These children represent, to the best of our knowledge, all children grafted in first CR in 11 Italian centers between 1980 and 1990. Patients were prepared with total body irradiation (TBI) plus cyclophosphamide (CY) (n = 50) or melphalan (n = 2) or with busulfan plus CY (n = 7). GVHD prophylaxis consisted of cyclosporin A (n = 48), methotrexate (n = 7) or cyclosporin and methotrexate (n = 2). Survivors have been followed for 21-137 months (median 59 months). Actuarial relapse-free survival was 58% at 66-137 months (95% confidence interval (CI) 44-72). Actuarial risk of relapse was 23% at 48 months (95% CI 10.9-34.8). Risk of non-relapse deaths was 33% in the period 1980-87 and 4% in the period 1988-90 (p = 0.02). In multivariate analysis patients with a blood cell count > 14 x 10(9)/l at diagnosis showed a lower relapse-free survival compared with patients with counts < 14 x 10(9)/l (p = 0.006). We could not detect an effect of FAB subtype, patient age, time to achieve remission or transplant-related variables, including year of BMT, on relapse-free survival. In conclusion, allogeneic marrow transplantation can achieve long-term relapse-free survival in over 50% of children with AML and should be considered as consolidation therapy if a matched sibling is available.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Polarization sensitive optical coherence tomography in equine bone

    NASA Astrophysics Data System (ADS)

    Jacobs, J. W.; Matcher, S. J.

    2009-02-01

    Optical coherence tomography (OCT) has been used to image equine bone samples. OCT and polarization sensitive OCT (PS-OCT) images of equine bone samples, before and after demineralization, are presented. Using a novel approach, taking a series of images at different angles of illumination, the polar angle and true birefringence of collagen within the tissue is determined, at one site in the sample. The images were taken before and after the bones were passed through a demineralization process. The images show an improvement in depth penetration after demineralization allowing better visualization of the internal structure of the bone and the optical orientation of the collagen. A quantitative measurement of true birefringence has been made of the bone; true birefringence was shown to be 1.9x10-3 before demineralization increasing to 2.7x10-3 after demineralization. However, determined collagen fiber orientation remains the same before and after demineralization. The study of bone is extensive within the field of tissue engineering where an understanding of the internal structures is essential. OCT in bone, and improved depth penetration through demineralization, offers a useful approach to bone analysis.

  6. Analysis of cytokine production and V beta T-cell receptor subsets in irradiated recipients receiving portal or peripheral venous reconstitution with allogeneic bone marrow cells, with or without additional anti-cytokine monoclonal antibodies.

    PubMed Central

    Gorczynski, R M; Chen, Z; Zeng, H; Gorczynski, L; Terzioglu, E

    1998-01-01

    in the liver. Infusion of anti-IL-12 monoclonal antibodies into irradiated mice receiving i.v. cell reconstitution produced a similar pattern of changes to those seen after p.v. reconstitution, while a combination of anti-IL-10 and anti-TGF-beta monoclonal antibodies reversed the changes seen after p.v. reconstitution. These data are consistent with an important role for differential cytokine production in the regulation of GVHD following allogeneic bone marrow transplantation. PMID:9616372

  7. Cross-dressing by donor dendritic cells after allogeneic bone marrow transplantation contributes to formation of the immunological synapse and maximizes responses to indirectly presented antigen.

    PubMed

    Markey, Kate A; Koyama, Motoko; Gartlan, Kate H; Leveque, Lucie; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; MacDonald, Kelli P A; Hill, Geoffrey R

    2014-06-01

    The stimulation of naive donor T cells by recipient alloantigen is central to the pathogenesis of graft-versus-host disease after bone marrow transplantation (BMT). Using mouse models of transplantation, we have observed that donor cells become "cross-dressed" in very high levels of recipient hematopoietic cell-derived MHC class I and II molecules following BMT. Recipient-type MHC is transiently present on donor dendritic cells (DCs) after BMT in the setting of myeloablative conditioning but is persistent after nonmyeloablative conditioning, in which recipient hematopoietic cells remain in high numbers. Despite the high level of recipient-derived alloantigen present on the surface of donor DCs, donor T cell proliferative responses are generated only in response to processed recipient alloantigen presented via the indirect pathway and not in response to cross-dressed MHC. Assays in which exogenous peptide is added to cross-dressed MHC in the presence of naive TCR transgenic T cells specific to the MHC class II-peptide combination confirm that cross-dressed APC cannot induce T cell proliferation in isolation. Despite failure to induce T cell proliferation, cross-dressing by donor DCs contributes to generation of the immunological synapse between DCs and CD4 T cells, and this is required for maximal responses induced by classical indirectly presented alloantigen. We conclude that the process of cross-dressing by donor DCs serves as an efficient alternative pathway for the acquisition of recipient alloantigen and that once acquired, this cross-dressed MHC can assist in immune synapse formation prior to the induction of full T cell proliferative responses by concurrent indirect Ag presentation.

  8. Contrasting effects of anti-Ly49A due to MHC class I cis-binding on NK cell mediated allogeneic bone marrow cell resistance

    PubMed Central

    Alvarez, Maite; Sungur, Can M.; Ames, Erik; Anderson, Stephen K.; Pomeroy, Claire; Murphy, William J.

    2013-01-01

    NK subsets have activating and inhibitory receptors that bind MHC-I. Ly49A is a mouse inhibitory receptor that binds with high affinity to H2d in both a cis- and trans-manner. Ly49A cis-associations limit trans-interactions with H2d-expressing targets as well as monoclonal antibody (mAb)-binding. We demonstrate that cis-interactions affect mAb effector functions. In vivo administration of anti-Ly49A depleted NK cells in H2b but not H2d mice. Despite lack of depletion, in vivo treatment with anti-Ly49A reduced NK killing capabilities and inhibited activation, partially due to its agonistic effect. These data explain the previously described in vivo effects on bone marrow allograft rejection observed with anti-Ly49A treatment in H2d-haplotype mice. However, prior treatment of mice with poly(I:C) or MCMV infection resulted in increased Ly49A expression and Ly49A+ NK cell depletion in H2d mice. These data indicate that although Ly49 mAbs can exert similar in vivo effects in mice with different MHC-haplotypes, these effects are mediated via different mechanisms of action correlating with Ly49A expression levels and can be altered within the same strain contingent on stimuli. This illustrates the marked diversity of mAb effector functions due to the regulation of the level of expression of target antigens and responses by stimulatory incidents such as infection. PMID:23752612

  9. 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 bone ...

  10. Reconstruction of Beagle Hemi-Mandibular Defects with Allogenic Mandibular Scaffolds and Autologous Mesenchymal Stem Cells

    PubMed Central

    Luo, JinChao; Liu, HuaWei; Hu, Min; Yue, Wen

    2014-01-01

    Objective Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs) can increase the integration of massive allografts (hemi-mandible) in a large animal model. Methods Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at4 (n = 4), 12 (n = 4), 24 (n = 4) or 48 weeks (n = 3) postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD) of transplants were used to evaluate defect reconstruction outcomes. Results Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05), and all micro-architectural parameters were significantly different between groups (p<0.05). Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed. Conclusions Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a

  11. Remineralization of demineralized enamel via calcium phosphate nanocomposite.

    PubMed

    Weir, M D; Chow, L C; Xu, H H K

    2012-10-01

    Secondary caries remains the main problem limiting the longevity of composite restorations. The objective of this study was to investigate the remineralization of demineralized human enamel in vitro via a nanocomposite containing nanoparticles of amorphous calcium phosphate (NACP). NACP were synthesized by a spray-drying technique and incorporated into a dental resin. First, caries-like subsurface enamel lesions were created via an acidic solution. Then, NACP nanocomposite or a commercial fluoride-releasing control composite was placed on the demineralized enamel, along with control enamel without a composite. These specimens were then treated with a cyclic demineralization/remineralization regimen for 30 days. Quantitative microradiography showed typical enamel subsurface demineralization before cyclic demineralization/remineralization treatment, and significant remineralization in enamel under the NACP nanocomposite after the demineralization/remineralization treatment. The NACP nanocomposite had the highest enamel remineralization (mean ± SD; n = 6) of 21.8 ± 3.7%, significantly higher than the 5.7 ± 6.9% for fluoride-releasing composite (p < 0.05). The enamel group without composite had further demineralization of -26.1 ± 16.2%. In conclusion, a novel NACP nanocomposite was effective in remineralizing enamel lesions in vitro. Its enamel remineralization was 4-fold that of a fluoride-releasing composite control. Combined with the good mechanical and acid-neutralization properties reported earlier, the new NACP nanocomposite is promising for remineralization of demineralized tooth structures. PMID:22933607

  12. Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood acute lymphoblastic leukaemia in first remission. Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) and the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

    PubMed

    Uderzo, C; Valsecchi, M G; Balduzzi, A; Dini, G; Miniero, R; Locatelli, F; Rondelli, R; Pession, A; Arcese, W; Bacigalupo, A; Polchi, P; Andolina, M; Messina, C; Conter, V; Aricó, M; Galimberti, S; Masera, G

    1997-02-01

    We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study. All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation (n = 25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59-3.24), 0.69 (CI 0.27-1.77) and 0.35 (CI 0.06-1.91), with an overall non-significant difference between the two groups (P = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR). The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.

  13. Mechanical Properties of Mineralized Collagen Fibrils As Influenced By Demineralization

    SciTech Connect

    Balooch, M.; Habelitz, S.; Kinney, J.H.; Marshall, S.J.; Marshall, G.W.

    2009-05-11

    Dentin and bone derive their mechanical properties from a complex arrangement of collagen type-I fibrils reinforced with nanocrystalline apatite mineral in extra- and intrafibrillar compartments. While mechanical properties have been determined for the bulk of the mineralized tissue, information on the mechanics of the individual fibril is limited. Here, atomic force microscopy was used on individual collagen fibrils to study structural and mechanical changes during acid etching. The characteristic 67 nm periodicity of gap zones was not observed on the mineralized fibril, but became apparent and increasingly pronounced with continuous demineralization. AFM-nanoindentation showed a decrease in modulus from 1.5 GPa to 50 MPa during acid etching of individual collagen fibrils and revealed that the modulus profile followed the axial periodicity. The nanomechanical data, Raman spectroscopy and SAXS support the hypothesis that intrafibrillar mineral etches at a substantially slower rate than the extrafibrillar mineral. These findings are relevant for understanding the biomechanics and design principles of calcified tissues derived from collagen matrices.

  14. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  15. Demineralization of drinking water: Is it prudent?

    PubMed

    Verma, K C; Kushwaha, A S

    2014-10-01

    Water is the elixir of life. The requirement of water for very existence of life and preservation of health has driven man to devise methods for maintaining its purity and wholesomeness. The water can get contaminated, polluted and become a potential hazard to human health. Water in its purest form devoid of natural minerals can also be the other end of spectrum where health could be adversely affected. Limited availability of fresh water and increased requirements has led to an increased usage of personal, domestic and commercial methods of purification of water. Desalination of saline water where fresh water is in limited supply has led to development of the latest technology of reverse osmosis but is it going to be safe to use such demineralized water over a long duration needs to be debated and discussed.

  16. Laser Application in Prevention of Demineralization in Orthodontic Treatment

    PubMed Central

    Sadr Haghighi, Hooman; Skandarinejad, Mahsa; Abdollahi, Amir Ardalan

    2013-01-01

    One common negative side effect of orthodontic treatment with fixed appliances is the development of incipient caries lesions around brackets, particularly in patients with poor oral hygiene. Different methods have been used to prevent demineralization such as fluoride therapy and application of sealant to prevent caries. The recent effort to improve the resistance against the demineralization is by the application of different types of lasers. The purpose of this review article is discussing the effects of laser in prevention of demineralization in orthodontic patients. PMID:25606317

  17. Comparative study of the osteoinductive properties of bioceramic, coral and processed bone graft substitutes.

    PubMed

    Begley, C T; Doherty, M J; Mollan, R A; Wilson, D J

    1995-10-01

    This study compared the osteoinductive properties of six different bone graft substitutes: Pyrost, natural coral, Callopat, Surgibone, demineralized Surgibone and demineralized rat bone. The materials were implanted heterotopically, in the abdominal musculature of rats, and the results evaluated histologically at 3 and 6 wk post-implantation. Surprisingly, the results showed that both the demineralized rat bone and demineralized Surgibone were less osteoinductive than might be believed from the literature. Mineralized grafts showed no sign of new bone formation and exhibited variable resorption patterns. A layer of what appeared as dense calcification was seen around the coral implant. The most intense inflammatory reactions were exhibited with the xenografts Surgibone and demineralized Surgibone, indicating persistent immune responses. Coral and Pyrost elicited no marked inflammatory response, and this was attributed to the negligible amounts of protein present in these materials.

  18. Repair of segmental load-bearing bone defect by autologous mesenchymal stem cells and plasma-derived fibrin impregnated ceramic block results in early recovery of limb function.

    PubMed

    Ng, Min Hwei; Duski, Suryasmi; Tan, Kok Keong; Yusof, Mohd Reusmaazran; Low, Kiat Cheong; Rose, Isa Mohamed; Mohamed, Zahiah; Bin Saim, Aminuddin; Idrus, Ruszymah Bt Hj

    2014-01-01

    Calcium phosphate-based bone substitutes have not been used to repair load-bearing bone defects due to their weak mechanical property. In this study, we reevaluated the functional outcomes of combining ceramic block with osteogenic-induced mesenchymal stem cells and platelet-rich plasma (TEB) to repair critical-sized segmental tibial defect. Comparisons were made with fresh marrow-impregnated ceramic block (MIC) and partially demineralized allogeneic bone block (ALLO). Six New Zealand White female rabbits were used in each study group and three rabbits with no implants were used as negative controls. By Day 90, 4/6 rabbits in TEB group and 2/6 in ALLO and MIC groups resumed normal gait pattern. Union was achieved significantly faster in TEB group with a radiological score of 4.50 ± 0.78 versus ALLO (1.06 ± 0.32), MIC (1.28 ± 0.24), and negative controls (0). Histologically, TEB group scored the highest percentage of new bone (82% ± 5.1%) compared to ALLO (5% ± 2.5%) and MIC (26% ± 5.2%). Biomechanically, TEB-treated tibiae achieved the highest compressive strength (43.50 ± 12.72 MPa) compared to those treated with ALLO (15.15 ± 3.57 MPa) and MIC (23.28 ± 6.14 MPa). In conclusion, TEB can repair critical-sized segmental load-bearing bone defects and restore limb function.

  19. Surface structure and biocompatibility of demineralized dentin matrix granules soaked in a simulated body fluid

    NASA Astrophysics Data System (ADS)

    Akazawa, Toshiyuki; Murata, Masaru; Hino, Jun; Nagano, Futami; Shigyo, Tatsuhiro; Nomura, Takafumi; Inano, Hiroyuki; Itabashi, Kohji; Yamagishi, Tohru; Nakamura, Katsuo; Takahashi, Touru; Iida, Shunji; Kashiwazaki, Haruhiko

    2012-12-01

    Demineralized dentin matrix (DDM) granules with excellent biocompatibility were easily prepared using unnecessary human teeth by a new cooling-pulverizing and demineralizing technique. Extracted human teeth were pulverized together with saline ice at 12,000 rpm-rotation number of a ZrO2 blade for 30 s in a ZrO2 vessel. The pulverized granules exhibited the particle size distribution of 0.5-2 mm that was efficient for regeneration of alveolar bone. The (Ca/P) ratios of the granules were 1.60-1.66, which were close to the stoichiometric value of 1.67 for standard hydroxyapatite (HAp). Small amounts of Na+ and Mg2+ ions present at less than 1% were detected. The pulverized granules were dissolved with stirring under 500 rpm for 10-60 min in 2.0%-HNO3 solutions to obtain partial or complete DDM granules. As the dissolution time increased, crystallinity of HAp phase lowered and asperity on surfaces of the granules became outstanding due to elution of mineral components. At the dissolution of 60 min, the pulverizing granules were completely demineralized and the weight decreased to about one-fifth. To improve surface activity of the DDM granules without denaturation of bone growth factors, the DDM granules were soaked at 309.5 K and pH 7.40 in a simulated body fluid (SBF). HAp microcrystals were gradually precipitated on surfaces of the DDM granules with increasing the soaking time. Different morphology of the precipitates was observed, depending on the demineralization situation of the pulverized granules. For the DDM with low dissolution efficiency of 42%, porous bone-like apatites at 24 h after the soaking and fiber-oriented aggregates at 144 h were recognized. The bioactive DDM granules were implanted into the subcutaneous tissues of the back region of rats. At 4 weeks after the implantation, bio-absorption by comparatively small amounts of multi-giant cells was recognized around the surface layers of DDM granules.

  20. Peripheral blood CD5-positive B lymphocytes (B-1a cells) after allogeneic stem cell transplantation for acute myeloid leukaemia in humans

    PubMed Central

    Veneri, Dino; Franchini, Massimo; de Sabata, Donata; Ledro, Silvia; Vella, Antonio; Ortolani, Riccardo; Pizzolo, Giovanni; Benedetti, Fabio

    2008-01-01

    Background Only few data are available in literature regarding the reconstitution of B-1a cells after allogeneic bone marrow transplantation performed for haematological malignancies. Methods In this study we used flow cytometry to assess the reconstitution of the peripheral blood B-1a cell compartment after allogeneic peripheral blood stem cell transplantation. Cytometric analyses were performed over time on 11 consecutive patients undergoing allogeneic peripheral blood stem cell transplantation for acute myeloid leukaemia in our Haematology Unit and the results were compared with available data regarding B-1a cell reconstitution after allogeneic bone marrow stem cell transplantation. Results In spite of an earlier recovery of B-1a cells in the peripheral blood after allogeneic bone marrow transplantation, the reconstitution of this B-cell subset was similar, regardless of the source of stem cells employed. Conclusions Further studies are necessary in order to clarify the origin of B-1a cells in humans in health and illness. PMID:19112737

  1. Allogeneic Marrow Transplantation in Patients With Severe Systemic Sclerosis

    PubMed Central

    Nash, Richard A.; McSweeney, Peter A.; Nelson, J. Lee; Wener, Mark; Georges, George E.; Langston, Amelia A.; Shulman, Howard; Sullivan, Keith M.; Lee, Julie; Henstorf, Gretchen; Storb, Rainer; Furst, Daniel E.

    2010-01-01

    Objective To evaluate the safety and efficacy of allogeneic hematopoietic cell transplantation (HCT) after myeloablative conditioning in patients with severe systemic sclerosis (SSc). Methods Eligibility criteria for the study included SSc patients with features indicative of a poor prognosis. The myeloablative conditioning regimen included busulfan, cyclophosphamide, and antithymocyte globulin. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and methotrexate. Bone marrow was transplanted from HLA-identical siblings. Results Two patients with diffuse cutaneous SSc and lung involvement who were refractory to conventional immunosuppressive treatment were enrolled in the study. In patient 1, there were no complications related to the conditioning regimen, and GVHD did not develop after transplantation. At 5 years after HCT, there was nearly complete resolution of the scleroderma and marked improvement in physical functioning. Internal organ function improved (lung) or remained stable. On examination of serial skin biopsy samples, there was resolution of the dermal fibrosis. Patient 2 experienced skin toxicity from the conditioning regimen and hypertensive crisis that was likely related to high-dose corticosteroids given for treatment of GVHD. Although this patient experienced an improvement in scleroderma and overall functioning, a fatal opportunistic infection developed 17 months after HCT. Conclusion Allogeneic HCT may result in sustained remission of SSc. GVHD and opportunistic infections are the major risks associated with allogeneic HCT for SSc, as for allogeneic HCT in general. PMID:16732546

  2. Demineralization Depth Using QLF and a Novel Image Processing Software.

    PubMed

    Wu, Jun; Donly, Zachary R; Donly, Kevin J; Hackmyer, Steven

    2010-01-01

    Quantitative Light-Induced fluorescence (QLF) has been widely used to detect tooth demineralization indicated by fluorescence loss with respect to surrounding sound enamel. The correlation between fluorescence loss and demineralization depth is not fully understood. The purpose of this project was to study this correlation to estimate demineralization depth. Extracted teeth were collected. Artificial caries-like lesions were created and imaged with QLF. Novel image processing software was developed to measure the largest percent of fluorescence loss in the region of interest. All teeth were then sectioned and imaged by polarized light microscopy. The largest depth of demineralization was measured by NIH ImageJ software. The statistical linear regression method was applied to analyze these data. The linear regression model was Y = 0.32X + 0.17, where X was the percent loss of fluorescence and Y was the depth of demineralization. The correlation coefficient was 0.9696. The two-tailed t-test for coefficient was 7.93, indicating the P-value = .0014. The F test for the entire model was 62.86, which shows the P-value = .0013. The results indicated statistically significant linear correlation between the percent loss of fluorescence and depth of the enamel demineralization.

  3. Demineralization Depth Using QLF and a Novel Image Processing Software

    PubMed Central

    Wu, Jun; Donly, Zachary R.; Donly, Kevin J.; Hackmyer, Steven

    2010-01-01

    Quantitative Light-Induced fluorescence (QLF) has been widely used to detect tooth demineralization indicated by fluorescence loss with respect to surrounding sound enamel. The correlation between fluorescence loss and demineralization depth is not fully understood. The purpose of this project was to study this correlation to estimate demineralization depth. Extracted teeth were collected. Artificial caries-like lesions were created and imaged with QLF. Novel image processing software was developed to measure the largest percent of fluorescence loss in the region of interest. All teeth were then sectioned and imaged by polarized light microscopy. The largest depth of demineralization was measured by NIH ImageJ software. The statistical linear regression method was applied to analyze these data. The linear regression model was Y = 0.32X + 0.17, where X was the percent loss of fluorescence and Y was the depth of demineralization. The correlation coefficient was 0.9696. The two-tailed t-test for coefficient was 7.93, indicating the P-value = .0014. The F test for the entire model was 62.86, which shows the P-value = .0013. The results indicated statistically significant linear correlation between the percent loss of fluorescence and depth of the enamel demineralization. PMID:20445755

  4. Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

    PubMed Central

    Bensinger, William I.

    2007-01-01

    Despite significant improvements in survival for multiple myeloma patients through autologous stem-cell transplantation (SCT) and the introduction of novel drugs, the disease remains incurable for all but a small fraction of patients. Only allogeneic SCT is potentially curative, due in part to a graft-versus-myeloma effect. High transplant-related mortality with allogeneic SCT is currently the major limitation to wider use of this potentially curative modality. Mortality can be reduced through the use of lower-intensity conditioning regimens which allow engraftment of allogeneic stem cells, but this comes at a cost of higher rates of disease progression and relapse. Promising studies to improve outcomes of allogeneic transplants include the use of more intensive non-myeloablative conditioning regimens, tandem transplants, peripheral blood cells, graft engineering to improve the graft-versus-myeloma activity while reducing graft-versus-host disease (GVHD), post-transplant maintenance, and targeted conditioning therapies such as bone-seeking radioisotopes. PMID:18070719

  5. Nonmyeloablative allogeneic hematopoietic cell transplantation

    PubMed Central

    Storb, Rainer; Sandmaier, Brenda M.

    2016-01-01

    Most hematological malignancies occur in older patients. Until recently these patients and those with comorbidities were not candidates for treatment with allogeneic hematopoietic transplantation because they were unable to tolerate the heretofore used high-dose conditioning regimens. The finding that many of the cures achieved with allogeneic hematopoietic transplantation were due to graft-versus-tumor effects led to the development of less toxic and well-tolerated reduced intensity and nonmyeloablative regimens. These regimens enabled allogeneic engraftment, thereby setting the stage for graft-versus-tumor effects. This review summarizes the encouraging early results seen with the new regimens and discusses the two hurdles that need to be overcome for achieving even greater success, disease relapse and graft-versus-host disease. PMID:27132278

  6. Proanthocyanidins Rapidly Stabilize the Demineralized Dentin Layer

    PubMed Central

    Liu, Y.; Dusevich, V.; Wang, Y.

    2013-01-01

    While proanthocyanidins (PA) are effective in improving collagen’s resistance to collagenolytic degradation, the direct incorporation of PA into an adhesive system is detrimental to the light-curing thereof. Conversely, the use of PA as a primer could circumvent this issue, but little is known about the efficacy of PA in stabilizing collagen when applied in a clinically relevant manner. This study investigated the pre- and post-digestion morphology of an acid-etched dentin collagen layer that underwent PA treatment for time periods on a scale of seconds. The null hypothesis, that there is no difference between the PA-treated and untreated control group, had to be rejected, since it was revealed that the untreated control could not survive 1 hr of exogenous collagenase digestion, while the PA-treated collagen could sustain at least 16 hrs of digestion with no perceptible changes in collagen structure. In addition, the stabilizing effect of the gold-standard cross-linker glutaraldehyde at comparable experimental conditions was found to be almost non-existent within the 5, 15, or 30 sec of cross-linking permitted. Therefore, PA have been proven to be extraordinarily efficient in stabilizing demineralized dentin collagen against enzymatic challenges in a clinically relevant setting, likely due to the non-covalent nature of their interaction with collagen molecules. PMID:23723381

  7. Comparison of three lasers on demineralization of human enamel

    NASA Astrophysics Data System (ADS)

    Powell, G. L.; Yu, Duncan; Higuchi, William I.; Fox, Jeffrey L.

    1993-07-01

    Previous studies have recorded the reduction of caries-like lesions or demineralization in extracted human teeth that had been irradiated with CO2 laser, Nd:YAG laser, and Argon laser. This study was conducted to evaluate the effects of three different cw lasers on acid resistance and demineralization of dental enamel. Human enamel was laser irradiated with either Argon, CO2, or Nd:YAG energy densities of 60 - 65 J/cm2 or 120 - 130 J/cm2. The amount of demineralization was determined in a rotating disk assembly (0.1 M acetate buffer, pH - 4.5) for 24 hours and the results determined and plotted against the non-lased control using microradiographs and computerized imaging. The amount of dissolution of tooth structure lost to demineralization in 4.5 pH acid bath in a 24 hour period was reduced from approximately 140 microns for the unlased control to approximately 90 microns for the Argon laser and 70 microns for the CO2 laser at 60 - 65 J/cm2. At 120 - 130 J/cm2 the results were: 120 microns for the Nd:YAG, 70 microns for the Argon, and 45 microns for the CO2 laser. This study shows that demineralization is reduced significantly in vitro when human enamel is exposed to Argon and CO2 laser irradiation.

  8. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses.

    PubMed

    Owens, Sean D; Kol, Amir; Walker, Naomi J; Borjesson, Dori L

    2016-01-01

    Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs) injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM) or adipose tissue derived MSCs (ad-MSCs) were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89%) were positive for anti-bovine serum albumin (BSA) antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection. PMID:27648075

  9. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

    PubMed Central

    2016-01-01

    Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs) injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM) or adipose tissue derived MSCs (ad-MSCs) were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89%) were positive for anti-bovine serum albumin (BSA) antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection. PMID:27648075

  10. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

    PubMed Central

    2016-01-01

    Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs) injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM) or adipose tissue derived MSCs (ad-MSCs) were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89%) were positive for anti-bovine serum albumin (BSA) antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection.

  11. Superior osteogenesis in transplanted allogeneic canine skull following chemical sterilization

    SciTech Connect

    Prolo, D.J.; Pedrotti, P.W.; Burres, K.P.; Oklund, S.

    1982-08-01

    Sterilization of allogeneic bone increases the availability of this tissue for supplanting skeletal defects and effecting fusions. The optimal sterilant destroys micro-organisms, preserves the physical and chemical integrity of bone and possibly even reduces immunogenicity. Cortical bone of skull heals slowly and is variably resorbed. Of 36 dogs, spontaneous regeneration in 72 paired 20 mm defects was constant but always incomplete, and restored only about one third of the cross-sectional area of the defect at six months. The repair in defects replaced with canine allogeneic bony disc, sterilized with ethylene oxide (n . 9), gamma irradiation (n . 7), or methanol/chloroform/iodoacetic acid (n . 7) and then lyophilizedd, was compared with repair in defects filled with aseptically procured lyophilized only (n . 23) discs from the same donor. Criteria for evaluation of implants at six months included volume of defect filled, radiodensity, extent of fusion around circumference, revascularization, and remodeling. Bony discs sterilized with methanol/chloroform/iodoacetic acid remodeled at a superior rate (p less than 0.01). Radiation sterilization resulted in diminished density and inferentially reduced protection of the brain (p less than 0.025). Ethylene oxide, lyophilized implants, and implants lyophilized only produced comparable repair. Whereas an acceptable cranioplasty was achieved in 86% of methanol/chloroform/iodoacetic acid, lyophilize implants, all other alloimplants served an osteoconductive function with a successful repair occurring in 56% to 58%.

  12. Gut microbiota and allogeneic transplantation.

    PubMed

    Wang, Weilin; Xu, Shaoyan; Ren, Zhigang; Jiang, Jianwen; Zheng, Shusen

    2015-08-23

    The latest high-throughput sequencing technologies show that there are more than 1000 types of microbiota in the human gut. These microbes are not only important to maintain human health, but also closely related to the occurrence and development of various diseases. With the development of transplantation technologies, allogeneic transplantation has become an effective therapy for a variety of end-stage diseases. However, complications after transplantation still restrict its further development. Post-transplantation complications are closely associated with a host's immune system. There is also an interaction between a person's gut microbiota and immune system. Recently, animal and human studies have shown that gut microbial populations and diversity are altered after allogeneic transplantations, such as liver transplantation (LT), small bowel transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell transplantation (HTCT). Moreover, when complications, such as infection, rejection and graft versus host disease (GVHD) occur, gut microbial populations and diversity present a significant dysbiosis. Several animal and clinical studies have demonstrated that taking probiotics and prebiotics can effectively regulate gut microbiota and reduce the incidence of complications after transplantation. However, the role of intestinal decontamination in allogeneic transplantation is controversial. This paper reviews gut microbial status after transplantation and its relationship with complications. The role of intervention methods, including antibiotics, probiotics and prebiotics, in complications after transplantation are also discussed. Further research in this new field needs to determine the definite relationship between gut microbial dysbiosis and complications after transplantation. Additionally, further research examining gut microbial intervention methods to ameliorate complications after transplantation is warranted. A better understanding of the

  13. Family 2 cystatins inhibit osteoclast-mediated bone resorption in calvarial bone explants.

    PubMed

    Brand, H S; Lerner, U H; Grubb, A; Beertsen, W; Nieuw Amerongen, A V; Everts, V

    2004-09-01

    Osteoclastic bone resorption depends on the activity of various proteolytic enzymes, in particular those belonging to the group of cysteine proteinases. Biochemical studies have shown that cystatins, naturally occurring inhibitors of these enzymes, inhibit bone matrix degradation. Since the mechanism by which cystatins exert this inhibitory effect is not completely resolved yet, we studied the effect of cystatins on bone resorption microscopically and by Ca-release measurements. Calvarial bone explants were cultured in the presence or absence of family 2 cystatins and processed for light and electron microscopic analysis, and the culture media were analyzed for calcium release. Both egg white cystatin and human cystatin C decreased calcium release into the medium significantly. Microscopic analyses of the bone explants demonstrated that in the presence of either inhibitor, a high percentage of osteoclasts was associated with demineralized non-degraded bone matrix. Following a 24-h incubation in the presence of cystatin C, 41% of the cells were adjacent to areas of demineralized non-degraded bone matrix, whereas in controls, this was only 6%. If bone explants were cultured with both PTH and cystatin C, 60% of the osteoclasts were associated with demineralized non-degraded bone matrix, compared to 27% for bones treated with PTH only (P < 0.01). Our study provides evidence that cystatins, the naturally occurring inhibitors of cysteine proteinases, reversibly inhibit bone matrix degradation in the resorption lacunae adjacent to osteoclasts. These findings suggest the involvement of cystatins in the modulation of osteoclastic bone degradation.

  14. Argon laser effect on demineralization of human enamel

    NASA Astrophysics Data System (ADS)

    Powell, G. L.; Higuchi, William I.; Fox, Jeffrey L.; Yu, Duncan; Blankenau, Richard J.

    1992-06-01

    Previous studies have recorded the reduction of caries-like lesions in extracted human teeth that have been irradiated with CO2 laser. Other studies have shown a decrease in dissolution rate of enamel that has been irradiated with CO2 laser and acid resistance. This study was conducted to evaluate the effects of Argon laser irradiation on acid resistance and demineralization of dental enamel. Human enamel was laser irradiated with approximately 60 J/cm2 and 120 J/cm2. The amount of demineralization was determined in a rotating disk assembly (0.1 M acetate buffer, pH-4.5) for 24 hours and the results determined and plotted against the nonlased control using microradiographs and computerized imaging. The amount of dissolution of tooth structure lost to demineralization in 4.5 pH acid bath in a 24 hour period was reduced from approximately 140 micrometers to approximately 70 micrometers . This study show that demineralization is reduced when human enamel is exposed to Argon laser irradiation.

  15. Mixed allogeneic reconstitution (A+B----A) to induce donor-specific transplantation tolerance. Permanent acceptance of a simultaneous donor skin graft

    SciTech Connect

    Ildstad, S.T.; Wren, S.M.; Oh, E.; Hronakes, M.L. )

    1991-06-01

    Mixed allogeneic reconstitution, in which a mixture of T-cell-depleted bone marrow of syngeneic host and allogeneic donor type is transplanted into a lethally irradiated recipient (A+B----A), results in mixed lymphopoietic chimerism with engraftment of a mixture of both host and donor bone marrow elements. Recipients are specifically tolerant to donor both in vitro and in vivo. Donor-specific skin grafts survive indefinitely when they are placed after full bone marrow repopulation at 28 days, while third-party grafts are rapidly rejected. To determine whether a delay of a month or more for full bone marrow repopulation is required before a donor-specific graft can be placed, we have now examined whether tolerance induction can be achieved if a graft is placed at the time of bone marrow transplantation. Permanent acceptance of donor-specific B10.BR skin grafts occurred when mixed allogeneic chimerism (B10+B10.BR----B10) was induced and a simultaneous allogeneic donor graft placed. In vitro, mixed reconstituted recipients were specifically tolerant to the B10.BR donor lymphoid cells but fully reactive to MHC-disparate third-party (BALB/c; H-2dd) when assessed by mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. These data therefore indicate that a donor-specific graft placed at the time of mixed allogeneic reconstitution is permanently accepted without rejection. To determine whether an allogeneic skin graft alone without allogeneic bone marrow would be sufficient to induce tolerance, syngeneic reconstitution (B10----B10) was carried out, and a simultaneous B10.BR allogeneic skin graft placed. Although skin grafts were prolonged in all recipients, all grafts rejected when full lymphopoietic repopulation occurred at 28 days.

  16. Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis

    NASA Technical Reports Server (NTRS)

    Pennline, James A.; Werner, Christopher R.; Lewandowski, Beth; Thompson, Bill; Sibonga, Jean; Mulugeta, Lealem

    2015-01-01

    Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

  17. Metabolic bone disease in gut diseases.

    PubMed

    Lipkin, E W

    1998-06-01

    A wide spectrum of gastrointestinal illnesses impairs bone health and can result in bone pain, demineralization, and fracture. This article summarizes current knowledge of the skeletal pathology exhibited in patients with diseases of the liver, biliary tree, pancreas, and bowel. Mechanisms responsible for these syndromes and treatment options are discussed. This article enhances the practicing gastroenterologist's knowledge of the implications of gastrointestinal illness for bone. PMID:9650030

  18. Biomimetic silicification of demineralized hierarchical collagenous tissues

    PubMed Central

    Ryou, Heonjune; Diogenes, Anibal; Yiu, Cynthia K.Y.; Mazzoni, Annalisa; Chen, Ji-hua; Arola, Dwayne D.; Hargreaves, Kenneth M.; Pashley, David H.; Tay, Franklin R.

    2013-01-01

    Unlike man-made composite materials, natural biominerals containing composites usually demonstrate different levels of sophisticated hierarchical structures which are responsible for their mechanical properties and other metabolic functions. However, the complex spatial organizations of the organic-inorganic phases are far beyond what they be achieved by contemporary engineering techniques. Here, we demonstrate that carbonated apatite present in collagen matrices derived from fish scale and bovine bone may be replaced by amorphous silica, using an approach that simulates what is utilized by phylogenetically ancient glass sponges. The structural hierarchy of these collagen-based biomaterials is replicated by the infiltration and condensation of fluidic polymer-stabilized silicic acid precursors within the intrafibrillar milieu of type I collagen fibrils. This facile biomimetic silicification strategy may be used for fabricating silica-based, three-dimensional functional materials with specific morphological and hierarchical requirements. PMID:23586938

  19. Biomimetic silicification of demineralized hierarchical collagenous tissues.

    PubMed

    Niu, Li-na; Jiao, Kai; Ryou, Heonjune; Diogenes, Anibal; Yiu, Cynthia K Y; Mazzoni, Annalisa; Chen, Ji-hua; Arola, Dwayne D; Hargreaves, Kenneth M; Pashley, David H; Tay, Franklin R

    2013-05-13

    Unlike man-made composite materials, natural biominerals containing composites usually demonstrate different levels of sophisticated hierarchical structures which are responsible for their mechanical properties and other metabolic functions. However, the complex spatial organizations of the organic-inorganic phases are far beyond what they achieved by contemporary engineering techniques. Here, we demonstrate that carbonated apatite present in collagen matrices derived from fish scale and bovine bone may be replaced by amorphous silica, using an approach that simulates what is utilized by phylogenetically ancient glass sponges. The structural hierarchy of these collagen-based biomaterials is replicated by the infiltration and condensation of fluidic polymer-stabilized silicic acid precursors within the intrafibrillar milieu of type I collagen fibrils. This facile biomimetic silicification strategy may be used for fabricating silica-based, three-dimensional functional materials with specific morphological and hierarchical requirements.

  20. Allogeneic T cell responses are regulated by a specific miRNA-mRNA network

    PubMed Central

    Sun, Yaping; Tawara, Isao; Zhao, Meng; Qin, Zhaohui S.; Toubai, Tomomi; Mathewson, Nathan; Tamaki, Hiroya; Nieves, Evelyn; Chinnaiyan, Arul M.; Reddy, Pavan

    2013-01-01

    Donor T cells that respond to host alloantigens following allogeneic bone marrow transplantation (BMT) induce graft-versus-host (GVH) responses, but their molecular landscape is not well understood. MicroRNAs (miRNAs) regulate gene (mRNA) expression and fine-tune the molecular responses of T cells. We stimulated naive T cells with either allogeneic or nonspecific stimuli and used argonaute cross-linked immunoprecipitation (CLIP) with subsequent ChIP microarray analyses to profile miR responses and their direct mRNA targets. We identified a unique expression pattern of miRs and mRNAs following the allostimulation of T cells and a high correlation between the expression of the identified miRs and a reduction of their mRNA targets. miRs and mRNAs that were predicted to be differentially regulated in allogeneic T cells compared with nonspecifically stimulated T cells were validated in vitro. These analyses identified wings apart-like homolog (Wapal) and synaptojanin 1 (Synj1) as potential regulators of allogeneic T cell responses. The expression of these molecular targets in vivo was confirmed in MHC-mismatched experimental BMT. Targeted silencing of either Wapal or Synj1 prevented the development of GVH response, confirming a role for these regulators in allogeneic T cell responses. Thus, this genome-wide analysis of miRNA-mRNA interactions identifies previously unrecognized molecular regulators of T cell responses. PMID:24216511

  1. A comparative study of young and mature bovine cortical bone.

    PubMed

    Manilay, Zherrina; Novitskaya, Ekaterina; Sadovnikov, Ernest; McKittrick, Joanna

    2013-02-01

    The mechanical properties and microstructure of young and mature bovine femur bone were investigated by optical microscopy and compression testing in the longitudinal and transverse directions for untreated, deproteinized and demineralized cases. Optical microscopy revealed that mature bone has a more established and less porous microstructure compared to young bone. Mature bone was found to be stronger in both directions for the untreated and deproteinized cases. Mature untreated bone was also found to be stiffer and less tough compared to young bone in both directions. These results are related to the increase in mineralization of mature bone and significant microstructural differences. Young bone was found to be stronger in both directions for the demineralized case, which is attributed to alterations in the collagen network with age.

  2. The effect of stromelysin-1 (MMP-3) on non-collagenous extracellular matrix proteins of demineralized dentin and the adhesive properties of restorative resins.

    PubMed

    Boukpessi, T; Menashi, S; Camoin, L; Tencate, J M; Goldberg, M; Chaussain-Miller, C

    2008-11-01

    Dentin non-collagenous matrix components (NCPs) are structural proteins involved in the formation, the architecture and the mineralization of the extracellular matrix (ECM). We investigated here how recombinant metalloproteinase stromelysin-1, also termed MMP-3, initiates the release of ECM molecules from artificially demineralized human dentin. Analysis of the supernatants by Western blotting reveals that MMP-3 extracts PGs (decorin, biglycan), and also a series of phosphorylated proteins: dentin sialoprotein (DSP), osteopontin (OPN), bone sialoprotein (BSP) and MEPE, but neither dentin matrix protein-1 (DMP1), another member of the SIBLING family, nor osteocalcin (OC), a non-phosphorylated matrix molecule. After treatment of dentin surfaces by MMP-3, scanning electron microscope (SEM) examination of resin replica shows an increased penetration of the resin into the dentin tubules when compared to surfaces only treated by demineralizing solutions. This preclinical investigation suggests that MMP-3 may be used to improve the adhesive properties of restorative materials.

  3. Influence of Photoactivation Source on Restorative Materials and Enamel Demineralization

    PubMed Central

    Popoff, Josiane Marques de Sena; Rodrigues, José Augusto; Aras, Wanessa Maria De Freitas

    2014-01-01

    Abstract Objective: The objective of this study was to evaluate the influence of the photoactivation source on the polymerization depth of restorative materials and its effects on resistance to enamel demineralization. Background data: Argon-ion laser (AL) irradiation itself provides a reduced depth of caries lesions in sound enamel. Methods: Eighteen human teeth were sectioned into 36 blocks and distributed into two groups according to the respective restorative material: resin-modified glass ionomer material (RMGI) (Vitremer-3M ESPE; A3; n=18) and composite resin (CR) (Z350-3M ESPE; n=18). Each group was subdivided into three subgroups and activated by a quartz-tungsten-halogen (QTH) lamp, an AL, or a light-emitting diode (LED) (n=6). Knoop microhardness (KHN) analysis of the materials was evaluated at two different depths: 0 and 1.6 mm from the enamel surface. The blocks were thermocycled and submitted to five demineralization–remineralization cycles at 37°C. The KHN values of the enamel surface (0 mm) were evaluated. The specimens were longitudinally sectioned, and the restorative material was evaluated at a depth of 1.6 mm. Data were evaluated by two way analysis of variance (ANOVA) and Tukey tests (p<0.05). The evaluation of subsuperficial enamel demineralization by KHN analysis was conducted by seven indentations located at 100 μm from the restored cavity. Data were evaluated by three way ANOVA and Tukey tests (p<0.05). Results: Comparing the two restorative materials, the KHN values at the surface (0 mm) were greater for CR, whereas at 1.6 mm, they were greater for RMGI. In addition, there was less development of enamel demineralization around RMGI restorations than CR restorations. Moreover, there were statistically significant differences on subsuperficial enamel demineralization between the two restorative materials and between the three photoactivation methods (p<0.05); RMGI presented the highest KHN values, and QTH and AL presented the

  4. Repair of Segmental Load-Bearing Bone Defect by Autologous Mesenchymal Stem Cells and Plasma-Derived Fibrin Impregnated Ceramic Block Results in Early Recovery of Limb Function

    PubMed Central

    Ng, Min Hwei; Duski, Suryasmi; Tan, Kok Keong; Yusof, Mohd Reusmaazran; Low, Kiat Cheong; Mohamed Rose, Isa; Mohamed, Zahiah; Bin Saim, Aminuddin; Idrus, Ruszymah Bt Hj

    2014-01-01

    Calcium phosphate-based bone substitutes have not been used to repair load-bearing bone defects due to their weak mechanical property. In this study, we reevaluated the functional outcomes of combining ceramic block with osteogenic-induced mesenchymal stem cells and platelet-rich plasma (TEB) to repair critical-sized segmental tibial defect. Comparisons were made with fresh marrow-impregnated ceramic block (MIC) and partially demineralized allogeneic bone block (ALLO). Six New Zealand White female rabbits were used in each study group and three rabbits with no implants were used as negative controls. By Day 90, 4/6 rabbits in TEB group and 2/6 in ALLO and MIC groups resumed normal gait pattern. Union was achieved significantly faster in TEB group with a radiological score of 4.50 ± 0.78 versus ALLO (1.06 ± 0.32), MIC (1.28 ± 0.24), and negative controls (0). Histologically, TEB group scored the highest percentage of new bone (82% ± 5.1%) compared to ALLO (5% ± 2.5%) and MIC (26% ± 5.2%). Biomechanically, TEB-treated tibiae achieved the highest compressive strength (43.50 ± 12.72 MPa) compared to those treated with ALLO (15.15 ± 3.57 MPa) and MIC (23.28 ± 6.14 MPa). In conclusion, TEB can repair critical-sized segmental load-bearing bone defects and restore limb function. PMID:25165699

  5. The Application of Bone Marrow Transplantation to the Treatment of Genetic Diseases

    NASA Astrophysics Data System (ADS)

    Parkman, Robertson

    1986-06-01

    Genetic diseases can be treated by transplantation of either normal allogeneic bone marrow or, potentially, autologous bone marrow into which the normal gene has been inserted in vitro (gene therapy). Histocompatible allogeneic bone marrow transplantation is used for the treatment of genetic diseases whose clinical expression is restricted to lymphoid or hematopoietic cells. The therapeutic role of bone marrow transplantation in the treatment of generalized genetic diseases, especially those affecting the central nervous system, is under investigation. The response of a generalized genetic disease to allogeneic bone marrow transplantation may be predicted by experiments in vitro. Gene therapy can be used only when the gene responsible for the disease has been characterized. Success of gene therapy for a specific genetic disease may be predicted by its clinical response to allogeneic bone marrow transplantation.

  6. Prevention of enamel demineralization adjacent to glass ionomer filling materials.

    PubMed

    Forss, H; Seppä, L

    1990-04-01

    In order to study the release of fluoride and prevention of enamel demineralization by different filling materials, standardized cavities were prepared in 80 extracted human molars. The cavities were filled as follows: 1. Fuji II F; 2. Ketac-Fil; 3. Ketac-Silver; 4. Silar. Twenty molars were used as controls (no filling). Enamel slabs with the fillings were subjected to 9 days of demineralization (30 min daily) and remineralization (artificial saliva, replaced daily). Fluoride release in the saliva was determined on days 1, 3, 5, and 9. Enamel fluoride content adjacent to the cavities was determined initially and after the de-remineralization using the acid etch technique. On day 1, the largest amount of fluoride in the saliva was released by Fuji, but on day 9 the largest amount was released by Ketac-Fil. Ketac-Silver released significantly less fluoride than Fuji and Ketac-Fil. The average initial fluoride content of enamel was 2200 ppm. After the test period, fluoride contents adjusted for biopsy depth were 1822, 1690, 1693, 1337, and 888 ppm in groups 1-5, respectively. The amounts of phosphorus dissolved by the second acid etch were 28.9 (SE 2.6), 30.2 (2.0), 34.4 (2.8), 44.1 (2.7), and 42.2 (2.4) micrograms, respectively. Softening of surface enamel during the test period was clearly reduced in teeth filled with Fuji and Ketac-Fil. The results show that glass ionomer materials release considerable amounts of fluoride and prevent demineralization of the adjacent enamel in vitro. Fuji and Ketac-Fil seem to be more effective than Ketac-Silver.

  7. Multi-Institutional Study of Post-Transplantation Cyclophosphamide As Single-Agent Graft-Versus-Host Disease Prophylaxis After Allogeneic Bone Marrow Transplantation Using Myeloablative Busulfan and Fludarabine Conditioning

    PubMed Central

    Kanakry, Christopher G.; O'Donnell, Paul V.; Furlong, Terry; de Lima, Marcos J.; Wei, Wei; Medeot, Marta; Mielcarek, Marco; Champlin, Richard E.; Jones, Richard J.; Thall, Peter F.; Andersson, Borje S.; Luznik, Leo

    2014-01-01

    Purpose The clinical safety and efficacy of intravenous busulfan and fludarabine (IV Bu/Flu) myeloablative conditioning as well as graft-versus-host disease (GVHD) prophylaxis with high-dose, post-transplantation cyclophosphamide (PTCy) have been demonstrated independently in several single-institutional studies. We hypothesized that combining these two promising approaches in a multi-institutional study of human leukocyte antigen (HLA) -matched bone marrow transplantation would provide low rates of severe acute and chronic GVHD, low toxicity, and effective disease control. Patients and Methods Ninety-two adult patients (median age, 49 years; range, 21 to 65 years) with high-risk hematologic malignancies were enrolled at three centers (clinical trial No. NCT00809276). Forty-five patients received related allografts, and 47 received unrelated allografts. GVHD prophylaxis was solely with PTCy at 50 mg/kg/day on post-transplantation days +3 and +4. Results The cumulative incidences of grades 2 to 4 acute, grades 3 to 4 acute, and chronic GVHD were 51%, 15%, and 14%, respectively. Nonrelapse mortality (NRM) at 100 days and 1 year were 9% and 16%, respectively. With a median follow-up period of 2.2 years, the 2-year disease-free survival (DFS) and overall survival (OS) rates were 62% and 67%, respectively. Donor relatedness did not affect NRM, DFS, or OS. Patients in complete remission (CR) without evidence of minimal residual disease (MRD) had markedly better DFS (80%) and OS (80%) than patients in CR with MRD or with active disease at the time of transplantation (DFS, P = .0005; OS, P = .019). Conclusion This multi-institutional study demonstrates that PTCy can be safely and effectively combined with IV Bu/Flu myeloablative conditioning and confirms PTCy's efficacy as single-agent, short-course GVHD prophylaxis for both acute and chronic GVHD after bone marrow transplantation from HLA-matched donors. PMID:25267759

  8. Effect of electrical current on the healing of mandibular freeze-dried bone allografts in dogs

    SciTech Connect

    Branham, G.B.; Triplett, R.G.; Yeandle, S.; Vieras, F.

    1985-06-01

    Low levels of electrical current have been shown to affect the process of osseous repair. This study experimentally evaluated the effect of electrical stimulation on the healing of freeze-dried mandibular allogeneic bone grafts in dogs. Healing of the grafts was monitored by sequential submento-occlusal radiographs and radionuclide bone imaging at two, four, six, and eight weeks after grafting. Results indicated no significant difference in the osseous repair of stimulated and nonstimulated freeze-dried allogeneic bone grafts.

  9. The inhibition of demineralization of human enamel after fluoride varnish application as a function of the fluoride content. An in vitro study under constant composition demineralizing conditions.

    PubMed

    de Bruyn, H; Buskes, J A; Arends, J

    1986-06-01

    The inhibiting effect of a 24 hours application of a fluoridated varnish with various fluoride contents on demineralization of human sound enamel was evaluated in vitro. The varnishes used had the same polyurethane base (Fluor Protector) and contained 0.7; 0.1; 0.05 and 0 wt% fluoride, resp. A constant composition technique was used to demineralize varnished and non-varnished specimens at a pH of 5 for periods upto 2 weeks. Microhardness measurements were carried out after several time intervals to follow mineral loss in time longitudinally. At the end of each experimental run microradiography was carried out to investigate 1) lesion type, 2) lesion depth and 3) mineral loss. It is shown in this study that the fluoride releasing varnishes applied on the enamel for 24 hours can inhibit demineralization completely. No demineralization inhibition with the 0% fluoride varnish application was observed.

  10. Assessment of cervical demineralization induced by Streptococcus mutans using swept-source optical coherence tomography.

    PubMed

    Tezuka, Hiroki; Shimada, Yasushi; Matin, Khairul; Ikeda, Masaomi; Sadr, Alireza; Sumi, Yasunori; Tagami, Junji

    2016-01-01

    Exposed root surfaces due to gingival recession are subject to biofilm stagnation that can result in caries formation. Cervical enamel and dentin demineralization induced by a cariogenic biofilm was evaluated using swept-source optical coherence tomography (SS-OCT). The cementoenamel junction (CEJ) sections of extracted human teeth were subjected to demineralization for 1, 2, or 3 weeks. A suspension of Streptococcus mutans was applied to form a cariogenic biofilm using an oral biofilm reactor. After incubation, demineralization was observed by SS-OCT. For the analysis of SS-OCT signal, the value of the area under the curve (AUC) of the signal profile was measured. Statistical analyses were performed with 95% level of confidence. Cervical demineralization was displayed as a bright zone in SS-OCT. The demineralization depth of dentin was significantly deeper than that of enamel ([Formula: see text]). Enamel near the CEJ demonstrated a significant increase of AUC over the other enamel region after the demineralization. The gaps along the dentinoenamel junction were additionally observed in SS-OCT. SS-OCT was capable of monitoring the cervical demineralization induced by a cariogenic biofilm and is considered to be a promising modality for the diagnosis of cervical demineralization. PMID:27014718

  11. Porous poly(propylene fumarate) foam coating of orthotopic cortical bone grafts for improved osteoconduction.

    PubMed

    Lewandrowski, Kai-Uwe; Bondre, Shrikar; Hile, David D; Thompson, Benjamin M J; Wise, Donald L; Tomford, William W; Trantolo, Debra J

    2002-12-01

    A porous biodegradable scaffold coating for perforated and demineralized cortical bone allografts could maintain immediate structural recovery and subsequently allow normal healing and remodeling by promoting bony ingrowth and avoiding accelerated graft resorption. This new type of osteoconductive surface modification should improve allograft incorporation by promoting new bone growth throughout the biodegradable scaffold, hence encasing the graft with the recipient's own bone. We investigated the feasibility of augmenting orthotopically transplanted cortical bone grafts with osteoconductive biodegradable polymeric scaffold coatings. Five types of bone grafts were prepared: type I, untreated fresh-frozen cortical bone grafts (negative control); type II, perforated and partially demineralized cortical bone grafts without additional coating (positive control); type III, perforated and partially demineralized cortical bone coated with a low-porosity poly(propylene fumarate) (PPF) foam; type IV, perforated and partially demineralized cortical bone coated with a medium-porosity PPF foam; and type V, perforated and partially demineralized cortical bone coated with a high-porosity PPF foam. Grafts were implanted into the rat tibial diaphysis. Fixation was achieved with an intramedullary threaded K-wire. Two sets of animals were operated on. Animals were killed in groups of eight with one set being killed 12 weeks, and the other 16 weeks, postoperatively. Radiographic, histologic, and histomorphometric analyses of grafts showed that the amount of new bone forming around the foam-coated grafts was significantly higher than that in the type I control group (uncoated) or that in type II group (perforated and partially demineralized cortical bone grafts). Although all foam formulations appeared initially equally osteoconductive, histologic evaluation of medium-porosity PPF foam-based coatings appeared to result in a sustained response 16 weeks postoperatively. Significant

  12. Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits.

    PubMed

    Chiang, En-Rung; Ma, Hsiao-Li; Wang, Jung-Pan; Liu, Chien-Lin; Chen, Tain-Hsiung; Hung, Shih-Chieh

    2016-01-01

    Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.

  13. Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits

    PubMed Central

    Chiang, En-Rung; Ma, Hsiao-Li; Wang, Jung-Pan; Liu, Chien-Lin; Chen, Tain-Hsiung; Hung, Shih-Chieh

    2016-01-01

    Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo. PMID:26915044

  14. Preparation and characterization of activated carbon from demineralized tyre char

    NASA Astrophysics Data System (ADS)

    Manocha, S.; Prasad, Guddu R.; Joshi, Parth.; Zala, Ranjitsingh S.; Gokhale, Siddharth S.; Manocha, L. M.

    2013-06-01

    Activated carbon is the most adsorbing material for industrial waste water treatment. For wider applications, the main consideration is to manufacture activated carbon from low cost precursors, which are easily available and cost effective. One such source is scrap tyres. Recently much effort has been devoted to the thermal degradation of tyres into gaseous and liquid hydrocarbons and solid char residue, all of which have the potential to be processed into valuable products. As for solid residue, char can be used either as low-grade reinforcing filler or as activated carbon. The product recovered by a typical pyrolysis of tyres are usually, 33-38 wt% pyrolytic char, 38-55 wt% oil and 10-30 wt% solid fractions. In the present work activated carbon was prepared from pyrolyzed tyre char (PC). Demineralization involves the dissolution of metal into acids i.e. HCl, HNO3 and H2SO4 and in base i.e. NaOH. Different concentration of acid and base were used. Sodium hydroxide showed maximum amount of metal oxide removal. Further the concentration of sodium hydroxide was varied from 1N to 6N. As the concentration of acid are increased demineralization increases. 6N Sodium hydroxide is found to be more effective demineralising agent of tyre char.

  15. Analysis of donor NK and T cells infused in patients undergoing MHC-matched allogeneic hematopoietic transplantation.

    PubMed

    Pascal, V; Brunet, C; Pradel, V; Thirion, X; Andre, P; Faucher, C; Sampol, J; Dignat-George, F; Blaise, D; Vivier, E; Chabannon, C

    2002-11-01

    We retrospectively analyzed the percentages and absolute numbers of T cells, natural killer (NK) cells and NK cell subsets in cryopreserved samples of either bone marrow or blood non-T cell-depleted allogeneic MHC-matched hematopoietic grafts. Using flow cytometry, we found higher numbers of NK cells in aphereses than in bone marrow collections. We further investigated the distribution of NK cell subsets, defined by the cell surface expression of MHC class I-specific receptors, in these allogeneic grafts. The distribution of NK cell subsets from the two different origins were similar, with the exception of the CD158a/h(+) NK cell subset, whose size appeared to be smaller in bone marrow. The search for relations between the numbers of infused cells and post-transplantation events demonstrated that increasing numbers of infused T cells but not NK cells are related with decreased overall survival. Our study highlights the toxicity of infused T cells but not NK cells in allogeneic MHC-matched hematopoietic grafts. These data pave the way for further trials to investigate the effect of NK cell infusion in MHC-matched allogeneic transplantation, and in particular whether ex vivo NK cell expansion and activation may enhance the anti-tumoral effect of the procedure and decrease its morbidity.

  16. IL-22 promoted CD3+ T cell infiltration by IL-22R induced STAT3 phosphorylation in murine acute graft versus host disease target organs after allogeneic bone marrow transplantation.

    PubMed

    Zhao, Kai; Ruan, Suhong; Tian, Yu; Zhao, Dongmei; Chen, Chong; Pan, Bin; Yan, Zhiling; Yin, Lingling; Zhu, Shengyun; Xu, Kailin

    2016-10-01

    Graft versus host disease (GVHD) is a life threatening complication of bone marrow stem cell transplantation, in which considerable numbers of proinflammatory cytokines secreted by allo-reactive donor T cells are involved. We and other previous studies have found that interleukin-22 (IL-22) was able to aggravate the target organs damage of GVHD. However, the mechanism and the signal pathway of IL-22 in murine acute GVHD was not clear. Here, we observed that compared with GVHD group, more serious pathological damage and more CD3(+) T cells infiltrated in GVHD target organs were detected in the mice injected with IL-22. Meanwhile, transcription factor T-bet, RORγt and AhR respectively associated with Th1, Th17 and Th22 cells changed in varying degrees in different GVHD target organs. Furthermore, the increased expression of IL-22R and its downstream protein P-STAT3 were detected in GVHD mice with IL-22 treated. These results suggested that the pathological role of IL-22 in GVHD target organs contribute to exogenous injected IL-22 as well as secreted IL-22 from the infiltrated allo-reactive effector T cells. In addition, the IL-22R-STAT3 pathway may play important role in GVHD tissue injury and target this way may yield new approaches for reduction of GVHD. PMID:27551984

  17. Are allogenic or xenogenic screws and plates a reasonable alternative to alloplastic material for osteosynthesis--a histomorphological analysis in a dynamic system.

    PubMed

    Jacobsen, C; Obwegeser, J A

    2010-12-01

    Despite invention of titanium and resorbable screws and plates, still, one of the main challenges in bone fixation is the search for an ideal osteosynthetic material. Biomechanical properties, biocompatibility, and also cost effectiveness and clinical practicability are factors for the selection of a particular material. A promising alternative seems to be screws and plates made of bone. Recently, xenogenic bone pins and screws have been invented for use in joint surgery. In this study, screws made of allogenic sheep and xenogenic human bone were analyzed in a vital and dynamic sheep-model and compared to conventional titanium screws over a standard period of bone healing of 56 days with a constant applied extrusion force. Biomechanical analysis and histomorphological evaluation were performed. After 56 days of insertion xenogenic screws made of human bone showed significantly larger distance of extrusion of on average 173.8 μm compared to allogenic screws made of sheep bone of on average 27.8 and 29.95 μm of the titanium control group. Severe resorption processes with connective tissue interposition were found in the histomorphological analysis of the xenogenic screws in contrast to new bone formation and centripetal vascularization of the allogenic bone screw, as well as in processes of incorporation of the titanium control group. The study showed allogenic cortical bone screws as a substantial alternative to titanium screws with good biomechanical properties. In contrast to other reports a different result was shown for the xenogenic bone screws. They showed insufficient holding strength with confirmative histomorphological signs of degradation and insufficient osseointegration. Before common clinical use of xenogenic osteosynthetic material, further evaluation should be performed. PMID:20813368

  18. Effects of Ion-Releasing Tooth-Coating Material on Demineralization of Bovine Tooth Enamel

    PubMed Central

    Kawasaki, Koji; Kambara, Masaki

    2014-01-01

    We compared the effect of a novel ion-releasing tooth-coating material that contained S-PRG (surface-reaction type prereacted glass-ionomer) filler to that of non-S-PRG filler and nail varnish on the demineralization of bovine enamel subsurface lesions. The demineralization process of bovine enamel was examined using quantitative light-induced fluorescence (QLF) and electron probe microanalyzer (EPMA) measurement. Ion concentrations in demineralizing solution were measured using inductively coupled plasma atomic (ICP) emission spectrometry and an ion electrode. The nail varnish group and the non-S-PRG filler group showed linear demineralization. Although the nail varnish group and the non-S-PRG filler group showed linear demineralization, the S-PRG filler group did not. Further, plane-scanning by EPMA analysis in the S-PRG filler group showed no changes in Ca ion distribution, and F ions showed peak levels on the surface of enamel specimens. Most ions in the demineralizing solution were present at higher concentrations in the S-PRG filler group than in the other two groups. In conclusion, only the S-PRG filler-containing tooth-coating material released ions and inhibited demineralization around the coating. PMID:24578706

  19. Comparative reduction of enamel demineralization by calcium and phosphate in vitro.

    PubMed

    Tanaka, M; Kadoma, Y

    2000-01-01

    In theory, calcium and phosphate in the plaque fluid exert a large influence on the demineralization of enamel surface. In order to know the effect of increasing the concentration of either of these factors, the following in vitro experiment was conducted. Three thin sections, about 150 Im thick, were cut out from each of 13 human premolars. All surfaces of the sections, except for the original enamel surface, were coated with nail varnish. These sections were immersed into one of two sets of demineralizing solutions for 1 week at 25 degrees C. Each set, the 'calcium set' and the 'phosphate set', contained three solutions. The composition of these solutions differed mainly in calcium or phosphate concentrations. After 1 week, the degree of demineralization was determined by image analysis of contact microradiograms from each section. The subsurface demineralization in enamel was reduced by 95% by increasing the calcium concentration of the demineralizing solution from 7 to 21 mmol/l. A similar reduction (87%) was observed by increasing the phosphate concentration. However, the amount of phosphate needed was approximately 20 times more than that of calcium. The larger inhibitory effect that calcium has on enamel demineralization was related to the larger effect it has on the degree of saturation of the solution. Even though no statistically significant difference was found between the effect of calcium and phosphate on the demineralization of enamel (when the solutions had the same degree of saturation), the difference in the standard deviation of demineralization suggests the existence of some other factors which have an influence on the demineralization reaction. PMID:10867423

  20. Near-infrared imaging of demineralization under sealants

    NASA Astrophysics Data System (ADS)

    Tom, Henry; Simon, Jacob C.; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

    2014-07-01

    Previous studies have shown that near-infrared (NIR) reflectance and transillumination imaging can be used to acquire high contrast images of early caries lesions and composite restorative materials. The aim of the study was to determine the optimum NIR wavelengths for imaging demineralized areas under dental sealants. Fifteen natural human premolars and molars with occlusal lesions were used in this in vitro study. Images before and after application of sealants were acquired using NIR reflectance and NIR transillumination at wavelengths of 1300, 1460, and 1500 to 1700 nm. Images were also acquired using polarization sensitive optical coherence tomography (OCT) for comparison. The highest contrast for NIR reflectance was at 1460 nm and 1500 to 1700 nm. These NIR wavelengths are coincident with higher water absorption. The clear Delton sealant investigated was not visible in either copolarization or cross-polarization OCT images. The wavelength region between 1500 and 1700 nm yielded the highest contrast of lesions under sealants for NIR reflectance measurements.

  1. Penetration of varnishes into demineralized root dentine in vitro.

    PubMed

    Arends, J; Duschner, H; Ruben, J L

    1997-01-01

    In this paper the penetration of three different varnishes employed in caries prevention (Duraphat, Fluor Protector and Cervitec) into demineralized dentine is quantified using confocal laser scanning microscopy. The results show that the varnish penetration into lesions about 85 microns in depth if for Cervitec about 35 microns and considerably less for Duraphat and Fluor Protector. The penetration is into the dentinal tubules and is influenced by dentinal tubule direction. The drying procedure--pretreatment of the dentine--influences the penetration, though sizeably only for Cervitec applications. This paper shows that varnish penetration into the tissue and presumably 'sealing' tubules completely or partly is valuable with respect to root caries prevention and hypersensitivity. PMID:9165191

  2. Holmium:YAG laser: effects on dentin demineralization

    NASA Astrophysics Data System (ADS)

    Holt, Raleigh A.; Nordquist, Robert E.

    1995-05-01

    The Holmium:YAG laser at 2.12 microns wavelength was used to compare the changes in resistance to demineralization of the dentinal root surfaces of human extracted teeth in vitro. Three protocols were used: Group #1, and application of nonfilled resin/NaF (4%) solution followed by exposure with the Holmium:YAG laser beam; Group #2, an application of an aqueous solution of NaF (4%) only; and Group #3, irradiation with the laser beam only. The teeth were exposed on the root surfaces with untreated control and experimental sites on opposite sides of the teeth. A 3 mm spot size covered an area of 3 X 5 mm with 0.450 (+/- .05) joules at a fluence of 2.66 - 3.3 J/cm2. All teeth were decalcified in a 10% Formic acid solution for a timed period. Samples were prepared for staining by sectioning the teeth at the dentoenamel junction and 3 mm apically to produce a cross-section of each tooth root surface. Each sample was placed in toluidine blue dye to observe the depth of dye penetration into the dentin of treated and control sites. Toluidine blue dye showed a consistent greater depth of dye penetration into the dentinal areas of the untreated control sites versus the resin/NaF-lased group. The topical fluoride only group did not appear different than the untreated control sites of the teeth. The lased only group showed areas of dye penetration similar to the untreated control sides with other areas of little or no dye penetration. The finding that HO:YAG laser energy/chemical agent produced increased resistance to demineralization of dentinal surfaces in vitro suggested potential clinical applications of this combined modality.

  3. In vitro demineralization of enamel by orange juice, apple juice, Pepsi Cola and Diet Pepsi Cola.

    PubMed

    Grobler, S R; Senekal, P J; Laubscher, J A

    1990-12-01

    Enamel demineralization was studied over periods related to normal use of an orange juice, an apple juice, Pepsi Cola and Diet Pepsi Cola. Rectangular blocks of intact human enamel (3 mm x 3 mm) were cut from teeth, coated with nail varnish except for the enamel surface and exposed to the drinks for 2, 4, 5, 6 or 40 minutes. The amount of calcium released from the enamel into solution was determined with the use of an atomic absorption spectrophotometer. The results showed the following degree of enamel demineralization: Pepsi Cola = orange juice greater than apple juice greater than Diet Pepsi Cola. The results suggest that diet colas are less demineralizing than other acid drinks, and complementary plaque studies indicate that they are also less cariogenic. The study emphasized the importance of acid-type, buffer capacity, pH and the presence of other components on the degree of enamel demineralization.

  4. Protein loss of bovine dental enamel during in-vitro subsurface demineralization.

    PubMed

    van der Linden, A H; Booij, M; ten Bosch, J J; Arends, J

    1985-01-01

    A chemical system based on the dialysis principle was used to study protein loss of dental enamel during demineralization with an acetic-acid buffer solution containing calcium and phosphate, in which the fluoride-ion activity was kept constant. This resulted in a subsurface lesion, with a depth of about 130 microns. After demineralization, protein material was isolated from the demineralization solution. u.v. Spectra of the protein showed strong absorbance between 240 and 300 nm. Amino-acid composition showed high glycine, glutamic acid, proline, serine and aspartic acid contents. After 10 days demineralization, the total protein loss was 3 micrograms cm-2; the mineral loss was 16 mg cm-2. Compared with the total enamel-protein content (0.06-0.09 wt per cent) protein loss (0.018 per cent of total lost material) was not proportional to the mineral loss, when a subsurface lesion was formed.

  5. DEMINERALIZER BUILDING, TRA608. INSTALLATION OF SAMPLING AND OTHER INSTRUMENTS COMPLETES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DEMINERALIZER BUILDING, TRA-608. INSTALLATION OF SAMPLING AND OTHER INSTRUMENTS COMPLETES DEMINERALIZER UNITS ALONG NORTH WALL. CAMERA FACES EAST. CARD IN LOWER RIGHT WAS INSERTED BY INL PHOTOGRAPHER TO COVER AN OBSOLETE SECURITY RESTRICTION PRINTED ON THE ORIGINAL NEGATIVE. INL NEGATIVE NO. 3996A. Unknown Photographer, 12/28/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  6. DEMINERALIZER BUILDING,TRA608. CAMERA FACES EAST ALONG SOUTH WALL. INSTRUMENT PANEL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DEMINERALIZER BUILDING,TRA-608. CAMERA FACES EAST ALONG SOUTH WALL. INSTRUMENT PANEL BOARD IS IN RIGHT HALF OF VIEW, WITH FOUR PUMPS BEYOND. SMALLER PUMPS FILL DEMINERALIZED WATER TANK ON SOUTH SIDE OF BUILDING. CARD IN LOWER RIGHT WAS INSERTED BY INL PHOTOGRAPHER TO COVER AN OBSOLETE SECURITY RESTRICTION PRINTED ON ORIGINAL NEGATIVE. INL NEGATIVE NO. 3997A. Unknown Photographer, 12/28/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  7. [Osteoplastic effectiveness of mineralized bone matrix].

    PubMed

    2013-01-01

    In the experiment conducted on 50 Wistar rats, the peculiarities of the reparative osteogenesis were studied using scanning electron microscopy, x-ray electron-probe microanalysis and histological techniques. Granulated mineralized bone matrix (MBM) obtained without thermal and demineralizing treatment, was implanted into the tibial defect. MBM was found to possess marked osteoinductive and osteoconductive properties. It induced a prolonged activation of reparative osteogenesis after the implantation, as well as deep bone tissue ingrowth into the implant, acceleration of organotypic remodeling of regenerated bone, intense angiogenesis and early restoration of the damaged

  8. [Osteoplastic effectiveness of mineralized bone matrix].

    PubMed

    2013-01-01

    In the experiment conducted on 50 Wistar rats, the peculiarities of the reparative osteogenesis were studied using scanning electron microscopy, x-ray electron-probe microanalysis and histological techniques. Granulated mineralized bone matrix (MBM) obtained without thermal and demineralizing treatment, was implanted into the tibial defect. MBM was found to possess marked osteoinductive and osteoconductive properties. It induced a prolonged activation of reparative osteogenesis after the implantation, as well as deep bone tissue ingrowth into the implant, acceleration of organotypic remodeling of regenerated bone, intense angiogenesis and early restoration of the damaged PMID:23805618

  9. Bone marrow processing for transplantation using Cobe Spectra cell separator.

    PubMed

    Veljković, Dobrila; Nonković, Olivera Šerbić; Radonjić, Zorica; Kuzmanović, Miloš; Zečević, Zeljko

    2013-06-01

    Concentration of bone marrow aspirates is an important prerequisite prior to infusion of ABO incompatible allogeneic marrow and prior to cryopreservation and storage of autologous marrow. In this paper we present our experience in processing 15 harvested bone marrow for ABO incompatible allogeneic and autologous bone marrow (BM) transplantation using Cobe Spectra® cell separator. BM processing resulted in the median recovery of 91.5% CD34+ cells, erythrocyte depletion of 91% and volume reduction of 81%. BM processing using cell separator is safe and effective technique providing high rate of erythrocyte depletion and volume reduction, and acceptable recovery of the CD34+ cells.

  10. Electromechanical Properties of Bone Tissue.

    NASA Astrophysics Data System (ADS)

    Regimbal, Raymond L.

    Discrepancies between calculated and empirical properties of bone are thought to be due to a general lack of consideration for the extent and manner(s) with which bone components interact at the molecular level. For a bone component in physiological fluid or whenever two phases are in contact, there is a region between the bulk phases called the electrical double layer which is marked by a separation of electric charges. For the purpose of studying electrical double layer interactions, the method of particle microelectrophoresis was used to characterize bone and its major constituents on the basis of the net charge they bear when suspended in ionic media of physiological relevance. With the data presented as pH versus zeta (zeta ) potential, the figures reveal an isoelectric point (IEP) for bone mineral near pH 8.6, whereas intact and EDTA demineralized bone tissue both exhibit IEPs near pH 5.1. While these data demonstrate the potential for a significant degree of coulombic interaction between the bone mineral and organic constituent double layers, it was also observed that use of inorganic phosphate buffers, as a specific marker for bone mineral, resulted in (1) an immediate reversal, from positive to negative, of the bone mineral zeta potential (2) rendered the zeta potential of intact bone more negative in a manner linearly dependent on both time and temperature and (3) had no affect on demineralized bone (P < 0.01). In agreement with that shown in model protein-hydroxyapatite systems, it is suggested here that inorganic phosphate ions in solution compete with organic acid groups (e.g. carboxyl and phosphate of collagen, sialoprotein, ...) for positively charged sites on the bone mineral surface and effectively uncouple the bone mineral and organic phase double layers. Mechanically, this uncoupling is manifested as a loss of tissue rigidity when monitoring the midspan deflection of bone beams subject to constant load for a 3 day period. While it is thus

  11. Bone disease in primary hypercalciuria

    PubMed Central

    Sella, Stefania; Cattelan, Catia; Realdi, Giuseppe; Giannini, Sandro

    2008-01-01

    Primary Hypercalciuria (PH) is very often accompanied with some degrees of bone demineralization. The most frequent clinical condition in which this association has been observed is calcium nephrolithiasis. In patients affected by this disorder bone density is very frequently low and increased susceptibility to fragility fractures is reported. The very poor definition of this bone disease from a histomorphometric point of view is a crucial aspect. At present, the most common finding seems to be a low bone turnover condition. Many factors are involved in the complex relationships between bone loss and PH. Since bone loss was mainly reported in patients with fasting hypercalciuria, a primary alteration in bone metabolism was proposed as a cause of both hypercalciuria and bone demineralization. This hypothesis was strengthened by the observation that some bone resorbing-cytokines, such as IL-1, IL-6, and TNF-α are high in hypercalciuric patients. The effect of an excessive response to the acid load induced by dietary protein intake seems an additional factor explaining a primitive alteration of bone. The intestine plays a major role in the clinical course of bone disease in PH. Patients with absorptive hypercalciuria less frequently show bone disease and a reduction in dietary calcium greatly increases the probability of bone loss in PH subjects. It has recently been reported that greater bone loss is associated with a larger increase in intestinal calcium absorption in PH patients. Considering the absence of PTH alterations, it was proposed that this is not a compensatory phenomenon, but probably the marker of disturbed cell calcium transport, involving both intestinal and bone tissues. While renal hypercalciuria is rather uncommon, the kidney still seems to play a role in the pathogenesis of bone loss of PH patients, possibly via the effect of mild to moderate urinary phosphate loss with secondary hypophosphatemia. In conclusion, bone loss is very common in PH

  12. Nondestructive Assessment of Early Tooth Demineralization Using Cross-Polarization Optical Coherence Tomography.

    PubMed

    Kang, Hobin; Jiao, Jian J; Lee, Chulsung; Le, Michael H; Darling, Cynthia L; Fried, Daniel

    2010-07-01

    New methods are needed for the nondestructive measurement of tooth demineralization and remineralization to monitor the progression of incipient caries lesions (tooth decay) for effective nonsurgical intervention and to evaluate the performance of anticaries treatments such as chemical treatments or laser irradiation. Studies have shown that optical coherence tomography (OCT) has great potential to fulfill this role since it can be used to measure the depth and severity of early lesions with an axial resolution exceeding 10 µm, it is easy to apply in vivo and it can be used to image the convoluted topography of tooth occlusal surfaces. In this paper, a review of the use of polarization-sensitive-OCT for the measurement of tooth demineralization is provided along with some recent results regarding improved methods for the detection of caries lesions in the earliest stages of development. Automated methods of analysis were used to measure the depth and severity of demineralized bovine enamel produced using simulated caries models that emulate demineralization in the mouth. Significant differences in the depth and integrated reflectivity from the lesions were detected after only a few hours of demineralization. These results demonstrate that cross-polarization-OCT is ideally suited for the nondestructive assessment of early demineralization.

  13. Nondestructive Assessment of Early Tooth Demineralization Using Cross-Polarization Optical Coherence Tomography

    PubMed Central

    Kang, Hobin; Jiao, Jian J.; Lee, Chulsung; Le, Michael H.; Darling, Cynthia L.; Fried, Daniel

    2011-01-01

    New methods are needed for the nondestructive measurement of tooth demineralization and remineralization to monitor the progression of incipient caries lesions (tooth decay) for effective nonsurgical intervention and to evaluate the performance of anticaries treatments such as chemical treatments or laser irradiation. Studies have shown that optical coherence tomography (OCT) has great potential to fulfill this role since it can be used to measure the depth and severity of early lesions with an axial resolution exceeding 10 µm, it is easy to apply in vivo and it can be used to image the convoluted topography of tooth occlusal surfaces. In this paper, a review of the use of polarization-sensitive-OCT for the measurement of tooth demineralization is provided along with some recent results regarding improved methods for the detection of caries lesions in the earliest stages of development. Automated methods of analysis were used to measure the depth and severity of demineralized bovine enamel produced using simulated caries models that emulate demineralization in the mouth. Significant differences in the depth and integrated reflectivity from the lesions were detected after only a few hours of demineralization. These results demonstrate that cross-polarization-OCT is ideally suited for the nondestructive assessment of early demineralization. PMID:21660217

  14. Allogeneic Transplantation of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets in Canine Critical-Size Supra-Alveolar Periodontal Defect Model.

    PubMed

    Tsumanuma, Yuka; Iwata, Takanori; Kinoshita, Atsuhiro; Washio, Kaoru; Yoshida, Toshiyuki; Yamada, Azusa; Takagi, Ryo; Yamato, Masayuki; Okano, Teruo; Izumi, Yuichi

    2016-01-01

    Periodontitis is a chronic inflammatory disease that induces the destruction of tooth-supporting tissues, followed by tooth loss. Although several approaches have been applied to periodontal regeneration, complete periodontal regeneration has not been accomplished. Tissue engineering using a combination of cells and scaffolds is considered to be a viable alternative strategy. We have shown that autologous transplantation of periodontal ligament-derived multipotent mesenchymal stromal cell (PDL-MSC) sheets regenerates periodontal tissue in canine models. However, the indications for autologous cell transplantation in clinical situations are limited. Therefore, this study evaluated the safety and efficacy of allogeneic transplantation of PDL-MSC sheets using a canine horizontal periodontal defect model. Canine PDL-MSCs were labeled with enhanced green fluorescent protein (EGFP) and were cultured on temperature-responsive dishes. Three-layered cell sheets were transplanted around denuded root surfaces either autologously or allogeneically. A mixture of β-tricalcium phosphate and collagen gel was placed on the bone defects. Eight weeks after transplantation, dogs were euthanized and subjected to microcomputed tomography and histological analyses. RNA and DNA were extracted from the paraffin sections to verify the presence of EGFP at the transplantation site. Inflammatory markers from peripheral blood sera were quantified using an enzyme-linked immunosorbent assay. Periodontal regeneration was observed in both the autologous and the allogeneic transplantation groups. The allogeneic transplantation group showed particularly significant regeneration of newly formed cementum, which is critical for the periodontal regeneration. Serum levels of inflammatory markers from peripheral blood sera showed little difference between the autologous and allogeneic groups. EGFP amplicons were detectable in the paraffin sections of the allogeneic group. These results suggest that

  15. Allogeneic Transplantation of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets in Canine Critical-Size Supra-Alveolar Periodontal Defect Model

    PubMed Central

    Tsumanuma, Yuka; Iwata, Takanori; Kinoshita, Atsuhiro; Washio, Kaoru; Yoshida, Toshiyuki; Yamada, Azusa; Takagi, Ryo; Yamato, Masayuki; Okano, Teruo; Izumi, Yuichi

    2016-01-01

    Abstract Periodontitis is a chronic inflammatory disease that induces the destruction of tooth-supporting tissues, followed by tooth loss. Although several approaches have been applied to periodontal regeneration, complete periodontal regeneration has not been accomplished. Tissue engineering using a combination of cells and scaffolds is considered to be a viable alternative strategy. We have shown that autologous transplantation of periodontal ligament-derived multipotent mesenchymal stromal cell (PDL-MSC) sheets regenerates periodontal tissue in canine models. However, the indications for autologous cell transplantation in clinical situations are limited. Therefore, this study evaluated the safety and efficacy of allogeneic transplantation of PDL-MSC sheets using a canine horizontal periodontal defect model. Canine PDL-MSCs were labeled with enhanced green fluorescent protein (EGFP) and were cultured on temperature-responsive dishes. Three-layered cell sheets were transplanted around denuded root surfaces either autologously or allogeneically. A mixture of β-tricalcium phosphate and collagen gel was placed on the bone defects. Eight weeks after transplantation, dogs were euthanized and subjected to microcomputed tomography and histological analyses. RNA and DNA were extracted from the paraffin sections to verify the presence of EGFP at the transplantation site. Inflammatory markers from peripheral blood sera were quantified using an enzyme-linked immunosorbent assay. Periodontal regeneration was observed in both the autologous and the allogeneic transplantation groups. The allogeneic transplantation group showed particularly significant regeneration of newly formed cementum, which is critical for the periodontal regeneration. Serum levels of inflammatory markers from peripheral blood sera showed little difference between the autologous and allogeneic groups. EGFP amplicons were detectable in the paraffin sections of the allogeneic group. These results suggest

  16. Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies

    ClinicalTrials.gov

    2009-10-14

    Immunologic Deficiency Syndromes; Chediak-Higashi Syndrome; Common Variable Immunodeficiency; Graft Versus Host Disease; X-Linked Lymphoproliferative Syndrome; Familial Erythrophagocytic Lymphohistiocytosis; Hemophagocytic Lymphohistiocytosis; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Hyper IgM Syndrome; Severe Combined Immunodeficiency; Leukocyte Adhesion Deficiency Syndrome; Virus-Associated Hemophagocytic Syndrome

  17. Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders

    ClinicalTrials.gov

    2016-01-21

    Mucopolysaccharidosis; Hurler Syndrome; Hunter Syndrome; Maroteaux-Lamy Syndrome; Sly Syndrome; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Adrenoleukodystrophy (ALD); Krabbe Disease; Metachromatic Leukodystrophy (MLD); Sphingolipidoses; Peroxisomal Disorders

  18. Molecular spectroscopic identification of the water compartments in bone.

    PubMed

    Unal, Mustafa; Yang, Shan; Akkus, Ozan

    2014-10-01

    Matrix bound water is a correlate of bone's fracture resistance and assessment of bound water is emerging as a novel measure of bone's mechanical integrity. Raman spectroscopy is one of the few nondestructive modalities to assess the hydration status in bone; however, it has not been used to study the OH-band in bone. A sequential dehydration protocol was developed to replace unbound (heat drying) and bound (ethanol or deuterium) water in bone. Raman spectra were collected serially to track the OH-band during dehydration. Spectra of synthetic hydroxyapatite, demineralized bone and bulk water were collected to identify mineral and collagen contributions to the OH-band. Band assignments were supported by computational simulations of the molecular vibrations of Gly-Pro-Hyp amino acid sequence. Experimentally and theoretically obtained spectra were interpreted for band-assignments. Water loss was measured gravimetrically and correlated to Raman intensities. Four peaks were identified to be sensitive to dehydration: 3220cm(-1) (water), 3325cm(-1) (NH and water), 3453cm(-1) (hydroxyproline and water), and 3584cm(-1) (mineral and water). These peaks were differentially sensitive to deuterium treatment such that some water peaks were replaced with deuterium oxide faster than the rest. Specifically, the peaks at 3325 and 3584cm(-1) were more tightly bound to the matrix than the remaining bands. Comparison of dehydration in mineralized and demineralized bone revealed a volume of water that may be locked in the matrix by mineral crystals. The OH-range of bone was dominated by collagen and the water since the spectral profile of dehydrated demineralized bone was similar to that of the mineralized bone. Furthermore, water associates to bone mainly by collagen as findings of experimentally and theoretically spectra. The current work is among the first thorough analysis of the Raman OH stretch band in bone and such spectral information may be used to understand the involvement of

  19. Near-IR imaging of demineralization under sealants

    PubMed Central

    Tom, Henry; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

    2014-01-01

    Previous studies have shown that near-IR reflectance and transillumination imaging can be used to acquire high contrast images of early caries lesions and composite restorative materials. The aim of the study was to determine the optimum near-IR wavelengths for imaging demineralized areas under dental sealants. Fifteen natural human premolars and molars with occlusal lesions were used in this in vitro study. Images before and after application of sealants were acquired using near-IR reflectance and near-IR transillumination at wavelengths of 1300 nm, 1460 nm, and 1500 – 1700 nm. Images were also acquired using polarization sensitive optical coherence tomography for comparison. The highest contrast for near-IR reflectance was at 1460 nm and 1500 – 1700 nm. These near-IR wavelengths are coincident with higher water absorption. The clear Delton sealant investigated was not visible in either co-polarization or cross-polarization OCT images. The wavelength region between 1500-1700-nm yielded the highest contrast of lesions under sealants for near-IR reflectance measurements. PMID:24817807

  20. Near-IR imaging of demineralization under sealants

    NASA Astrophysics Data System (ADS)

    Tom, Henry; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

    2014-02-01

    Previous studies have shown that near-IR reflectance and transillumination imaging can be used to acquire high contrast images of early caries lesions and composite restorative materials. The aim of the study was to determine the optimum near-IR wavelengths for imaging demineralized areas under dental sealants. Fifteen natural human premolars and molars with occlusal lesions were used in this in vitro study. Images before and after application of sealants were acquired using near-IR reflectance and near-IR transillumination at wavelengths of 1300 nm, 1460 nm, and 1500 - 1700 nm. Images were also acquired using polarization sensitive optical coherence tomography for comparison. The highest contrast for near- IR reflectance was at 1460 nm and 1500 - 1700 nm. These near-IR wavelengths are coincident with higher water absorption. The clear Delton sealant investigated was not visible in either co-polarization or crosspolarization OCT images. The wavelength region between 1500-1700-nm yielded the highest contrast of lesions under sealants for near-IR reflectance measurements.

  1. Sphingoid bases inhibit acid-induced demineralization of hydroxyapatite.

    PubMed

    Valentijn-Benz, Marianne; van 't Hof, Wim; Bikker, Floris J; Nazmi, Kamran; Brand, Henk S; Sotres, Javier; Lindh, Liselott; Arnebrant, Thomas; Veerman, Enno C I

    2015-01-01

    Calcium hydroxyapatite (HAp), the main constituent of dental enamel, is inherently susceptible to the etching and dissolving action of acids, resulting in tooth decay such as dental caries and dental erosion. Since the prevalence of erosive wear is gradually increasing, there is urgent need for agents that protect the enamel against erosive attacks. In the present study we studied in vitro the anti-erosive effects of a number of sphingolipids and sphingoid bases, which form the backbone of sphingolipids. Pretreatment of HAp discs with sphingosine, phytosphingosine (PHS), PHS phosphate and sphinganine significantly protected these against acid-induced demineralization by 80 ± 17%, 78 ± 17%, 78 ± 7% and 81 ± 8%, respectively (p < 0.001). On the other hand, sphingomyelin, acetyl PHS, octanoyl PHS and stearoyl PHS had no anti-erosive effects. Atomic force measurement revealed that HAp discs treated with PHS were almost completely and homogeneously covered by patches of PHS. This suggests that PHS and other sphingoid bases form layers on the surface of HAp, which act as diffusion barriers against H(+) ions. In principle, these anti-erosive properties make PHS and related sphingosines promising and attractive candidates as ingredients in oral care products.

  2. Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a case report

    PubMed Central

    2010-01-01

    Cellular therapy for spinal cord injury (SCI) is overviewed focusing on bone marrow mononuclear cells, olfactory ensheathing cells, and mesenchymal stem cells. A case is made for the possibility of combining cell types, as well as for allogeneic use. We report the case of 29 year old male who suffered a crush fracture of the L1 vertebral body, lacking lower sensorimotor function, being a score A on the ASIA scale. Stem cell therapy comprised of intrathecal administration of allogeneic umbilical cord blood ex-vivo expanded CD34 and umbilical cord matrix MSC was performed 5 months, 8 months, and 14 months after injury. Cell administration was well tolerated with no adverse effects observed. Neuropathic pain subsided from intermittent 10/10 to once a week 3/10 VAS. Recovery of muscle, bowel and sexual function was noted, along with a decrease in ASIA score to "D". This case supports further investigation into allogeneic-based stem cell therapies for SCI. PMID:21070647

  3. EDTA-insoluble, calcium-binding proteoglycan in bovine bone

    NASA Technical Reports Server (NTRS)

    Hashimoto, Y.; Lester, G. E.; Caterson, B.; Yamauchi, M.

    1995-01-01

    A calcium ion precipitable, trypsin-generated proteoglycan fragment has been isolated from the demineralized, EDTA-insoluble matrices of bone. The demineralized matrix was completely digested with trypsin, increasing concentrations of CaCl2 were added to the supernatant, and the resulting precipitates were analyzed. The amount of precipitate gradually increased with higher concentrations of calcium and was reversibly solubilized by EDTA. After molecular sieve and anion exchange chromatography, a proteoglycan-containing peak was obtained. Immunochemical analysis showed that this peak contained chondroitin 4-sulfate and possibly keratan sulfate. Amino acid analysis showed that this proteoglycan contained high amounts of aspartic acid/asparagine (Asx), serine (Ser), glutamic acid/glutamine (Glx), proline (Pro), and glycine (Gly); however, it contained little leucine (Leu) which suggests that it is not a member of the leucine-rich small proteoglycan family. In addition, significant amounts of phosphoserine (P-Ser) and hydroxyproline (Hyp) were identified in hydrolysates of this fraction. A single band (M(r) 59 kDa) was obtained on SDS-PAGE that stained with Stains-all but not with Coomassie Brilliant Blue R-250. If bone powder was trypsinized prior to demineralization, this proteoglycan-containing fraction was not liberated. Collectively, these results indicate that a proteoglycan occurs in the demineralized matrix that is precipitated with CaCl2 and is closely associated with both mineral and collagen matrices. Such a molecule might facilitate the structural network for the induction of mineralization in bone.

  4. Iodine-131-metaiodobenzylguanidine therapy with reduced-intensity allogeneic stem cell transplantation in recurrent neuroblastoma.

    PubMed

    Takahashi, Hiroka; Manabe, Atsushi; Aoyama, Chiaki; Kamiya, Takahiro; Kato, Itaru; Takusagawa, Ayako; Ogawa, Chitose; Ozawa, Miwa; Hosoya, Ryota; Yokoyama, Kunihiko

    2008-03-01

    Neuroblastoma is the most common extracranial solid tumor of childhood, and iodine-131-metaiodobenzylguanidine (MIBG) therapy is a new approach for grade IV neuroblastoma. We describe the case history of a 3-year-old girl with recurrent neuroblastoma who received MIBG therapy with reduced-intensity allogeneic stem cell transplantation (RIST) because of an extensive bone marrow involvement. The post-transplant course was uneventful and complete chimerism was obtained. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. The patient remained in remission for 3 months after RIST until the second relapse. MIBG therapy combined with RIST warrants further trials.

  5. Demineralization–remineralization dynamics in teeth and bone

    PubMed Central

    Abou Neel, Ensanya Ali; Aljabo, Anas; Strange, Adam; Ibrahim, Salwa; Coathup, Melanie; Young, Anne M; Bozec, Laurent; Mudera, Vivek

    2016-01-01

    Biomineralization is a dynamic, complex, lifelong process by which living organisms control precipitations of inorganic nanocrystals within organic matrices to form unique hybrid biological tissues, for example, enamel, dentin, cementum, and bone. Understanding the process of mineral deposition is important for the development of treatments for mineralization-related diseases and also for the innovation and development of scaffolds. This review provides a thorough overview of the up-to-date information on the theories describing the possible mechanisms and the factors implicated as agonists and antagonists of mineralization. Then, the role of calcium and phosphate ions in the maintenance of teeth and bone health is described. Throughout the life, teeth and bone are at risk of demineralization, with particular emphasis on teeth, due to their anatomical arrangement and location. Teeth are exposed to food, drink, and the microbiota of the mouth; therefore, they have developed a high resistance to localized demineralization that is unmatched by bone. The mechanisms by which demineralization–remineralization process occurs in both teeth and bone and the new therapies/technologies that reverse demineralization or boost remineralization are also scrupulously discussed. Technologies discussed include composites with nano- and micron-sized inorganic minerals that can mimic mechanical properties of the tooth and bone in addition to promoting more natural repair of surrounding tissues. Turning these new technologies to products and practices would improve health care worldwide. PMID:27695330

  6. Demineralization–remineralization dynamics in teeth and bone

    PubMed Central

    Abou Neel, Ensanya Ali; Aljabo, Anas; Strange, Adam; Ibrahim, Salwa; Coathup, Melanie; Young, Anne M; Bozec, Laurent; Mudera, Vivek

    2016-01-01

    Biomineralization is a dynamic, complex, lifelong process by which living organisms control precipitations of inorganic nanocrystals within organic matrices to form unique hybrid biological tissues, for example, enamel, dentin, cementum, and bone. Understanding the process of mineral deposition is important for the development of treatments for mineralization-related diseases and also for the innovation and development of scaffolds. This review provides a thorough overview of the up-to-date information on the theories describing the possible mechanisms and the factors implicated as agonists and antagonists of mineralization. Then, the role of calcium and phosphate ions in the maintenance of teeth and bone health is described. Throughout the life, teeth and bone are at risk of demineralization, with particular emphasis on teeth, due to their anatomical arrangement and location. Teeth are exposed to food, drink, and the microbiota of the mouth; therefore, they have developed a high resistance to localized demineralization that is unmatched by bone. The mechanisms by which demineralization–remineralization process occurs in both teeth and bone and the new therapies/technologies that reverse demineralization or boost remineralization are also scrupulously discussed. Technologies discussed include composites with nano- and micron-sized inorganic minerals that can mimic mechanical properties of the tooth and bone in addition to promoting more natural repair of surrounding tissues. Turning these new technologies to products and practices would improve health care worldwide.

  7. Effect of cadmium on bone resorption in cultured fetal bone

    SciTech Connect

    Miyahara, T.; Miyakoshi, M.; Kozuka, H.

    1980-08-01

    Itai-itai disease which occurred in Toyama Prefecture, Japan, was thought to be due, at least partly, to chronic cadmium poisoning. Patients suffered severe pain in the waist, back and joints as well as kyphosis spinal column. In addition, x-ray film of these patients revealed abnormalities in the humerus and ribs. These bone lesions have been considered to be caused secondarily by dysfunction of other tissues, especially that of the kidneys, but there are some reports that the bone lesions appear before the occurrence of pathological changes in the kidneys of Cd-administered rat. It is currently unclear whether bone lesions by Cd are due to the direct action on the bone or indirect action which is caused by dysfunction of the kidney or intestine. To clarify the direct action of Cd on the bone, we studied the effect of Cd on the ossification of chick-embryo cultured bones biochemically and histologically. The results showed that Cd inhibited the bone matrix formation and brought about a malfunction in the ossification process. In the present work the effect of Cd on demineralization was studied using /sup 45/Ca-prelabeled bone in tissue culture and low levels of Cd were found to stimulate /sup 45/Ca from the bone.

  8. The effects of immobilization on cortical bone in monkeys (M. nemestrina)

    NASA Technical Reports Server (NTRS)

    Niklowitz, W. J.; Bunch, T. E.; Young, D. R.

    1983-01-01

    Rhesus and pigtail monkeys were restrained for up to seven months in a hypogravic-hypodynamic environment for the purpose of studying the osteoporotic process and its reversibility, particularly in relation to humans. In vivo bending, radiography and tomography are among the techniques that were used. Bone deterioration within one month was detectable only in histological preparation, where resorption and subsequent cavity formation were demonstrated in addition to demineralization of the remaining hard tissue. Norland bone mineral analysis showed the greatest bone demineralization in the proximal tibia (23 percent to 31 percent after six months restraint), recovery did not even necessarily occur after 15 months. The largest bone stiffness decrease was 36 to 40 percent after a six months restraint; normal bending properties but not mineral content were restored after 8-1/2 months. Contrary to earlier studies, it is concluded that bone recovery, though a lengthy process, is possible: cortical bone in the tibia required 40 months.

  9. Postradiation atrophy of mature bone

    SciTech Connect

    Erguen, H.; Howland, W.J.

    1980-01-01

    The growing number of oncological patients subjected to radiotherapy require the diagnostic radiologist to be aware of expected bone changes following irradiation and the differentiation of this entity from metastasis. The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing, mainly because of the relative insensitivity of radiographs in detecting demineralization. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. In vivo midrodensitometric analysis and radionuclide bone and bone marrow scans can reveal early changes following irradiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.

  10. Postradiation atrophy of mature bone

    SciTech Connect

    Ergun, H.; Howland, W.J.

    1980-01-01

    The growing number of oncological patients subjected to radiotherapy require the diagnostic radiologist to be aware of expected bone changes following irradiation and the differentiation of this entity from metastasis. The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing, mainly because of the relative insensitivity of radiographs in detecing demineralization. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. In vivo midrodensitometric analysis and radionuclide bone and bone marrow scans can reveal early changes following irradiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.

  11. Nanocomposites and bone regeneration

    NASA Astrophysics Data System (ADS)

    James, Roshan; Deng, Meng; Laurencin, Cato T.; Kumbar, Sangamesh G.

    2011-12-01

    This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

  12. [Prolonged acute pancreatitis after bone marrow transplantation].

    PubMed

    De Singly, B; Simon, M; Bennani, J; Wittnebel, S; Zagadanski, A-M; Pacault, V; Gornet, J-M; Allez, M; Lémann, M

    2008-04-01

    Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids.

  13. Psychosocial adjustment of pediatric patients after allogeneic stem cell transplantation.

    PubMed

    Felder-Puig, R; Peters, C; Matthes-Martin, S; Lamche, M; Felsberger, C; Gadner, H; Topf, R

    1999-07-01

    The purpose of this study was to assess the psychosocial adjustment of patients who had been treated with allogeneic stem cell transplantation (SCT) in our clinic. Selection criteria for patients were to be aged 14-30 years at the time of the follow-up, to be at least 2 years post-SCT and to have a very good knowledge of German. Among 31 eligible patients, 26 participated (84% response rate). The patients were between 15 and 27 years old and were on average 7 years (range 2-13) post-SCT. Research instruments consisted of a demographic questionnaire and various subscales of established psychological measures for which data from a sample of bone cancer survivors and population norms were available. About 35% of patients showed high levels of anxiety, 62% appeared to be extremely sensitive and vulnerable, and 35% showed strong, unfulfilled needs in their love lives. In the other domains tested (self-esteem, family and peer relationships, school/vocational performance, etc), no noticeable differences were found between the subjects and comparable populations. There was no significant association between psychosocial outcome and demographic features or clinical data. Our results suggest that patients who underwent SCT in their childhood or adolescence are at risk of developing long-term emotional or social problems. Due to the retrospective design of our study and the small sample size, no predictive factors for psychosocial distress could be identified.

  14. [Human Herpesvirus-6 Encephalitis in Allogeneic Hematopoietic Stem Cell Transplantation].

    PubMed

    Ogata, Masao

    2015-07-01

    The reactivation of human herpesvirus-6B (HHV-6B) is common after allogeneic hematopoietic cell transplantation (allo-HCT), and it is sporadically associated with the development of HHV-6 encephalitis. HHV-6 encephalitis typically develops around 2-6 weeks after allo-HCT, and it is characterized by short-term memory loss. Magnetic resonance imaging typically shows bilateral signal abnormalities in the limbic system. The incidence of HHV-6 encephalitis is reportedly 0-11.6% after bone marrow or peripheral blood stem cell transplantation and 4.9-21.4% after cord blood transplantation. The mortality of HHV-6 encephalitis is high, and survivors are often left with serious sequelae. Antiviral therapy using foscarnet or ganciclovir is recommended for the treatment of HHV-6 encephalitis, but the efficacy of the currently available treatment is insufficient once HHV-6 encephalitis has developed. The elucidation of the pathogenesis of HHV-6 encephalitis and the establishment of preventative therapy are needed to overcome this disease.

  15. Development of a process flowsheet for the elution of radiocesium from the TMI-2 makeup and purification demineralizers. Volume 2

    SciTech Connect

    Bond, W D; Knauer, J B; King, L J

    1986-09-01

    A process was developed for removing radiocesium from the two makeup and purification demineralizers at TMI-2 which had been highly contaminated as a result of the accident in 1979. Process conditions were established in hot-cell experiments using relatively small samples of the contaminated and degraded resins from the TMI-2 demineralizers.

  16. Heterotopic new bone formation causes resorption of the inductive bone matrix

    SciTech Connect

    Nilsson, O.S.; Persson, P.E.; Ekelund, A. )

    1990-08-01

    The bone matrix of growing rats was labeled by multiple injections of 3H-proline, and demineralized bone matrix (DBM) was prepared. The DBM was allotransplanted heterotopically into growing rats. New bone formation was induced in and around the implants. The new bone formation was accompanied by a decrease in the content of 3H; 20 and 30 days after implantation, 72% and 46%, respectively, of the activity remained in the implants. Daily injections of indomethacin (2 mg/kg) inhibited calcium uptake by about 20% at 20 and 30 days and inhibited the release of 3H from the DBM to a similar degree. Heterotopic bone induction by DBM is accompanied by matrix resorption, and inhibition of the new bone formation decreases the resorption of DBM.

  17. [Successful treatment of an overwhelming infection with granulocyte transfusion in severe aplastic anemia patient undergoing allogeneic peripheral blood stem cell transplantation].

    PubMed

    Kazuma, Yasuhiro; Ono, Yuichiro; Yonetani, Noboru; Imai, Yukihiro; Kawakami, Manabu; Hashimoto, Hisako; Ishikawa, Takayuki

    2016-04-01

    A 19-year-old woman complaining of fever and a sore throat was diagnosed with very severe aplastic anemia (AA) by bone marrow examination at a local hospital. Despite administration of antibiotics and granulocyte-colony stimulating factor to treat the soft tissue infection in her neck, her neutrophil count showed no increase. Because emergent allogeneic stem cell transplantation (SCT) was necessary, she was referred to our hospital. On admission, computed tomography revealed right-sided severe pharyngitis and lymphadenitis causing tracheal stenosis, and emergent intubation was required the next day. Granulocyte transfusion therapy (GTX) from related donors coupled with broad-spectrum antibiotic administration controlled the otherwise overwhelming infection. The patient received allogeneic peripheral blood SCT using a reduced-intensity conditioning regimen. After allogeneic SCT, successful engraftment was obtained. She was discharged from the hospital 59 days after allogeneic SCT. She remains alive and well, as of the latest follow up. This case clearly demonstrates that GTX is useful for controlling severe infection and enables patients with severe AA to receive allogeneic SCT safely. PMID:27169447

  18. Biologic augmentation of foot and ankle arthrodeses with an allogeneic cancellous sponge.

    PubMed

    Protzman, Nicole M; Galli, Melissa M; Bleazey, Scott T; Brigido, Stephen A

    2014-03-01

    This case series was conducted to assess the safety and efficacy of using an allogeneic cancellous bone sponge for augmentation of foot and ankle arthrodeses. Twenty-five patients were prospectively enrolled in the study prior to undergoing fusion and were then followed for 12 months postoperatively. There were 45 joints: 7 ankles, 12 subtalars, 12 talonaviculars, 6 calcaneocuboids, 1 naviculocuneiform, 6 first tarsometatarsals, and 1 second tarsometatarsal. Patient-reported outcomes of pain (visual analog scale) and function (American Orthopaedic Foot and Ankle Society score) were obtained preoperatively and postoperatively at 6 and 12 months. No complications were noted intraoperatively or during the follow-up period. Three months postoperatively, radiographic osseous union was noted in 52% (13/25) of patients, which further increased to 96% (24/25) of patients at 6 and 12 months. There was no statistically significant difference in union time between joints [H(6)=11.5; P=.08]. Statistically significant improvements in pain (P≤.002) and function (P<.001) were observed across assessments. This study demonstrated that the cancellous bone sponge appears to be a safe and efficacious product. Randomized controlled trials are warranted to determine if the allogeneic cancellous sponge improves fusion rate, pain, and function.

  19. The Digital Astronaut Project Bone Remodeling Model

    NASA Technical Reports Server (NTRS)

    Pennline, James A.; Mulugeta, Lealem; Lewandowski, Beth E.; Thompson, William K.; Sibonga, Jean D.

    2014-01-01

    Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur: (1) The most commonly used countermeasure against bone loss has been prescribed exercise, (2) However, current exercise countermeasures do not completely eliminate bone loss in long duration, 4 to 6 months, spaceflight, (3,4) leaving the astronaut susceptible to early onset osteoporosis and a greater risk of fracture later in their lives. The introduction of the Advanced Resistive Exercise Device, coupled with improved nutrition, has further minimized the 4 to 6 month bone loss. But further work is needed to implement optimal exercise prescriptions, and (5) In this light, NASA's Digital Astronaut Project (DAP) is working with NASA physiologists to implement well-validated computational models that can help understand the mechanisms of bone demineralization in microgravity, and enhance exercise countermeasure development.

  20. Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs

    SciTech Connect

    Grosse-Wilde, H.; Krumbacher, K.; Schuening, F.D.; Doxiadis, I.; Mahmoud, H.K.; Emde, C.; Schmidt-Weinmar, A.; Schaefer, U.W.

    1986-07-01

    Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. It could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells.

  1. Effects of a buried magnetic field on cranial bone reconstruction in rats

    PubMed Central

    de ABREU, Maíra Cavallet; PONZONI, Deise; LANGIE, Renan; ARTUZI, Felipe Ernesto; PURICELLI, Edela

    2016-01-01

    ABSTRACT The understanding of bone repair phenomena is a fundamental part of dentistry and maxillofacial surgery. Objective The present study aimed to evaluate the influence of buried magnetic field stimulation on bone repair in rat calvaria after reconstruction with autogenous bone grafts, synthetic powdered hydroxyapatite, or allogeneic cartilage grafts, with or without exposure to magnetic stimulation. Material and Methods Ninety male Wistar rats were divided into 18 groups of five animals each. Critical bone defects were created in the rats’ calvaria and immediately reconstructed with autogenous bone, powdered synthetic hydroxyapatite or allogeneic cartilage. Magnetic implants were also placed in half the animals. Rats were euthanized for analysis at 15, 30, and 60 postoperative days. Histomorphometric analyses of the quantity of bone repair were performed at all times. Results These analyses showed significant group by postoperative time interactions (p=0.008). Among the rats subjected to autogenous bone reconstruction, those exposed to magnetic stimulation had higher bone fill percentages than those without magnetic implants. Results also showed that the quality of bone repair remained higher in the former group as compared to the latter at 60 postoperative days. Conclusions After 60 postoperative days, bone repair was greater in the group treated with autogenous bone grafts and exposed to a magnetic field, and bone repair was most pronounced in animals treated with autogenous bone grafts, followed by those treated with powdered synthetic hydroxyapatite and allogeneic cartilage grafts. PMID:27119765

  2. Systematic Nutritional Support in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

    PubMed

    Fuji, Shigeo; Einsele, Hermann; Savani, Bipin N; Kapp, Markus

    2015-10-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) has become an established treatment modality for various hematological diseases. However, in allogeneic HSCT, patients often suffer from severe gastrointestinal complications caused by the conditioning regimen and acute/chronic graft-versus-host disease, which requires support by multidisciplinary nutritional support teams (NST). In addition, pretransplantation nutritional status can affect the clinical outcome after allogeneic HSCT. Therefore, it is important to refer the patient to a NST when becoming aware of nutritional problems before allogeneic HSCT. It is also important to follow nutritional status over the long term, as patients often suffer from various nutritional problems, such as malnutrition and metabolic syndrome, even late after allogeneic HSCT. In summary, NST can contribute to the improvement of nutritional status and possibly prognosis at every stage before and after allogeneic HSCT. Here, we aim to give a comprehensive overview of current understanding about nutritional support in allogeneic HSCT and try to provoke a constructive discussion to stimulate further investigation.

  3. UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

    SciTech Connect

    Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A. )

    1990-05-01

    Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms.

  4. A three-species biofilm model for the evaluation of enamel and dentin demineralization.

    PubMed

    Cavalcanti, Yuri Wanderley; Bertolini, Martinna Mendonça; da Silva, Wander José; Del-Bel-Cury, Altair Antoninha; Tenuta, Livia Maria Andaló; Cury, Jaime Aparecido

    2014-01-01

    Although Streptococcus mutans biofilms have been useful for evaluating the cariogenic potential of dietary carbohydrates and the effects of fluoride on dental demineralization, a more appropriate biofilm should be developed to demonstrate the influence of other oral bacteria on cariogenic biofilms. This study describes the development and validation of a three-species biofilm model comprising Streptococcus mutans, Actinomyces naeslundii, and Streptococcus gordonii for the evaluation of enamel and dentin demineralization after cariogenic challenges and fluoride exposure. Single- or three-species biofilms were developed on dental substrata for 96 h, and biofilms were exposed to feast and famine episodes. The three-species biofilm model produced a large biomass, mostly comprising S. mutans (41%) and S. gordonii (44%), and produced significant demineralization in the dental substrata, although enamel demineralization was decreased by fluoride treatment. The findings indicate that the three-species biofilm model may be useful for evaluating the cariogenic potential of dietary carbohydrates other than sucrose and determining the effects of fluoride on dental substrata.

  5. Pulse thermography for quantitative nondestructive evaluation of sound, de-mineralized and re-mineralized enamel

    NASA Astrophysics Data System (ADS)

    Ando, Masatoshi; Sharp, Nathan; Adams, Douglas

    2012-04-01

    Current limitations for diagnosing mineralization state of tooth enamel can lead to improper surgical treatments. A method is investigated by which the tooth health state is characterized according to its thermal response, which is hypothesized to be sensitive to increased porosity in enamel that is caused by demineralization. Several specimens consisting of previously extracted human teeth a re prepared by exposure to Streptococcus mutans A32-2 in trypticase-soy-borth supplemented with 5% sucrose at 37°C for 3 or 6 days to de-mineralize two 1×1mm2-windows on each tooth. One of these windows is then re-mineralized with 250 or 1,100ppm-F as NaF for 10 days by pH-cyclic-model. Pulse thermography is used to measure the thermal response of these sections as well as the sound (healthy) portions of the specimen. A spatial profile of the thermal parameters of the specimens is then extracted from the thermography data and are used to compare the sound, de-mineralized, and re-mineralized areas. Results show that the thermal parameters are sensitive to the mineralization state of the tooth and that this method has the potential to accurately and quickly characterize the mineralization state of teeth, thereby allowing future dentists to make informed decisions regarding the best treatment for teeth that have experienced demineralization.

  6. DEMINERALIZER BUILDING, TRA608. CATION AND ANION EXCHANGERS LINE UP ALONG ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DEMINERALIZER BUILDING, TRA-608. CATION AND ANION EXCHANGERS LINE UP ALONG NORTH WALL ON CONCRETE PLATFORMS. INL NEGATIVE NO. 2527. Unknown Photographer, 6/12/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  7. A&M. Demineralization plant, TAN649. Floor plan, elevation details. Ralph M. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    A&M. Demineralization plant, TAN-649. Floor plan, elevation details. Ralph M. Parsons 1480-4-ANP/GE-3-649-A-1. Date: October 1958. Approved by INEEL Classification Office for public release. INEEL index code no. 034-0649-00-693-107439 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

  8. Comparative analysis of optical coherence tomography signal and microhardness for demineralization evaluation of human tooth enamel

    NASA Astrophysics Data System (ADS)

    de Cara, Ana Claudia Ballet; Zezell, Denise Maria; Ana, Patricia A.; Deana, Alessandro Melo; Amaral, Marcello Magri; Dias Vieira, Nilson, Jr.; de Freitas, Anderson Zanardi

    2012-06-01

    The diagnosis of dental caries at an early stage enables the implementation of conservative treatments based on dental preservation. Several diagnostic methods have been developed, like visual-tactile and radiographic are the most commons but are limited for this application. The Optical Coherence Tomography is a technique that provides information of optical properties of enamel, which may change due to the decay process. The objective of this study was to evaluate the ability of OCT to detect different stages of demineralization of tooth enamel during the development of artificial caries lesions, taking as a reference standard for comparison sectional microhardness testing. Different stages of caries lesions were simulated using the pH cycling model suggested Feathestone and modified by Argenta. The samples were exposed to 0 (control group), 5, 10, 15, 20 and 25 days at a daily regimen of three hours demineralization followed by remineralization during 20 hours. It was used an OCT system with at 930nm. Sectional images were generated in all lesion region. The results obtained from the OCT technique presented similar behavior to microhardness, except for the group 25 days, due to inability to perform indentations reading in areas of more intense demineralization. A linear relationship was observed between the OCT and microhardness techniques for detection of demineralization in enamel. This relationship will allow the use of OCT technique in quantitative assessment of mineral loss and for the evaluation of incipient caries lesions.

  9. Tensile Strength of Mineralized/Demineralized Human Normal and Carious Dentin

    PubMed Central

    Nishitani, Y.; Yoshiyama, M.; Tay, F.R.; Wadgaonkar, B.; Waller, J.; Agee, K.; Pashley, D.H.

    2006-01-01

    The bond strengths of resins to caries-affected dentin are low. This could be due to weakened organic matrix. The purpose of this work was to determine if the ultimate tensile strength (UTS) of excavated carious dentin is weaker than that of normal dentin. Soft caries was excavated from extracted human molars, and the tooth was vertically sectioned into slabs. Each slab was trimmed to an hourglass shape, parallel or perpendicular to the tubule direction. Half of the specimens were mineralized, while the other half were completely demineralized in EDTA. ANOVA on ranks showed that the three-factor interactions (mineralization, caries, tubule direction) were all significant (p < 0.0001), indicating that mineralization and tubule direction gave different UTS results in normal and caries-affected dentin. No significant differences were seen between the UTS of normal and and that of caries-affected demineralized dentin in the parallel or perpendicular group. The matrix of demineralized caries-affected dentin was as strong as that of normal demineralized dentin when tested in the same direction. PMID:16246945

  10. Effects of ammonium hexafluorosilicate application on demineralized enamel and dentin of primary teeth.

    PubMed

    Hosoya, Yumiko; Watanabe, Eiko; Tadokoro, Katsumi; Inoue, Takashi; Miyazaki, Masashi; Tay, Franklin R

    2012-09-01

    Silver diamine fluoride (Ag(NH(3))(2)F) arrests caries but stains teeth black. To overcome this drawback, we applied ammonium hexafluorosilicate (AHF; (NH(4))(2)SiF(6)) and observed changes in the color and structure of demineralized enamel and dentin of extracted primary teeth. Enamel and dentin were demineralized in 10% EDTA solution for 90 s followed by 35% phosphoric acid gel for 60 s, then soaked in AHF solution for 60 s. Before analysis by scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDS), enamel and dentin were demineralized in 10% EDTA for 90 s. Teeth were divided into 4 groups according to AHF application and artificial saliva immersion status and then examined. The data were statistically analyzed using one-way ANOVA and Fisher's PLSD test at a significance level of P < 0.05. AHF treatment did not cause visible discoloration. Enamel prisms and dental tubules appeared by demineralization were covered with precipitates by AHF application. A sphere-filled membranous structure was observed in the saliva immersion groups. EDS analysis showed that AHF application had no effect on enamel; however, F% and Ca/P ratio were significantly higher on dentin surfaces after AHF application without artificial saliva immersion. Further study on arresting caries treatment is required. PMID:23047038

  11. Prevention of enamel demineralization with a novel fluoride strip: enamel surface composition and depth profile

    PubMed Central

    Lee, Bor-Shiunn; Chou, Po-Hung; Chen, Shu-Yu; Liao, Hua-Yang; Chang, Che-Chen

    2015-01-01

    There is no topically applicable low concentration fluoride delivery device available for caries prevention. This study was aimed to assess the use of a low concentration (1450 ppm) fluoride strip as an effective fluoride delivery system against enamel demineralization. The enamel surface composition and calcium-deficient hydroxyapatite or toothpaste treatments were investigated using X-ray photoelectron spectroscopy. In vitro enamel demineralization was assayed using a pH cycling model and the dissolution of calcium ions from the treated specimens was quantified using ion chromatography. After 24-hr fluoride-strip treatment, the enamel was covered with a CaF2 layer which showed a granular morphology of 1 μm in size. Below the CaF2 layer was a region of mixed fluorapatite and CaF2. Fluoride infiltrated extensively in enamel to produce highly fluorinated fluorohydroxyapatite. In comparison, low-fluoride-level fluorinated fluorohydroxyapatite was formed on the enamel specimen exposed to toothpaste. The treatments with the fluoride strip as short as 1 hr significantly inhibited enamel demineralization. The fluoride strip was effective for topical fluoride delivery and inhibited in vitro demineralization of enamel by forming CaF2 and fluoride-containing apatites at the enamel surface. It exhibited the potential as an effective fluoride delivery device for general use in prevention of caries. PMID:26293361

  12. Assessing bone loss in micro-gravity: a fuzzy approach.

    PubMed

    Zobel, Bruno Beomonte; Del Vescovo, Riccardo; Oliva, Gabriele; Russo, Valentina; Setola, Roberto

    2012-12-01

    A prolonged stay in microgravity has various negative effects on the human body; one of these problems is a noticeable demineralization of bone tissues. Such effects are quite similar to those experienced by subjects on earth affected by osteoporosis; therefore it seems quite straightforward to adopt a similar pharmacological therapy during the stay in the space. In this paper a first step in the identification of a monitoring procedure for the bone demineralization in microgravity, as well as some guidelines for the choice of adequate therapies are given. Such a procedure is based on a mathematical model of the interaction of the most relevant blood and urine indicators of bone demineralization. Specifically, some bone metabolites have been identified, which are relevant to the phenomena and are feasible to be evaluated in the space. Moreover, a model to foresee the evolution of these parameters in the space, depending on the therapy chosen, is provided. The model is derived from the experience of doctors and experts, hence it is based mainly on linguistic information; such an information is codified by means of fuzzy numbers, in order to take into account their uncertainty.

  13. Thermal stabilization of collagen in skin and decalcified bone

    NASA Astrophysics Data System (ADS)

    Miles, Christopher A.; Avery, Nicholas C.

    2011-04-01

    The state of collagen molecules in the fibres of tail tendon, skin and demineralized bone has been investigated in situ using differential scanning calorimetry (DSC). Hydroxyproline analysis and tissue digestion with bacterial collagenase and trypsin were used to confirm that the common cause of all the DSC endotherms was collagen denaturation. This occurred within a narrow temperature range in tendons, but over a wide temperature range in demineralized bone and old skin and demonstrated that in tendon and demineralized bone at least the same type I collagen molecule exists in different thermal states. Hypothesizing that this might be caused by different degrees of confinement within the fibre lattice, experiments were performed to measure the effect of changing the lattice dimensions by extracting the collagen into dilute solution with pepsin, swelling the lattice in acetic acid, and contracting the lattice by dehydration. A theoretical analysis was undertaken to predict the effect of dehydration. Results were consistent with the hypothesis, demonstrating that collagen molecules within the natural fibres of bone and old skin are located at different intermolecular spacings, revealing differences between molecules in the magnitude of either the attractive or repulsive forces controlling their separation. One potential cause of such variation is known differences in covalent cross-linking.

  14. In vitro evaluation of the efficacy of laser fluorescence (DIAGNOdent) to detect demineralization and remineralization of smooth enamel lesions

    PubMed Central

    Bahrololoomi, Zahra; Musavi, Seyed Ahmad; Kabudan, Mona

    2013-01-01

    Objective: Early detection of smooth surface lesions is important for appropriate management and monitoring of dental caries. The purpose of this in vitro study was to evaluate the efficacy of laser fluorescence to detect demineralization and remineralization of smooth enamel surfaces. Materials and Methods: In this in vitro study, 132 enamel blocks of semi-impacted human third molars were obtained; artificial caries lesions were induced and they were submitted to the pH-cycling process to create remineralization. Superficial microhardness (SMH) and laser fluorescence (LF) analysis were performed at baseline, after demineralization, and remineralization processes. The data were analyzed by Statistical Package for Social Sciences (SPSS)-16 using analysis of variance (ANOVA), Paired samples t-test, and Pearson's correlation test. Results: There was a significant difference between SMH values at baseline, after demineralization and after remineralization. Also, a statistically significant difference was observed between LF values in these three stages. The LF values increased after demineralization and then decreased after remineralization, and the SMH values decreased after demineralization and increased after remineralization. There was an inverse relationship between SMH and LF only at baseline and after demineralization, but not after remineralization. Conclusion: The results showed that LF is an appropriate method for detection of demineralization in an in vitro condition in smooth enamel lesions, but it was not so efficient in the detection of remineralization. PMID:23956542

  15. Near-IR Image-Guided Laser Ablation of Demineralization on Tooth Occlusal Surfaces

    PubMed Central

    Tom, Henry; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

    2016-01-01

    Introduction Studies have shown that reflectance images at near-IR wavelengths coincident with higher water absorption are well-suited for image-guided laser ablation of carious lesions since the contrast between sound and demineralized enamel is extremely high and interference from stains is minimized. The objective of this study was to demonstrate that near-IR reflectance images taken at a wavelength range of 1,500–1,700 nm can be used to guide a 9.3 μm CO2 laser for the selective ablation of early demineralization on tooth occlusal surfaces. Methods The occlusal surfaces of ten sound human molars were used in this in vitro study. Shallow simulated caries lesions with random patterns and varying depth and position were produced on tooth occlusal surfaces. Sequential near-IR reflectance images at 1,500–1,700 nm were used to guide the laser for the selective removal of the demineralized enamel. Digital microscopy and polarization sensitive optical coherence tomography (PS-OCT) were used to assess selectivity. Results Images taken before and after lesion removal suggest that the demineralized areas were removed with high selectivity. Although the estimated volume of tissue ablated was typically higher than the initial lesion volume measured with PS-OCT, the volume of enamel removed by the laser correlated well with the initial lesion volume. Conclusion Sequential near-IR reflectance images at 1,500–1,700 nm can be used to guide a 9.3 μm CO2 laser for the selective ablation of early demineralization on tooth occlusal surfaces. PMID:26763111

  16. Combining CPP-ACP with fluoride: a synergistic remineralization potential of artificially demineralized enamel or not?

    NASA Astrophysics Data System (ADS)

    El-Sayad, I. I.; Sakr, A. K.; Badr, Y. A.

    2008-08-01

    Background and objective: Minimal intervention dentistry (MID) calls for early detection and remineralization of initial demineralization. Laser fluorescence is efficient in detecting changes in mineral tooth content. Recaldent is a product of casein phosphopeptide-amorphous calcium phosphate (CPP- ACP) which delivers calcium and phosphate ions to enamel. A new product which also contains fluoride is launched in United States. The remineralizing potential of CPP- ACP per se, or when combined with 0.22% Fl supplied in an oral care gel on artificially demineralised enamel using laser fluorescence was investigated. Methods: Fifteen sound human molars were selected. Mesial surfaces were tested using He-Cd laser beam at 441.5nm with 18mW power as excitation source on a suitable set-up based on Spex 750 M monochromator provided with PMT for detection of collected auto-fluorescence from sound enamel. Mesial surfaces were subjected to demineralization for ten days. The spectra from demineralized enamel were measured. Teeth were then divided according to the remineralizing regimen into three groups: group I recaldent per se, group II recaldent combined with fluoride gel and group III artificial saliva as a positive control. After following these protocols for three weeks, the spectra from remineralized enamel from the three groups were measured. The spectra of enamel auto-fluorescence were recorded and normalized to peak intensity at about 540 nm to compare between spectra from sound, demineralized and remineralized enamel surfaces. Results: A slight red shift was noticed in spectra from demineralized enamel, while a blue shift may occur in remineralized enamel. Group II showed the highest remineralizing potential. Conclusions: Combining fluoride with CPP-ACP had a synergistic effect on enamel remineralization. In addition, laser auto-fluorescence is an accurate technique for assessment of changes in tooth enamel minerals.

  17. Does collagen trigger the recruitment of osteoblasts into vacated bone resorption lacunae during bone remodeling?

    PubMed

    Abdelgawad, Mohamed Essameldin; Søe, Kent; Andersen, Thomas Levin; Merrild, Ditte M H; Christiansen, Peer; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie

    2014-10-01

    Osteoblast recruitment during bone remodeling is obligatory to re-construct the bone resorbed by the osteoclast. This recruitment is believed to be triggered by osteoclast products and is therefore likely to start early during the remodeling cycle. Several osteoclast products with osteoblast recruitment potential are already known. Here we draw the attention on the osteoblast recruitment potential of the collagen that is freshly demineralized by the osteoclast. Our evidence is based on observations on adult human cancellous bone, combined with in vitro assays. First, freshly eroded surfaces where osteoblasts have to be recruited show the presence of non-degraded demineralized collagen and close cell-collagen interactions, as revealed by electron microscopy, while surface-bound collagen strongly attracts osteoblast lineage cells in a transmembrane migration assay. Compared with other extracellular matrix molecules, collagen's potency was superior and only equaled by fibronectin. Next, the majority of the newly recruited osteoblast lineage cells positioned immediately next to the osteoclasts exhibit uPARAP/Endo180, an endocytic collagen receptor reported to be involved in collagen internalization and cell migration in various cell types, and whose inactivation is reported to lead to lack of bone formation and skeletal deformities. In the present study, an antibody directed against this receptor inhibits collagen internalization in osteoblast lineage cells and decreases to some extent their migration to surface-bound collagen in the transmembrane migration assay. These complementary observations lead to a model where collagen demineralized by osteoclasts attracts surrounding osteoprogenitors onto eroded surfaces, and where the endocytic collagen receptor uPARAP/Endo180 contributes to this migration, probably together with other collagen receptors. This model fits recent knowledge on the position of osteoprogenitor cells immediately next to remodeling sites in adult

  18. Present and Future of Allogeneic Natural Killer Cell Therapy

    PubMed Central

    Lim, Okjae; Jung, Mi Young; Hwang, Yu Kyeong; Shin, Eui-Cheol

    2015-01-01

    Natural killer (NK) cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation revealed the antitumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions. PMID:26089823

  19. Pathogenesis of bone loss after total hip arthroplasty.

    PubMed

    Rubash, H E; Sinha, R K; Shanbhag, A S; Kim, S Y

    1998-04-01

    Bone loss with or without evidence of aseptic loosening is a long term complication after total hip arthroplasty (THA). It occurs with all materials and in all prosthetic systems in use or that have been used to date. Bone loss after THA can be a serious problem in revision surgery because bone deficiencies may limit reconstructive options, increase the difficulty of surgery, and necessitate autogenous or allogenic bone grafting. There are three factors adversely affecting maintenance of bone mass after THA: (1) bone loss secondary to particulate debris; (2) adaptive bone remodeling and stress shielding secondary to size, material properties, and surface characteristics of contemporary prostheses; and (3) bone loss as a consequence of natural aging. This chapter reviews the mechanisms of the primary causes of bone loss after THA.

  20. Near-surface structural examination of human tooth enamel subject to in vitro demineralization and remineralization

    NASA Astrophysics Data System (ADS)

    Gaines, Carmen Veronica

    The early stages of chemical tooth decay are governed by dynamic processes of demineralization and remineralization of dental enamel that initiates along the surface of the tooth. Conventional diagnostic techniques lack the spatial resolution required to analyze near-surface structural changes in enamel at the submicron level. In this study, slabs of highly-polished, decay-free human enamel were subjected to 0.12M EDTA and buffered lactic acid demineralizing agents and MI Paste(TM) and calcifying (0.1 ppm F) remineralizing treatments in vitro. Grazing incidence x-ray diffraction (GIXD), a technique typically used for thin film analysis, provided depth profiles of crystallinity changes in surface enamel with a resolution better than 100 nm. In conjunction with nanoindentation, a technique gaining acceptance as a means of examining the mechanical properties of sound enamel, these results were corroborated with well-established microscopy and Raman techniques to assess the nanohardness, morphologies and chemical nature of treated enamel. Interestingly, the average crystallite size of surface enamel along its c-axis dimension increased by nearly 40% after a 60 min EDTA treatment as detected by GIXD. This result was in direct contrast to the obvious surface degradation observed by microscopic and confocal Raman imaging. A decrease in nanohardness from 4.86 +/- 0.44 GPa to 0.28 +/- 0.10 GPa was observed. Collective results suggest that mineral dissolution characteristics evident on the micron scale may not be fully translated to the nanoscale in assessing the integrity of chemically-modified tooth enamel. While an intuitive decrease in enamel crystallinity was observed with buffered lactic acid-treated samples, demineralization was too slow to adequately quantify the enamel property changes seen. MI Paste(TM) treatment of EDTA-demineralized enamel showed preferential growth along the a-axis direction. Calcifying solution treatments of both demineralized sample types

  1. Acid demineralization susceptibility of dental enamel submitted to different bleaching techniques and fluoridation regimens.

    PubMed

    Salomão, Dlf; Santos, Dm; Nogueira, Rd; Palma-Dibb, Rg; Geraldo-Martins, Vr

    2014-01-01

    The aim of the current study was to assess the acid demineralization susceptibility of bleached dental enamel submitted to different fluoride regimens. One hundred bovine enamel blocks (6×6×3 mm) were randomly divided into 10 groups (n=10). Groups 1 and 2 received no bleaching. Groups 3 to 6 were submitted to an at-home bleaching technique using 6% hydrogen peroxide (HP; G3 and G4) or 10% carbamide peroxide (CP; G5 and G6). Groups 7 to 10 were submitted to an in-office bleaching technique using 35% HP (G7 and G8) or 35% CP (G9 and G10). During bleaching, a daily fluoridation regimen of 0.05% sodium fluoride (NaF) solution was performed on groups 3, 5, 7, and 9, while weekly fluoridation with a 2% NaF gel was performed on groups 4, 6, 8, and 10. The samples in groups 2 to 10 were pH cycled for 14 consecutive days. The samples from all groups were then assessed by cross-sectional Knoop microhardness at different depths from the outer enamel surface. The average Knoop hardness numbers (KHNs) were compared using one-way analysis of variance and Tukey tests (α=0.05). The comparison between groups 1 and 2 showed that the demineralization method was effective. The comparison among groups 2 to 6 showed the same susceptibility to acid demineralization, regardless of the fluoridation method used. However, the samples from groups 8 and 10 showed more susceptibility to acid demineralization when compared with group 2 (p<0.05). Groups 7 and 9 provided similar results to group 2, but the results of those groups were different when compared with groups 8 and 10. The use of 6% HP and 10% CP associated with daily or weekly fluoridation regimens did not increase the susceptibility of enamel to acid demineralization. However, the use of 35% HP and 35% CP must be associated with a daily fluoridation regimen, otherwise the in-office bleaching makes the bleached enamel more susceptible to acid demineralization.

  2. Presumptive invasive Chrysosporium infection in a bone marrow transplant recipient.

    PubMed

    Warwick, A; Ferrieri, P; Burke, B; Blazar, B R

    1991-10-01

    Chrysosporium species caused an invasive infection in an 18-year-old patient following allogeneic sibling bone marrow transplant for T lineage acute lymphoblastic leukemia. This infection began as a facial swelling and extended into the central nervous system. Fungal disease spread rapidly despite antifungal agents. An autopsy showed fungal involvement of brain, lungs, liver and kidneys.

  3. [Conservation and destruction of autologous and allogeneic cryopreserved cellular products: recommendations from the SFGM-TC].

    PubMed

    Calmels, B; Boulanger, F; Baudoux, E; Decot, V; Fawaz, A; Giraud, C; Hivert, B; Garderet, L; Milpied, N; Yakoub-Agha, I

    2014-08-01

    Thousands of autologous and at less extent allogeneic hematopoietic stem cells (HSC) bags are cryopreserved in France. The majority of autologous HSC grafts are used within a year after collection. However, many bags are still unused and cryopreserved for many years. In France and on a European scale, the ever-growing number of cryopreserved bags represents a real economic health concern. Indeed, the cost of storage is about 100€ per bag and per year. In addition, quality and therapeutic value of these long-term cryopreserved grafts needs to be evaluated. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from its member centers across France. These workshops took place in September 2013 in Lille. In this article, we addressed the issue of the destruction of long-term cryopreserved grafts be them autologous or allogeneic and provide recommendations regarding their destruction. PMID:24996844

  4. Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR.

    PubMed

    Mizutani, M; Hara, M; Fujita, H; Aoki, J; Kanamori, H; Ohashi, K; Usuki, K; Fukuda, T; Chou, T; Tanaka, J; Atsuta, Y; Takami, A

    2016-05-01

    Although allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling donor (MSD) is a potentially curative post-remission treatment for adults with acute myeloid leukemia (AML) in their first CR, transplant-related morbidity and mortality remains a major drawback. We retrospectively compared the outcomes of patients who underwent autologous peripheral blood stem cell transplantation (auto-PBSCT; n=375) with those who underwent allogeneic bone marrow transplantation (allo-BMT; n=521) and allo-PBSCT (n=380) from MSDs for adults with AML/CR1, in which propensity score models were used to adjust selection biases among patients, primary physicians and institutions to overcome ambiguity in the patients' background information. Both the multivariate analysis and propensity score models indicated that the leukemia-free survival rate of auto-PBSCT was not significantly different from that of allo-BMT (hazard ratio (HR), 1.23; 95% confidence interval (CI), 0.92 to 1.66; P=0.16) and allo-PBSCT (HR, 1.13; 95% CI, 0.85-1.51; P=0.40). The current results suggest that auto-PBSCT remains a promising alternative treatment for patients with AML/CR1 in the absence of an available MSD. PMID:26808566

  5. [Influence of obstetric factors on the quality of cord blood units collected for allogeneic transplantation].

    PubMed

    Atanassova, V; Atanassova, M; Nikolov, A; Zlatkov, V; Mihaylova, A; Naumova, E

    2012-01-01

    Umbilical cord blood (CB) as a source of haematopoietic stem cells for allogeneic transplantation has many advantages over bone marrow and peripheral blood, however, a main limitation to its use in clinical setting is cell numbers. This study aimed to assess the impact of mother/neonatal factors on the quality of CB units, collected for allogeneic transplantation. We analyzed 33 CB units collected in University Hospital of Obstetrics and Gynaecology "Maichin dom" and donated to the National public bank for stem cells, University Hospital "Alexandrovska", Sofia. A significant increase (p < 0.001) of total nucleated cell (TNC) values was found after CB processing. A trend of higher values of CD34+ cells was observed in CB units obtained from vaginal deliveries compared to Cesarian section births, and from female newborns compared to their male counterparts. CD34+ cell number positively correlated with CD34+ percentage and TNC count. Our preliminary data demonstrate the need of a large retrospective evaluation of different obstetric factors in order to establish criteria for appropriate selection in our country of umbilical cord blood donors for public banking. PMID:23234008

  6. Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients.

    PubMed

    Chilton, Paula M; Rezzoug, Francine; Ratajczak, Mariusz Z; Fugier-Vivier, Isabelle; Ratajczak, Janina; Kucia, Magda; Huang, Yiming; Tanner, Michael K; Ildstad, Suzanne T

    2005-03-01

    Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage-colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell-derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure. PMID:15522953

  7. Mechanisms of gravity-dependent changes in the bone tissue.

    PubMed

    Rodionova, N V; Oganov, V S; Polkovenko, O V

    2002-07-01

    The most typical changes for the bone under the space flight conditions and a long-term hypokinesia are the following: the decreasing in bone mass, the demineralization and a reducing of a mechanical strength. It can lead to osteopenia and osteoporosis development. Also it increases the risk of fractures of supporting bones. Osteopenies, caused by the microgravity, are partially connected with the increasing of a reduction of trabecular bones. [Cytological mechanisms of gravity-dependent reactions in a bone tissue remain in many respects not clear. The study purpose was the analysis of some ultrastructural changes in bone tissue cells of the monkeys (Macaca mulatta), staying during 2 weeks onboard the biosatellite "Bion-11".

  8. DEMINERALIZER BUILDING, TRA608. CAMERA IS ON RAW WATER TOWER AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DEMINERALIZER BUILDING, TRA-608. CAMERA IS ON RAW WATER TOWER AND FACES WEST. STEAM PLANT, TRA-609, AT UPPER EDGE OF VIEW. ABSENCE OF ROOF EXPOSES FIVE-BAY STRUCTURE AND INTERIOR DIVISION OF SPACE. CORRIDOR AT WEST END OF BUILDING WILL SEPARATE LABORATORY AND OFFICE SPACE FROM POTABLE WATER TANKS. ALONG NORTH WALL ARE SPACES FOR CATION AND ANION EXCHANGE UNITS. PENTHOUSE WILL ENCLOSE DEGASSIFIER. TANK AT LEFT (SOUTH) OF BUILDING STORES DEMINERALIZED WATER. NOTE BRINE STORAGE PIT, TRA-631, AT RIGHT OF VIEW, ABOVE PAIR OF CAUSTIC STORAGE TANKS. NOTE TRENCHES FOR BURIED WATER PIPES. INL NEGATIVE NO. 2732. Unknown Photographer, 6/29/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  9. Effects of fluoride on in vitro enamel demineralization analyzed by ¹⁹F MAS-NMR.

    PubMed

    Mohammed, N R; Kent, N W; Lynch, R J M; Karpukhina, N; Hill, R; Anderson, P

    2013-01-01

    The mechanistic action of fluoride on inhibition of enamel demineralization was investigated using (19)F magic angle spinning nuclear magnetic resonance (MAS-NMR). The aim of this study was to monitor the fluoride-mineral phase formed on the enamel as a function of the concentration of fluoride ions [F(-)] in the demineralizing medium. The secondary aim was to investigate fluorapatite formation on enamel in the mechanism of fluoride anti-caries efficacy. Enamel blocks were immersed into demineralization solutions of 0.1 M acetic acid (pH 4) with increasing concentrations of fluoride up to 2,262 ppm. At and below 45 ppm [F(-)] in the solution, (19)F MAS-NMR showed fluoride-substituted apatite formation, and above 45 ppm, calcium fluoride (CaF2) formed in increasing proportions. Further increases in [F(-)] caused no further reduction in demineralization, but increased the proportion of CaF2 formed. Additionally, the combined effect of strontium and fluoride on enamel demineralization was also investigated using (19)F MAS-NMR. The presence of 43 ppm [Sr(2+)] in addition to 45 ppm [F(-)] increases the fraction of fluoride-substituted apatite, but delays formation of CaF2 when compared to the demineralization of enamel in fluoride-only solution. PMID:23712030

  10. Effect of rotatory instrument speed on its capacity to remove demineralized and sound dentin

    PubMed Central

    Cortes, Mariana; Pecorari, Vanessa Galego Arias; Basting, Roberta Tarkany; França, Fabiana Mantovani Gomes; Turssi, Cecília Pedroso; do Amaral, Flávia Lucisano Botelho

    2013-01-01

    Objectives: The aim of this study was to evaluate the capacity of two rotatory instruments (controlled speed electric motor [CSEM] – 300 rpm; conventional slow handpiece [CSHP] – 18,000 rpm) to remove sound and demineralized dentin, by examining prepared cavity walls using the scanning electron microscopy (SEM) and assessing loss of mass. Materials and Methods: A total of 40 blocks of human occlusal dentin, measuring 5 mm × 5 mm × 4 mm (L × W × H), were divided into two groups according to the substrate type in which the cavity preparation was performed: D - demineralized dentin; and S - sound dentin (control group). The groups were subdivided according to the rotatory instrument used for cavity preparation (n = 10): CSEM (300 rpm); and CSHP (18,000 rpm). In half of the dentin blocks, caries lesion induction was performed for 6 weeks. The preparation of the cavities was performed on a standardizing machine, using a cylindrical tungsten carbide burr. Before and after the preparation, specimens were dehydrated in an incubator at 60°C for 30 min. The initial and final mass (in mg) of each dentin block was measured 3 times using the digital precision balance to obtain the mean weight Following cavity preparation, all specimens were hemisected and SEM was used to blindly assess each half so that the lateral walls of the prepared cavity were measured in μm, accepting the average of two measurements as the total depth of the preparation. Non-parametric Mann-Whitney analysis was performed with a 5% of significance level. Results: Regarding the weight difference (mg), no significance was detected between the groups. Regarding depth (μm), a significant difference was found between the groups, so that the CSRM showed lower cavity depth when compared with CSHP, both in sound and demineralized dentin. Conclusions: Controlled speed rotatory instruments were found to be more conservative in removing both sound and demineralized dentin, in terms of preparation and depth

  11. Microhardness of demineralized enamel following home bleaching and laser-assisted in office bleaching

    PubMed Central

    Ghanbarzadeh, Majid; Akbari, Majid; Hamzei, Haniye

    2015-01-01

    Background There is little data regarding the effect of tooth whitening on microhardness of white spot lesions. This study was conducted to investigate the effect of home-bleaching and laser-assisted in-office bleaching on microhardness of demineralized enamel. Material and Methods Forty bovine incisors were selected and immersed in a demineralizing solution for 12 weeks to induce white spot lesions. Enamel blocks were prepared and randomly assigned to two groups of 20 each. The first group underwent home bleaching with 15% carbamide peroxide which was applied for 8 hours a day over a period of 15 days. In the second group, in-office bleaching was performed by 40% hydrogen peroxide and powered by irradiation from an 810 nm gallium-aluminum-arsenide (GaAlAs) diode laser (CW, 2W). This process was performed for 3 sessions every seven days, in 15 days. The specimens were stored in Fusayama Meyer artificial saliva during the experiment. Surface microhardness was assessed before and after the bleaching therapies in both groups. Results Microhardness decreased significantly following both home bleaching and laser-assisted in-office bleaching (p<0.05). There were no significant differences in hardness values among the two groups either before (p=0.131) or after (p=0.182) the bleaching procedures. Conclusions Tooth whitening through home bleaching or laser-assisted in-office bleaching can result in a significant reduction in microhardness of white spot lesions. Therefore, it is suggested to take protective measures on bleached demineralized enamel. Key words:White spot lesion, bleaching, laser, microhardness, demineralized enamel, home bleaching, in-office bleaching. PMID:26330939

  12. Ability of Pit and Fissure Sealant-containing Amorphous Calcium Phosphate to inhibit Enamel Demineralization

    PubMed Central

    Owais, Arwa I; Kawaja, Wasan

    2016-01-01

    ABSTRACT Aim: To evaluate the effect of amorphous calcium phosphate (ACP)-containing pit and fissure sealant on inhibition of enamel demineralization in vitro. Materials and methods: Enamel specimens (n = 75) were prepared using freshly extracted noncarious human third molars. Box-shaped cavities (8 × 2 × 2 mm) on the buccal or lingual surfaces were prepared and restored with resin-based sealant (Concise™), ACP-containing sealant (Aegis®) or fluoride-containing sealant (Conseal-F™). The samples were acid challenged in a demineralizing solution of 50 mmol/l lactic acid at pH 5.0 for 4 days. The change in enamel microhardness (ASuH) was calculated. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey’s post hoc test. Results: The mean SuH0 (±SD) (in Vicker’s unit) prior to the acid challenge was: Concise™ (318.83 ± 33.86), Aegis® (331.03 ± 21.52), Conseal-F™ (310.12 ± 34.31). Following the acid challenge, the values dropped in all groups and ASuH (±SD) values were 269.17 ± 47.49, 151.39 ± 23.96 and 175.79 ± 32.39 respectively. Conclusion: The ACP-containing pit and fissure sealant has the potential to inhibit enamel demineralization. How to cite this article: Zawaideh FI, Owais AI, Kawaja W. Ability of pit and fissure sealant-containing amorphous calcium phosphate to inhibit enamel demineralization. Int J Clin Pediatr Dent 2016;9(1):10-14. PMID:27274148

  13. Morphological/Chemical Imaging of Demineralized Dentin Layer in Its Natural, Wet State

    PubMed Central

    Wang, Yong; Yao, Xiaomei

    2010-01-01

    Objective Measuring the structure, composition or suitability for bonding of the acid etched dentin substrate, especially in its hydrated state, has been a formidable problem. The purpose of this study was to determine the morphological and structural profiles of the dentin demineralized layer measured in its natural wet state using environmental scanning electron microscopy (ESEM) and micro-Raman imaging. Materials and methods The occlusal 1/3 of the crown was removed from 9 extracted, unerupted human third molars. Dentin surfaces were abraded with 600 grit SiC sandpaper under water to create smear layers. The prepared dentin surfaces were randomly selected for treatment with the self-etching agent (Adper™ Prompt L-Pop) or the total etching agent 35% H3PO4 gel (with/without agitation). Micro-Raman spectra and imaging were acquired at 1-1.5 μm spatial resolution at positions perpendicular to the treated surfaces; since this technique is non-destructive, the same specimens were also imaged with ESEM. Specimens were kept wet throughout spectral acquisition and ESEM observations. Results ESEM could be used to reveal demineralized layers in acid-etched dentin, but the resolution was low and no collagen fibrils were disclosed. The detailed chemical maps/profiles of demineralized dentin layers under wet conditions could be obtained using Raman imaging. It was shown that the mineral existed in the superficial layer of all etched dentin covered with smear layers. The mineral was much easier to be removed underneath the superficial layer. The depth, degree, and profile of dentin demineralization were dependent on the types of acids (self-etching vs. total etching) and application procedures (with vs. without agitation). Significance Most current adhesives are applied using wet bonding techniques in which the dentin is kept fully hydrated throughout the bonding. Our ability to fully characterize the hydrated, etched dentin substrates is very important for understanding

  14. Fluoride varnishes with calcium glycerophosphate: fluoride release and effect on in vitro enamel demineralization.

    PubMed

    Carvalho, Thiago Saads; Peters, Bianca Glerean; Rios, Daniela; Magalhães, Ana Carolina; Sampaio, Fabio Correia; Buzalaf, Marília Afonso Rabelo; Bönecker, Marcelo José Strazzeri

    2015-01-01

    The aims of this study were (1) to assess the amount of fluoride (F) released from varnishes containing calcium glycerophosphate (CaGP) and (2) to assess the effect of the experimental varnishes on in vitro demineralization. Six test groups using 5 varnishes: base varnish (no active ingredients); Duraphat® (2.26% NaF); Duofluorid® (5.63% NaF/CaF2); experimental varnish 1 (1% CaGP/5.63% NaF/CaF2); experimental varnish 2 (5% CaGP/5.63% NaF/CaF2); and no varnish were set up. In stage 1, 60 acrylic blocks were randomly distributed into 6 groups (n = 10). Then 300 µg of each varnish was applied to each block. The blocks were immersed in deionized water, which was changed after 1, 8, 12, 24, 48 and 72 hours. Fluoride concentration in the water was analyzed using a fluoride electrode. In stage 2, 60 bovine enamel samples were distributed into 6 groups (n = 10), and treated with 300 µg of the respective varnish. After 6 h the varnish was removed and the samples were subjected to a 7-day in vitro pH cycle (6 h demineralization/18 h remineralization per day). The demineralization was measured using surface hardness. The results showed that both experimental varnishes released more fluoride than Duofluorid® and Duraphat® (p < 0.05), but Duraphat® showed the best preventive effect by decreasing enamel hardness loss (p < 0.05). Therefore, we conclude that even though (1) the experimental varnishes containing CaGP released greater amounts of F, (2) they did not increase in the preventive effect against enamel demineralization. PMID:26176358

  15. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process

    PubMed Central

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix–only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications

  16. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process.

    PubMed

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix-only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications. PMID

  17. Effect of a new carbon dioxide laser and fluoride on sound and demineralized enamel

    NASA Astrophysics Data System (ADS)

    dos Santos, Marines N.; Featherstone, John D. B.; Fried, Daniel

    2001-04-01

    The present study aimed to test the hypothesis that irradiation of dental enamel by a TEA carbon dioxide laser together with fluoride, can effectively inhibit caries-like progression in sound and demineralized enamel. Blocks of human sound and demineralized dental enamel were divided into 11 treatment groups. Eighty enamel blocks were partially demineralized in a 50 percent HAP/0.1 M lactic acid/carbopol solution. Samples were treated with/without laser and/or F according to the above groups. The blocks were then submitted to 5 days of pH cycling. Microradiography was performed on 100 micrometers thin sections to determine the relative mineral loss as (Delta) Z and the percentage of caries inhibition for the laser and F treated groups. Mean (Delta) Z values for groups I-X were, respectively: 1043; 683; 614; 2294; 1803; 1708; 1547; 1791; 1656;; and 1385. The percent caries inhibition for groups II, III, V-X was respectively: 35, 41; 49; 62; 42; 53 and 76 percent. The combination of this new TEA CO2 laser and F treatment produced a significant protective effect against lesion progression.

  18. Enamel and dentine demineralization by a combination of starch and sucrose in a biofilm - caries model.

    PubMed

    Botelho, Juliana Nunes; Villegas-Salinas, Mario; Troncoso-Gajardo, Pía; Giacaman, Rodrigo Andrés; Cury, Jaime Aparecido

    2016-05-20

    Sucrose is the most cariogenic dietary carbohydrate and starch is considered non-cariogenic for enamel and moderately cariogenic for dentine. However, the cariogenicity of the combination of starch and sucrose remains unclear. The aim of this study was to evaluate the effect of this combination on Streptococcus mutans biofilm composition and enamel and dentine demineralization. Biofilms of S. mutans UA159 were grown on saliva-coated enamel and dentine slabs in culture medium containing 10% saliva. They were exposed (8 times/day) to one of the following treatments: 0.9% NaCl (negative control), 1% starch, 10% sucrose, or 1% starch and 10% sucrose (starch + sucrose). To simulate the effect of human salivary amylase on the starch metabolization, the biofilms were pretreated with saliva before each treatment and saliva was also added to the culture medium. Acidogenicity of the biofilm was estimated by evaluating (2 times/day) the culture medium pH. After 4 (dentine) or 5 (enamel) days of growth, biofilms (n = 9) were individually collected, and the biomass, viable microorganism count, and polysaccharide content were quantified. Dentine and enamel demineralization was assessed by determining the percentage of surface hardness loss. Biofilms exposed to starch + sucrose were more acidogenic and caused higher demineralization (p < 0.0001) on either enamel or dentine than those exposed to each carbohydrate alone. The findings suggest that starch increases the cariogenic potential of sucrose. PMID:27223133

  19. Natural and Controlled Demineralization for Study Purposes in Minimally Invasive Dentistry.

    PubMed

    Skucha-Nowak, Małgorzata; Gibas, Mirosław; Tanasiewicz, Marta; Twardawa, Henryk; Szklarski, Tomasz

    2015-01-01

    Artificially induced demineralization of enamel is frequently used during laboratory tests, particularly in minimally invasive dentistry. The aim of this study was to analyze demineralization techniques of hard tooth tissue applicable in the research of materials in minimally invasive dentistry. The most important factor taken into consideration when designing a method is to make a model as closely similar to the natural environment of the human oral cavity as it is possible. In vitro models allow us to maintain stability and control over the environment and guarantee repeatability of the results. There are main models to produce dental caries outside of the body. The first model is chemical and it uses acids. It is simplified and reflects the actual environment of the oral cavity to a lesser degree. The second model is biological and it is more accurate as it uses microorganisms which build the dental plaque. Among in vitro protocols are also used pH-cycling models. Based on the available literature, it was found that bovine teeth and human teeth with demineralization diagnosed while still inside the oral cavity are the most frequently used kind of specimens in research conducted with use of the chemical model. Not a single case of use of the biological and pH-cycling models were found in the available literature related to the research of infiltrants in minimally invasive dentistry.

  20. Natural and Controlled Demineralization for Study Purposes in Minimally Invasive Dentistry.

    PubMed

    Skucha-Nowak, Małgorzata; Gibas, Mirosław; Tanasiewicz, Marta; Twardawa, Henryk; Szklarski, Tomasz

    2015-01-01

    Artificially induced demineralization of enamel is frequently used during laboratory tests, particularly in minimally invasive dentistry. The aim of this study was to analyze demineralization techniques of hard tooth tissue applicable in the research of materials in minimally invasive dentistry. The most important factor taken into consideration when designing a method is to make a model as closely similar to the natural environment of the human oral cavity as it is possible. In vitro models allow us to maintain stability and control over the environment and guarantee repeatability of the results. There are main models to produce dental caries outside of the body. The first model is chemical and it uses acids. It is simplified and reflects the actual environment of the oral cavity to a lesser degree. The second model is biological and it is more accurate as it uses microorganisms which build the dental plaque. Among in vitro protocols are also used pH-cycling models. Based on the available literature, it was found that bovine teeth and human teeth with demineralization diagnosed while still inside the oral cavity are the most frequently used kind of specimens in research conducted with use of the chemical model. Not a single case of use of the biological and pH-cycling models were found in the available literature related to the research of infiltrants in minimally invasive dentistry. PMID:26768642

  1. EFFECT OF ADDING TRICALCIUM PHOSPHATE TO FLUORIDE MOUTHRINSE ON MICROHARDNESS OF DEMINERALIZED PRIMARY HUMAN TOOTH.

    PubMed

    Rirattanapong, Praphasri; Vongsavan, Kadkao; Saengsirinavin, Chavengkiat; Phuekcharoen, Pimonchat

    2015-05-01

    The purpose of the present study was to evaluate the effect of fluoride mouthrinse containing tricalcium phosphate on microhardness of demineralized primary enamel. Thirty-six sound primary incisors were immersed in a demineralizing solution (pH 4.4) for 96 hours at 37 degrees C to create artificial caries-like lesions. After artificial caries formation, the specimens were randomly divided into 3 groups (with 12 specimens in each group): Group A: deionized water; Group B: 0.05% NaF plus 20 ppm tricalcium phosphate mouthrinse and Group C: 0.05% NaF mouthrinse. All the specimens were immersed for 1 minute at 37 degrees C three times per day for 7 days in the respective mouthrinse among pH cycling. The surface microhardness was examined using a Vickers hardness tester (100 grams for 15 seconds) at baseline, before and after the pH-cycling procedure. Data were analyzed using one-way ANOVA and Tukey's multiple comparison tests with a significance level of 0.05. After treatment, Group Ahad a significantly lower surface microhardness value than the other two groups (p=0.000); however, there was no significant difference between Groups B and C (p=0.728). We concluded fluoride mouthrinse containing tricalcium phosphate and fluoride mouthrinse have similar remineralizing effects on microhardness of demineralized primary teeth. PMID:26521528

  2. Photon absorptiometry for non-invasive measurement of bone mineral content

    SciTech Connect

    Gupta, S.; Luna, E.; Belsky, J.; Gelfman, N.; Miller, K.; Davies, T.

    1984-08-01

    Bone mineral content of the distal radius was determined in 106 patients by single photon absorptiometry using iodine-125 monochromatic source. The technique provided a reliable means to assess the degree of mineral loss in conditions such as osteoporosis, renal osteodystrophy in patients on chronic maintenance dialysis, subjects on long-term steroid therapy, and those with diabetes mellitus. It is more sensitive than conventional radiography and completely noninvasive compared to bone biopsy. It is suggested that photon absorptiometry is a simple, sensitive, and reliable technique for assessment and follow-up of the bone mineral content in a host of disorders associated with bone demineralization.

  3. Specific allogeneic unresponsiveness in the adult host: present-day experimental models

    SciTech Connect

    Rapaport, F.T.; Bachvaroff, R.J.; Cronkite, E.; Chanana, A.; Sato, T.; Asari, H.; Waltzer, W.C.

    1982-01-01

    As part of a long-term intensive effort to apply the induction of adult allogensic unresponsiveness to the transplantation problem, two techniques to control the variability in the persistence of immunologically competent postthymic cells iin the treated host and/or the inoculum of autologous marrow returned to the host after irradiation are described. The first consisted of exposing the peripheral blood of prospective recipients to a 5-week course of extra-corporeal irradiation (ECIB), the other of exposing the stored autologous marrow scheduled to repopulate a given recipient to methyl-prednisolone (MPd) and DNase prior to renifusion into the recipient. Serial analysis of bone marrow cell samples at various intervals before and after treatment was undertaken. The significance of the disappearance of a particular population of nonnuclear cells from the samples, and the association of such disappearance with increased success in the induction of allogeneic unresponsiveness is discussed. (ACR)

  4. Bone density in limb-immobilized beagles: An animal model for bone loss in weightlessness

    NASA Technical Reports Server (NTRS)

    Wolinsky, Ira

    1987-01-01

    Prolonged weightlessness is man in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. In order to seek and test preventative measures an appropriate ground based animal model simulating weightlessness is necessary. Use of the mature Beagle in limb immobilization has been documented as an excellent model for orthopedic research since this animal most closely simulates the phenomenom of bone loss with regards to growth, remodeling, structure, chemistry and mineralization. The purpose of this project is to develop a research protocol for the study of bone loss in Beagles during and after cast immobilization of a hindleg; research will then be initiated.

  5. Relapse after allogeneic stem cell transplantation

    PubMed Central

    Barrett, A John; Battiwalla, Minoo

    2012-01-01

    Since allogeneic stem cell transplantation (SCT) represents an intensive curative treatment for high-risk malignancies, its failure to prevent relapse leaves few options for successful salvage treatment. While many patients have a high early mortality from relapse, some respond and have sustained remissions, and a minority has a second chance of cure with appropriate therapy. The prognosis for relapsed hematological malignancies after SCT depends on four factors: the time elapsed from SCT to relapse (with relapses occurring within 6 months having the worst prognosis), the disease type (with chronic leukemias and some lymphomas having a second possibility of cure with further treatment), the disease burden and site of relapse (with better treatment success if disease is treated early), and the conditions of the first transplant (with superior outcome for patients where there is an opportunity to increase either the alloimmune effect, the specificity of the antileukemia effect with targeted agents or the intensity of the conditioning in a second transplant). These features direct treatments toward either modified second transplants, chemotherapy, targeted antileukemia therapy, immunotherapy or palliative care. PMID:21083034

  6. Who is fit for allogeneic transplantation?

    PubMed Central

    Sandmaier, Brenda M.

    2010-01-01

    The use of allogeneic hematopoietic cell transplantation (HCT) has expanded progressively, facilitated by the increasing availability of unrelated donors and cord blood, and the inclusion of older patients as transplantation candidates. Indications remain diagnosis-dependent. As novel nontransplantation modalities have been developed concurrently, many patients come to HCT only when no longer responding to such therapy. However, patients with refractory or advanced disease frequently relapse after HCT, even with high-dose conditioning, and more so with reduced-intensity regimens as used for patients of older age or with comorbid conditions. Thus, patients with high-risk malignancies who have substantial comorbidities or are of advanced age are at high risk of both relapse and nonrelapse mortality and should probably not be transplanted. Being in remission or at least having shown responsiveness to pre-HCT therapy is generally associated with increased transplantation success. In addition, to handle the stress associated with HCT, patients need a good social support system and a secure financial net. They must be well informed, not only about the transplantation process, but also about expected or potential post-HCT events, including graft-versus-host disease and delayed effects that may become manifest only years after HCT. PMID:20702782

  7. Perfusion Method for Intra-bone Marrow Collection and Stem Cell Transplantation: A Critical Review.

    PubMed

    Korrapati, Narasimhulu; Nanganuru, Harikrishna Yadav

    2014-03-19

    A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Bone marrow is the soft, fatty tissue inside our bones. Bone marrow transplantation (BMT) is a powerful strategy for the treatment of leukemia, aplastic anemia, congenital immunodeficiency and autoimmune diseases. In humans, bone marrow cells (BMCs) have usually been collected by multiple bone marrow aspirations from the iliac crest. We have established a new "perfusion" method for collecting BMCs with minimal contamination with the peripheral blood using the long bones of cynomolgus monkeys. This method has proven to be a simple and safe method for harvesting BMCs and reduces the risk of acute graft versus host disease in allogeneic BMT. Intra-bone marrow-BMT (IBM-BMT) provides distinct advantages because it recruits donor-derived hematopoietic stem cells and mesenchymal stem cells. IBM-BMT has been shown to currently be the best strategy for allogeneic BMT. Here we review the perfusion method (for harvesting BMCs) and IBM-BMT (for their transplantation) and show that this combination will become a powerful new clinical strategy for allogeneic BMT.

  8. A bioresorbable polylactide implant used in bone cyst filling.

    PubMed

    Ficek, Krzysztof; Filipek, Jolanta; Wojciechowski, Piotr; Kopec, Konrad; Ewa, Stodolak-Zych; Blazewicz, Stanislaw

    2016-02-01

    The aims in treating patients diagnosed with critical-sized bone defects resulting from bone cysts are to replace the lost bone mass after its removal and to restore function. The standard treatment is autologous or allogeneic bone transplantation, notwithstanding the known consequences and risks due to possible bone infection, donor site morbidity, bleeding and nerve injury and possible undesirable immune reactions. Additionally, allogeneic grafts are inhomogeneous, with a mosaic of components with difficult-to-predict regenerative potential, because they consist of cancellous bone obtained from different bones from various cadavers. In the present study, a 22-year-old patient with a history of right humerus fracture due to bone cysts was diagnosed with recurrent cystic lesions based on X-ray results. The patient qualified for an experimental program, in which he was treated with the application of a bioresorbable polylactide hybrid sponge filled with autologous platelet-rich plasma. Computed tomography and magnetic resonance imaging performed 3, 6, and 36 months after surgery showed progressive ossification and bone formation inside the defect cavity in the humerus. Three years after treatment with the bone substitute, the patient is pain free, and the cystic lesions have not reoccurred.

  9. Bone Grafts

    MedlinePlus

    A bone graft transplants bone tissue. Surgeons use bone grafts to repair and rebuild diseased bones in your hips, knees, ... fractures or cancers. Once your body accepts the bone graft, it provides a framework for growth of new, ...

  10. Bone Diseases

    MedlinePlus

    ... avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bones can also ...

  11. Isolation, cultivation and characterisation of pigeon osteoblasts seeded on xenogeneic demineralised cancellous bone scaffold for bone grafting.

    PubMed

    Harvanová, Denisa; Hornák, Slavomír; Amrichová, Judita; Spaková, Tímea; Mikes, Jaromír; Plsíková, Jana; Ledecký, Valent; Rosocha, Ján

    2014-09-01

    Avian osteoblasts have been isolated particularly from chicken embryo, but data about other functional tissue sources of adult avian osteoblast precursors are missing. The method of preparation of pigeon osteoblasts is described in this study. We demonstrate that pigeon cancellous bone derived osteoblasts have particular proliferative capacity in vitro in comparison to mammalian species and developed endogenous ALP. Calcium deposits formation in vitro was confirmed by alizarin red staining. Only a few studies have attempted to investigate bone grafting and treatment of bone loss in birds. Lack of autologous bone grafts in birds has prompted investigation into the use of avian xenografts for bone augmentation. Here we present a method of xenografting of ostrich demineralised cancellous bone scaffold seeded with allogeneic adult pigeon osteoblasts. Ostrich demineralised cancellous bone scaffold supported proliferation of pigeon osteoblasts during two weeks of co - cultivation in vitro. Scanning electron microscopy demonstrated homogeneous adult pigeon osteoblasts attachment and distribution on the surface of xenogeneic ostrich demineralised cancellous bone. Our preliminary in vitro results indicate that demineralised cancellous bone from ostrich tibia could provide an effective biological support for growth and proliferation of allogeneic osteoblasts derived from cancellous bone of pigeons. PMID:24915787

  12. Isolation, cultivation and characterisation of pigeon osteoblasts seeded on xenogeneic demineralised cancellous bone scaffold for bone grafting.

    PubMed

    Harvanová, Denisa; Hornák, Slavomír; Amrichová, Judita; Spaková, Tímea; Mikes, Jaromír; Plsíková, Jana; Ledecký, Valent; Rosocha, Ján

    2014-09-01

    Avian osteoblasts have been isolated particularly from chicken embryo, but data about other functional tissue sources of adult avian osteoblast precursors are missing. The method of preparation of pigeon osteoblasts is described in this study. We demonstrate that pigeon cancellous bone derived osteoblasts have particular proliferative capacity in vitro in comparison to mammalian species and developed endogenous ALP. Calcium deposits formation in vitro was confirmed by alizarin red staining. Only a few studies have attempted to investigate bone grafting and treatment of bone loss in birds. Lack of autologous bone grafts in birds has prompted investigation into the use of avian xenografts for bone augmentation. Here we present a method of xenografting of ostrich demineralised cancellous bone scaffold seeded with allogeneic adult pigeon osteoblasts. Ostrich demineralised cancellous bone scaffold supported proliferation of pigeon osteoblasts during two weeks of co - cultivation in vitro. Scanning electron microscopy demonstrated homogeneous adult pigeon osteoblasts attachment and distribution on the surface of xenogeneic ostrich demineralised cancellous bone. Our preliminary in vitro results indicate that demineralised cancellous bone from ostrich tibia could provide an effective biological support for growth and proliferation of allogeneic osteoblasts derived from cancellous bone of pigeons.

  13. Hypercalcemia and altered biochemical bone markers in post-bone marrow transplantation osteopetrosis: a case report and literature review.

    PubMed

    Kulpiya, Alisa; Mahachoklertwattana, Pat; Pakakasama, Samart; Hongeng, Suradej; Poomthavorn, Preamrudee

    2012-08-01

    Autosomal recessive osteopetrosis is a rare disorder of bone resorption defect that results in generalized sclerotic bones and bone marrow failure. Allogeneic BMT is the only treatment for cure. One of the complications following a successful BMT is hypercalcemia that is a unique complication in this group of patients. We report a three-yr-old boy with osteopetrosis who developed hypercalcemia following the successful BMT. His maximal calcium level was 13.3 mg/dL. Markedly increased both bone formation and resorption markers were demonstrated along with hypercalcemia. These findings indicated an active donor-derived osteoclastic function and thus bone resorption following the successful donor engraftment in the patient. Treatment with hyperhydration, furosemide and bone resorption inhibitors, calcitonin, and bisphosphonate led to normalization of the serum calcium level. Bone resorption but not bone formation marker was persistently elevated despite having normocalcemia during a 16.5-month follow-up period.

  14. Weightlessness and bone loss in man

    NASA Technical Reports Server (NTRS)

    Rambaut, P. C.

    1983-01-01

    A review is presented of data whicih has been accumulated on the calcium and skeletal changes occurring in humans subjected to various periods of weightlessness. These data reveal that spaceflight induces an overall loss of calcium which continues unabated for at least three months. Urinary calcium levels reach a constant level within approximately four weeks while fecal calcium losses continue to increase throughout the flight period. A decline in the mineral density of weight-bearing bones accompanies these changes. Available data support the contention that the demineralization affects primarily the weight bearing bones. The rates of loss and recovery of calcium and bone mineral density are approximately equal to those observed during and following bedrest of comparable duration. No measure to wholly prevent these losses has yet been devised.

  15. Functional biomimetic analogs help remineralize apatite-depleted demineralized resin-infiltrated dentin via a bottom-up approach

    PubMed Central

    Kim, Jongryul; Arola, Dwayne D.; Gu, Lisha; Kim, Young Kyung; Mai, Sui; Liu, Yan; Pashley, David H.; Tay, Franklin R.

    2010-01-01

    Natural biominerals are formed through metastable amorphous precursor phases via a bottom-up, nanoparticle-mediated mineralization mechanism. Using an acid-etched human dentin model to create a layer of completely-demineralized collagen matrix, a bio-inspired mineralization scheme has been developed based on the use of dual biomimetic analogs. These analogs help to sequester fluidic amorphous calcium phosphate nanoprecursors and function as templates for guiding homogeneous apatite nucleation within the collagen fibrils. By adopting this scheme for remineralizing adhesive resin-bonded, completely-demineralized dentin, we have been able to redeposit intrafibrillar and extrafibrillar apatites in completely-demineralized collagen matrices that are imperfectly infiltrated by resins. This study utilizes a spectrum of completely- and partially-demineralized dentin collagen matrices to further validate the necessity for using a biomimetic analog-containing medium for remineralizing resin-infiltrated partially-demineralized collagen matrices in which remnant seed crystallites are present. In control specimens in which biomimetic analogs are absent from the remineralization medium, remineralization could only be seen in partially-demineralized collagen matrices probably by epitaxial growth via a top-down crystallization approach. Conversely, in the presence of biomimetic analogs in the remineralization medium, intrafibrillar remineralization of completely-demineralized collagen matrices via a bottom-up crystallization mechanism can additionally be identified. The latter is characterized by the transition of intrafibrillar minerals from an inchoate state of continuously-braided microfibrillar electron-dense amorphous strands to discrete nanocrystals, and ultimately into larger crystalline platelets within the collagen fibrils. Biomimetic remineralization via dual biomimetic analogs has the potential to be translated into a functional delivery system for salvaging failing

  16. A Critical Role for the TLR4/TRIF Pathway in Allogeneic Hematopoietic Cell Rejection by Innate Immune Cells

    PubMed Central

    Xu, Hong; Yan, Jun; Zhu, Ziqiang; Hussain, Lala-Rukh; Huang, Yiming; Ding, Chuanlin; Bozulic, Larry D.; Wen, Yujie; Ildstad, Suzanne T.

    2013-01-01

    We show for the first time that signaling through the TLR4/TRIF pathway plays a critical role in allogeneic bone marrow cell (BMC) rejection. This appears to be unique to BMC as organ allografts are rejected mainly via MyD88 signaling. Using T or T/B cell-deficient mice, we found that BMC allorejection occurred early before T cell activation and was T and B cell-independent, suggesting an effector role for innate immune cells in BMC rejection. We further demonstrated the innate immune signaling in BMC allorejection by showing superior engraftment in mice deficient in TRIF or TLR4 but not MyD88 or TLR3. The restored cytotoxicity in TRIF deficient recipients transferred with wildtype F4/80+ or NK1.1+ cells suggests TRIF signaling dependence on macrophages or NK cells in early BMC rejection. Production of the proinflammatory cytokine IL-6 and TRIF relevant chemokine MCP-1 was significantly increased early after bone marrow transplantation. In vivo specific depletion of macrophages or NK innate immune cells in combination with anti-CD154/rapamycin resulted in additive-enhanced allogeneic engraftment. The requirement for irradiation was completely eliminated when both macrophages and NK cells were depleted in combination with anti-CD154/rapamycin to target T and B cells, supporting the hypothesis that two barriers involving innate and adaptive immunity exist in mediating rejection of allogeneic BMC. In summary, our results clearly demonstrate a previously unappreciated role for innate immunity in BMC allorejection via signaling through a unique MyD88-independent TLR4/TRIF mechanism. These findings may have direct clinical impact on strategies for conditioning recipients for stem cell transplantation. PMID:23146386

  17. Cellular therapy following allogeneic stem-cell transplantation

    PubMed Central

    Rager, Alison

    2011-01-01

    Allogeneic hematopoietic stem-cell transplantation (HSCT) is the most effective approach for many patients with hematologic malignancies. Unfortunately, relapse remains the most common cause of death after allogeneic HSCT, and the prognosis of relapsed disease is poor for most patients. Induction of a graft-versus-leukemia (GVL), or graft-versus-tumor, effect through the use of donor leukocyte infusion (DLI), or donor lymphocyte infusion, has been remarkably successful for relapsed chronic myelogenous leukemia. Unfortunately, response to DLI in other hematologic malignancies is much less common and depends on many factors including histology, pace and extent of relapse, and time from HSCT to relapse. Furthermore, graft-versus-host disease (GVHD) is common after DLI and often limits successful immunotherapy. Ultimately, manipulations to minimize GVHD while preserving or enhancing GVL are necessary to improve outcomes for relapse after allogeneic HSCT. PMID:23556106

  18. Bone protein “extractomics”: comparing the efficiency of bone protein extractions of Gallus gallus in tandem mass spectrometry, with an eye towards paleoproteomics

    PubMed Central

    DeHart, Caroline J.; Schweitzer, Mary H.; Thomas, Paul M.; Kelleher, Neil L.

    2016-01-01

    Proteomic studies of bone require specialized extraction protocols to demineralize and solubilize proteins from within the bone matrix. Although various protocols exist for bone protein recovery, little is known about how discrete steps in each protocol affect the subset of the bone proteome recovered by mass spectrometry (MS) analyses. Characterizing these different “extractomes” will provide critical data for development of novel and more efficient protein extraction methodologies for fossils. Here, we analyze 22 unique sub-extractions of chicken bone and directly compare individual extraction components for their total protein yield and diversity and coverage of bone proteins identified by MS. We extracted proteins using different combinations and ratios of demineralizing reagents, protein-solubilizing reagents, and post-extraction buffer removal methods, then evaluated tryptic digests from 20 µg aliquots of each fraction by tandem MS/MS on a 12T FT-ICR mass spectrometer. We compared total numbers of peptide spectral matches, peptides, and proteins identified from each fraction, the redundancy of protein identifications between discrete steps of extraction methods, and the sequence coverage obtained for select, abundant proteins. Although both alpha chains of collagen I (the most abundant protein in bone) were found in all fractions, other collagenous and non-collagenous proteins (e.g., apolipoprotein, osteonectin, hemoglobin) were differentially identified. We found that when a standardized amount of extracted proteins was analyzed, extraction steps that yielded the most protein (by weight) from bone were often not the ones that produced the greatest diversity of bone proteins, or the highest degree of protein coverage. Generally, the highest degrees of diversity and coverage were obtained from demineralization fractions, and the proteins found in the subsequent solubilization fractions were highly redundant with those in the previous fraction. Based on

  19. Bone mineral measurement using dual energy x ray densitometry

    NASA Technical Reports Server (NTRS)

    Smith, Steven W.

    1989-01-01

    Bone mineral measurements before and after space missions have shown that weightlessness greatly accelerates bone demineralization. Bone mineral losses as high as 1 to 3 percent per month were reported. Highly precise instrumentation is required to monitor this loss and thereby test the efficacy of treatment. During the last year, a significant improvement was made in Dual-Photon Absorptiometry by replacing the radioactive source with an x ray tube. Advantages of this system include: better precision, lower patient dose, better spacial resolution, and shorter scan times. The high precision and low radiation dose of this technique will allow detection of bone mineral changes of less than 1 percent with measurements conducted directly at the sites of interest. This will allow the required bone mineral studies to be completed in a shorter time with greater confidence.

  20. Polychlorinated biphenyls (PCBs) depress allogeneic natural cytotoxicity by earthworm coelomocytes

    SciTech Connect

    Suzuki, M.M.; Cooper, E.L.; Eyambe, G.S.; Goven, A.J.; Fitzpatrick, L.C.; Venables, B.J. |

    1995-10-01

    Coelomocytes of the earthworm Lumbricus terrestris caused significant spontaneous allogeneic cytotoxicity in a 24-h trypan blue assay, but not in an assay using lactate dehydrogenase (LDH) release. Allogeneic cytotoxicity assays using cells from worms exposed to polychlorinated biphenyls (PCBs) suggest that PCBs can suppress a natural killing (NK-like) reaction. The implications of this work are twofold: understanding the evolution of natural killing (NK-like) activity and providing preliminary information on how spontaneous killing, a component of cellular immunity, may be compromised by pollutants.

  1. Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation.

    PubMed

    Ghavamzadeh, A; Alimoghadam, K; Nasseri, P; Jahani, M; Khodabandeh, A; Ghahremani, G

    1999-02-01

    Dyskeratosis congenita is recognized by its dermal lesions and constitutional aplastic anemia in some cases. We report successful allogeneic bone marrow transplantation in two siblings with this disease from their sister, and their long term follow-up. We used reduced doses of cyclophosphamide and busulfan for conditioning instead of total body irradiation. Also, we report late adverse effects of transplantation which are not distinguishable from the natural course of disease.

  2. Combining casein phosphopeptide-amorphous calcium phosphate with fluoride: synergistic remineralization potential of artificially demineralized enamel or not?

    NASA Astrophysics Data System (ADS)

    Elsayad, Iman; Sakr, Amal; Badr, Yahia

    2009-07-01

    Recaldent is a product of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP). The remineralizing potential of CPP-ACP per se, or when combined with 0.22% Fl gel on artificially demineralized enamel using laser florescence, is investigated. Mesial surfaces of 15 sound human molars are tested using a He-Cd laser beam at 441.5 nm with 18-mW power as an excitation source on a suitable setup based on a Spex 750-M monochromator provided with a photomultiplier tube (PMT) for detection of collected autofluorescence from sound enamel. Mesial surfaces are subjected to demineralization for ten days. The spectra from demineralized enamel are measured. Teeth are divided into three groups according to the remineralizing regimen: group 1 Recaldent per se, group 2 Recaldent combined with fluoride gel and ACP, and group 3 artificial saliva as a positive control. After following these protocols for three weeks, the spectra from the remineralized enamel are measured. The spectra of enamel autofluorescence are recorded and normalized to peak intensity at about 540 nm to compare spectra from sound, demineralized, and remineralized enamel surfaces. A slight red shift occurred in spectra from demineralized enamel, while a blue shift may occur in remineralized enamel. Group 2 shows the highest remineralizing potential. Combining fluoride and ACP with CPP-ACP can give a synergistic effect on enamel remineralization.

  3. Fluoride uptake and inhibition of intra-oral demineralization, following the application of varnishes with different concentrations of fluoride.

    PubMed

    de Bruyn, H; Buskes, J A; Jongebloed, W; Arends, J

    1988-06-01

    The relationship between the amount of fluoride acquired by human enamel after varnish application and the resulting inhibition demineralization of is presented and discussed. Intact human enamel was pretreated with Fluor Protector varnishes with differing fluoride contents (0.7; 0.1; 0.05 and 0 wt% F-) for 24 hours. In a first experiment the amount of fluoride acquired after application was determined. In a second experiment the pretreated enamel was stored intra-orally under constant plaque coverage, in order to create a substantial demineralization challenge. The protection against demineralization, induced by the various varnishes was determined four months after varnish application using microradiography. Under the cariogenic conditions created in this study, the fluoride containing varnishes induced a protection of 53-75%. Although the amount of fluoride uptake was strongly related to the fluoride content in the varnishes, no statistically significant difference in demineralization inhibition between the varnishes was observed. SEM investigation of the enamel lesions revealed globular precipitates inside the fluoridated enamel, presumably consisting of calcium fluoride-like material. The present study indicates that the fluoride content in Fluor Protector varnishes can be decreased without reducing its ability to inhibit demineralization.

  4. Multi-variety bone bank in China.

    PubMed

    Li, Dan; Bi, Long; Meng, Guo-Lin; Liu, Min; Jin, Jing; Liu, Yin; Wang, Zhen; Liu, Jian; Hu, Yun-Yu

    2010-08-01

    This is a descriptive report of the establishment and operation of a Chinese bone bank, though not a typical one. While being engaged in collection, processing and storage of allogeneic tissues, the bone bank to which the author belongs concurrently develops and produces new, non-human derived, graft materials. Among others is reconstituted bone xenograft (RBX) which possesses strong osteoinductive capability without evoking immune rejection. Hence, its appellation "multi-variety bone bank," which was established by Dr. Hu Yunyu in 1990, the first of its kind in China. There are several salient features discriminating this bone bank from others. At this hospital-based non-profit institution, allograft hemi-joints are freshly prepared and distributed deep-frozen, instead of being freeze-dried on an industrialized basis for convenient transportation. The former has much more superior biological and mechanical properties as compared with the latter. However, allogeneic tissues are sometimes in short supply due to limited number of donors and the risk of some potential donors carrying viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). New graft materials, including reconstituted bone xenograft (RBX), were developed that serve as a supplement to allografts. RBX has been successfully used in clinical practice for the management of old fractures, nonunions and bone defects, most notably of contaminated, infected open fractures and osteomyelitis with the use of anti-infective reconstituted bone xenograft (ARBX). Additionally the multi-variety bone bank serves as a training base for educating professional personnel and researchers (postgraduates) in theories and technologies of tissue banking. Up to now, eighteen special technical staff members and approximately sixty senior researchers have been trained at this institution.

  5. Effects of Treatment with Various Remineralizing Agents on the Microhardness of Demineralized Enamel Surface

    PubMed Central

    Salehzadeh Esfahani, Kiana; Mazaheri, Romina; Pishevar, Leila

    2015-01-01

    Background and aims. Remineralization of incipient caries is one of the goals in dental health care. The present study aimed at comparing the effects of casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP), Remin Pro®, and 5% sodium fluoride varnish on remineralization of enamel lesions. Materials and methods. In this in vitro study, 60 enamel samples were randomly allocated to six groups of 10. After four days of immersion in demineralizing solution, microhardness of all samples was measured. Afterward, groups 1-3 underwent one-time treatment with fluoride varnish, CPP-ACP, and Remin Pro®, respectively. Microhardness of groups 4-6 was measured not only after one-month treatment with the above-mentioned materials (for eight hours a day), but also after re-exposing to the demineralizing solution. The results were analyzed by one-way analysis of variance (ANOVA), repeated measures ANOVA, and Fisher’s least significant difference (LSD) test. Results. None of the regimens could increase microhardness in groups 1-3. However, one-month treatment regimens in groups 4-6 caused a significant increase in microhardness. The greatest microhardness was detected in the group treated with CPP-ACP (P = 0.001). In addition, although microhardness reduced following re-demineralization in all three groups, the mean reduction was minimum in the CPP-ACP-treated group (P < 0.001). Conclusion. While long-term repeated application of all compounds improved microhardness, the remineralization potential of CPP-ACP was significantly higher than that of Remin Pro® and sodium fluoride varnish. PMID:26889361

  6. Imaging Early Demineralization on Tooth Occlusal Surfaces with a High Definition InGaAs Camera

    PubMed Central

    Fried, William A.; Fried, Daniel; Chan, Kenneth H.; Darling, Cynthia L.

    2013-01-01

    In vivo and in vitro studies have shown that high contrast images of tooth demineralization can be acquired in the near-IR due to the high transparency of dental enamel. The purpose of this study is to compare the lesion contrast in reflectance at near-IR wavelengths coincident with high water absorption with those in the visible, the near-IR at 1300-nm and with fluorescence measurements for early lesions in occlusal surfaces. Twenty-four human molars were used in this in vitro study. Teeth were painted with an acid-resistant varnish, leaving a 4×4 mm window in the occlusal surface of each tooth exposed for demineralization. Artificial lesions were produced in the exposed windows after 1 & 2-day exposure to a demineralizing solution at pH 4.5. Lesions were imaged using NIR reflectance at 3 wavelengths, 1310, 1460 and 1600-nm using a high definition InGaAs camera. Visible light reflectance, and fluorescence with 405-nm excitation and detection at wavelengths greater than 500-nm were also used to acquire images for comparison. Crossed polarizers were used for reflectance measurements to reduce interference from specular reflectance. The contrast of both the 24 hr and 48 hr lesions were significantly higher (P<0.05) for NIR reflectance imaging at 1460-nm and 1600-nm than it was for NIR reflectance imaging at 1300-nm, visible reflectance imaging, and fluorescence. The results of this study suggest that NIR reflectance measurements at longer near-IR wavelengths coincident with higher water absorption are better suited for imaging early caries lesions. PMID:24357911

  7. Imaging early demineralization on tooth occlusional surfaces with a high definition InGaAs camera

    NASA Astrophysics Data System (ADS)

    Fried, William A.; Fried, Daniel; Chan, Kenneth H.; Darling, Cynthia L.

    In vivo and in vitro studies have shown that high contrast images of tooth demineralization can be acquired in the near-IR due to the high transparency of dental enamel. The purpose of this study is to compare the lesion contrast in reflectance at near-IR wavelengths coincident with high water absorption with those in the visible, the near-IR at 1300-nm and with fluorescence measurements for early lesions in occlusal surfaces. Twenty-four human molars were used in this in vitro study. Teeth were painted with an acidresistant varnish, leaving a 4×4 mm window in the occlusal surface of each tooth exposed for demineralization. Artificial lesions were produced in the exposed windows after 1 and 2-day exposure to a demineralizing solution at pH 4.5. Lesions were imaged using NIR reflectance at 3 wavelengths, 1310, 1460 and 1600-nm using a high definition InGaAs camera. Visible light reflectance, and fluorescence with 405-nm excitation and detection at wavelengths greater than 500-nm were also used to acquire images for comparison. Crossed polarizers were used for reflectance measurements to reduce interference from specular reflectance. The contrast of both the 24 hr and 48 hr lesions were significantly higher (P<0.05) for NIR reflectance imaging at 1460-nm and 1600-nm than it was for NIR reflectance imaging at 1300-nm, visible reflectance imaging, and fluorescence. The results of this study suggest that NIR reflectance measurements at longer near-IR wavelengths coincident with higher water absorption are better suited for imaging early caries lesions.

  8. Inhibition of enamel demineralization by buffering effect of S-PRG filler-containing dental sealant.

    PubMed

    Kaga, Masayuki; Kakuda, Shinichi; Ida, Yusuke; Toshima, Hirokazu; Hashimoto, Masanori; Endo, Kazuhiko; Sano, Hidehiko

    2014-02-01

    The buffering capacity and inhibitory effects on enamel demineralization of two commercially available dental sealants were evaluated in this study. The effects of filler particles were also examined. Disks of enamel and cured sealant materials of BeautiSealant (silica or S-PRG filler) or Teethmate F-1 were incubated in lactic acid solutions (pH 4.0) for 1-6 d. The pH changes and amounts of ions released in the solutions were assessed, and enamel surfaces were observed using a scanning electron microscope. The pH of the solution with BeautiSealant (S-PRG filler) was neutralized from pH 4.0 to pH 6.1 (after incubation for 1 d) and from pH 4.0 to pH 6.7 (after incubation for 6 d). In addition, no release of calcium ions was detected and the enamel surface was morphologically intact in scanning electron microscopy images. However, the pH of the solution with Teethmate F-1 remained below pH 4.0 during incubation from days 1 to 6. Calcium release was increased in solutions up to and after 6 d of incubation. Scanning electron microscopy images showed that the structures of hydroxyapatite rods were exposed at the specimen surfaces as a result of demineralization. Ions released from S-PRG filler-containing dental sealant rapidly buffered the lactic acid solution and inhibited enamel demineralization. PMID:24372898

  9. Combination effect of fluoride dentifrices and varnish on deciduous enamel demineralization.

    PubMed

    Gatti, Alessandra; Camargo, Lucila Basto; Imparato, José Carlos Pettorossi; Mendes, Fausto Medeiros; Raggio, Daniela Prócida

    2011-01-01

    The aim of this study was to evaluate the anticaries potential of 500 or 1100 ppm F dentifrices combined with fluoride varnish using a pH-cycling regimen. Seventy primary canines were covered with nail polish, leaving a 4×4 mm window on their buccal surface, and randomly assigned into 7 groups (n = 10): S: sound enamel not submitted to the pH-cycling regimen or treatment; N: negative control, submitted to the pH-cycling regimen without any treatment; D1 and D2: subjected to the pH-cycling regimen and treated twice daily with 1100 or 500 ppm F dentifrice, respectively; VF: fluoride varnish (subjected to F-varnish before and in the middle of the pH-cycling regimen); and VF+D1 and VF+D2. After 10 days, the teeth were sectioned, and enamel demineralization was assessed by cross-sectional hardness at different distances from the dental surface. Data were analyzed using a two-way ANOVA followed by Tukey's test. Dentifrice with 1100 ppm F and the combination of F-varnish with the dentifrices significantly reduced enamel demineralization compared with the negative control (p < 0.05), but the isolated effects of F-varnish and dentifrice with low concentration were not significant (p > 0.05). The effect of combining F-varnish with the dentifrices was not greater than the effect of the dentifrices alone (p < 0.05). The data suggest that the combination of F-varnish with dentifrices containing 500 and 1100 ppm F is not more effective in reducing demineralization in primary teeth than the isolated effect of dentifrice containing 1100 ppm F. PMID:22031057

  10. Effects of Treatment with Various Remineralizing Agents on the Microhardness of Demineralized Enamel Surface.

    PubMed

    Salehzadeh Esfahani, Kiana; Mazaheri, Romina; Pishevar, Leila

    2015-01-01

    Background and aims. Remineralization of incipient caries is one of the goals in dental health care. The present study aimed at comparing the effects of casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP), Remin Pro(®), and 5% sodium fluoride varnish on remineralization of enamel lesions. Materials and methods. In this in vitro study, 60 enamel samples were randomly allocated to six groups of 10. After four days of immersion in demineralizing solution, microhardness of all samples was measured. Afterward, groups 1-3 underwent one-time treatment with fluoride varnish, CPP-ACP, and Remin Pro(®), respectively. Microhardness of groups 4-6 was measured not only after one-month treatment with the above-mentioned materials (for eight hours a day), but also after re-exposing to the demineralizing solution. The results were analyzed by one-way analysis of variance (ANOVA), repeated measures ANOVA, and Fisher's least significant difference (LSD) test. Results . None of the regimens could increase microhardness in groups 1-3. However, one-month treatment regimens in groups 4-6 caused a significant increase in microhardness. The greatest microhardness was detected in the group treated with CPP-ACP (P = 0.001). In addition, although microhardness reduced following re-demineralization in all three groups, the mean reduction was minimum in the CPP-ACP-treated group (P < 0.001). Conclusion. While long-term repeated application of all compounds improved microhardness, the remineralization potential of CPP-ACP was significantly higher than that of Remin Pro(®) and sodium fluoride varnish. PMID:26889361

  11. Photoacoustic and ultrasound characterization of bone composition

    NASA Astrophysics Data System (ADS)

    Lashkari, Bahman; Yang, Lifeng; Liu, Lixian; Tan, Joel W. Y.; Mandelis, Andreas

    2015-02-01

    This study examines the sensitivity and specificity of backscattered ultrasound (US) and backscattering photoacoustic (PA) signals for bone composition variation assessment. The conventional approach in the evaluation of bone health relies on measurement of bone mineral density (BMD). Although, a crucial and probably the most important parameter, BMD is not the only factor defining the bone health. New trends in osteoporosis research, also pursue the changes in collagen content and cross-links with bone diseases and aging. Therefore, any non-invasive method that can assess any of these parameters can improve the diagnostic tools and also can help with the biomedical studies on the diseases themselves. Our previous studies show that both US and PA are responsive to changes in the BMD, PA is, in addition, sensitive to changes in the collagen content of the bone. Measurements were performed on bone samples before and after mild demineralization and decollagenization at the exact same points. Results show that combining both modalities can enhance the sensitivity and specificity of diagnostic tool.

  12. Preparation of porous PLA/DBM composite biomaterials and experimental research of repair rabbit radius segmental bone defect.

    PubMed

    Zhang, Yumin; Wang, Jianru; Wang, Jue; Niu, Xiaojun; Liu, Jianchun; Gao, Lan; Zhai, Xiaoyan; Chu, Kaibo

    2015-12-01

    Bone substitutes are used in wide range of orthopaedic application. An ideal bone substitute should exhibit superior osteoinductive and osteoconductive properties. Neither bio-derived materials nor synthetic materials can meet the needs of an ideal bone substitute. Preparation of composite materials is a promising way to improve properties of biomaterial. In this study, the porous poly lactic acid (PLA)/demineralized bone matrix (DBM) composite biomaterials prepared by supercritical CO2 technique were implanted to repair rabbit radius segmental bone defect. By comparing with PLA and bone autograft, the X-ray result and histological analysis showed the repair effect of PLA/DBM porous composite materials is significantly better than that of the PLA group and the blank control group, and is similar to autologous bone. The PLA/DBM can promote the healing of bone defects and can be used as a kind of ideal alternative materials to repair bone defects.

  13. Preparation of porous PLA/DBM composite biomaterials and experimental research of repair rabbit radius segmental bone defect.

    PubMed

    Zhang, Yumin; Wang, Jianru; Wang, Jue; Niu, Xiaojun; Liu, Jianchun; Gao, Lan; Zhai, Xiaoyan; Chu, Kaibo

    2015-12-01

    Bone substitutes are used in wide range of orthopaedic application. An ideal bone substitute should exhibit superior osteoinductive and osteoconductive properties. Neither bio-derived materials nor synthetic materials can meet the needs of an ideal bone substitute. Preparation of composite materials is a promising way to improve properties of biomaterial. In this study, the porous poly lactic acid (PLA)/demineralized bone matrix (DBM) composite biomaterials prepared by supercritical CO2 technique were implanted to repair rabbit radius segmental bone defect. By comparing with PLA and bone autograft, the X-ray result and histological analysis showed the repair effect of PLA/DBM porous composite materials is significantly better than that of the PLA group and the blank control group, and is similar to autologous bone. The PLA/DBM can promote the healing of bone defects and can be used as a kind of ideal alternative materials to repair bone defects. PMID:25904497

  14. Tetracycline demineralization of dentin: the effects of concentration and application time.

    PubMed

    Sterrett, J D; Simmons, J; Whitford, G; Russell, C M

    1997-07-01

    The current investigation was initiated to study the effect concentration and application time has on the rate of tetracycline demineralization of dentin. Buccal and lingual surfaces of extracted bovine molars were ground to a smooth flat dentin surface using wetted silicon carbide discs. Standardized depressions were made in the dentin surface with a #909-055 diamond round wheel. Fresh tetracycline HCl (TTC-HCl) (Flavine Int. Inc.) solutions, i.e., 0, 25, 50, 75, 100, 125 and 150 mg/ml were prepared. A 30% citric acid solution was used as a positive control. The pH of each solution was recorded. 7 microl of each solution were pipetted into a depression and remained undisturbed for 1, 3, or 5 min. At the end of each application time period a fresh #3 cotton pellet was placed in the depression, once every 20 s for 1 min, to soak up the solution. The 3 pellets were placed in a 2.00 ml of 18 M omega H2O sample. As a measure of the rate of demineralization, the parts per million calcium (ppm Ca++) found in each sample were determined using atomic absorption spectrophotometry. Two-way analysis of variance was used to determine effects of TTC-HCI concentration and time on the rate of demineralization. No significant differences were found in the mean ppm Ca++ released at 1-, 3- and 5-min application times for 0, 25, or 50 mg/ml TTC. No significant differences were found in the mean ppm Ca++ released (i) between 3- and 5-min application times for 75, 100, 125 and 150 mg/ml TTC-HCl solutions and (ii) between 75, 100, 125 and 150 mg/ml TTC-HCl solutions within either the 3- or 5-min application times. The mean ppm Ca++ released at 3- and 5-min application times for 75, 100, 125 and 150 mg/ml TTC-HCI solutions were all significantly greater than the respective readings at the 1-min application time. The mean ppm Ca++ recorded for the 30% citric acid solution for all 3 application times were 3 to 5.5 x greater than the highest mean ppm Ca++ recording for TTC-HCl. The results

  15. Actinomycosis after allogeneic hematopoietic stem cell transplantation despite penicillin prophylaxis.

    PubMed

    Barraco, F; Labussière-Wallet, H; Valour, F; Ducastelle-Leprêtre, S; Nicolini, F-E; Thomas, X; Ferry, T; Dumitrescu, O; Michallet, M; Ader, F

    2016-08-01

    Actinomycosis is a rare chronic and multifaceted disease caused by Actinomyces species frequently mimicking malignancy or other chronic granulomatous lung diseases. We report 4 original presentations of actinomycosis arising under supposed penicillin prophylaxis in allogeneic stem cell transplantation recipients. PMID:27203624

  16. Cell salvage for minimising perioperative allogeneic blood transfusion

    PubMed Central

    Carless, Paul A; Henry, David A; Moxey, Annette J; O’Connell, Dianne; Brown, Tamara; Fergusson, Dean A

    2014-01-01

    Background Concerns regarding the safety of transfused blood have prompted reconsideration of the use of allogeneic (from an unrelated donor) red blood cell (RBC) transfusion, and a range of techniques to minimise transfusion requirements. Objectives To examine the evidence for the efficacy of cell salvage in reducing allogeneic blood transfusion and the evidence for any effect on clinical outcomes. Search methods We identified studies by searching CENTRAL (The Cochrane Library 2009, Issue 2), MEDLINE (1950 to June 2009), EMBASE (1980 to June 2009), the internet (to August 2009) and bibliographies of published articles. Selection criteria Randomised controlled trials with a concurrent control group in which adult patients, scheduled for non-urgent surgery, were randomised to cell salvage (autotransfusion) or to a control group who did not receive the intervention. Data collection and analysis Data were independently extracted and the risk of bias assessed. Relative risks (RR) and weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Data were pooled using a random-effects model. The primary outcomes were the number of patients exposed to allogeneic red cell transfusion and the amount of blood transfused. Other clinical outcomes are detailed in the review. Main results A total of 75 trials were included. Overall, the use of cell salvage reduced the rate of exposure to allogeneic RBC transfusion by a relative 38% (RR 0.62; 95% CI 0.55 to 0.70). The absolute reduction in risk (ARR) of receiving an allogeneic RBC transfusion was 21% (95% CI 15% to 26%). In orthopaedic procedures the RR of exposure to RBC transfusion was 0.46 (95% CI 0.37 to 0.57) compared to 0.77 (95% CI 0.69 to 0.86) for cardiac procedures. The use of cell salvage resulted in an average saving of 0.68 units of allogeneic RBC per patient (WMD −0.68; 95% CI −0.88 to −0.49). Cell salvage did not appear to impact adversely on clinical outcomes. Authors’ conclusions

  17. Nondestructive assessment of dentin demineralization using polarization sensitive optical coherence tomography after exposure to fluoride and laser irradiation

    PubMed Central

    Manesh, Saman K.; Darling, Cynthia L.; Fried, Daniel

    2009-01-01

    Previous studies have demonstrated that polarization sensitive optical coherence tomography (PS-OCT) can be used to image natural and artificial caries in dentin. The purpose of this study was to measure non-destructively the severity of artificial caries lesions in dentin and determine the efficacy of intervention with anti-caries agents including fluoride and lasers. Although several studies have assessed the utility of PS-OCT to image caries lesions in enamel and to quantify the lesion severity, only a few studies have focused on lesions in dentin. In this study images of artificial dentin lesions on extracted human teeth were acquired with PS-OCT. Before exposure to an artificial demineralizing solution, three incisions were made on the sample surfaces using either Er:YAG, Nd:YAG (λ=355-nm), or TEA CO2 lasers and selected areas were treated with topical fluoride to create six unique treatment areas for each of the three laser conditions investigated. The integrated reflectivity and depth of demineralization were calculated for each of the six areas on each sample using the PS-OCT images. Polarized light microscopy (PLM) and transverse microradiography (TMR) were used to measure lesion severity on histological thin sections for comparison. PS-OCT successfully measured the inhibition of demineralization by topical fluoride. Laser irradiation was not particularly effective in increasing or decreasing the rate of dentin demineralization. PLM and TMR corroborated those results. This study demonstrates that PS-OCT can be used to measure demineralization on dentin surfaces and determine the degree of inhibition of demineralization by anti-caries agents. PMID:19283826

  18. Prolonged bone marrow and skin allograft survival after pretransplant conditioning with cyclophosphamide and total lymphoid irradiation. [Mice

    SciTech Connect

    Kersey, J.H.; Kruger, J.; Song, C.; Kloster, B.

    1980-05-01

    Current studies were designed to provide long-term survival of allogeneic skin and bone marrow in mice preconditioned with various combinations of cyclophosphamide (CY) and/or total lymphoid irradiation (TLI). Long-term skin graft and bone marrow survival was obtained across the major histocompatibility barrier (BALB/c into C57BL/6) using pregrafting conditioning with either fractionated TLI or the combination of CY with a single dose of TLI. CY alone and a single dose of TLI alone were relatively ineffective as regrafting immunosuppressive combinations. Allogeneic bone marrow was required for long-term skin graft survival with either conditioning regimen. Allogeneic marrow transplantation resulted in somewhat more deaths than syngeneic transplantation with both CY + TLI and fractionated TLI.

  19. Nutritional status of patients submitted to transplantation of allogeneic hematopoietic stem cells: a retrospective study

    PubMed Central

    Ferreira, Érika Elias; Guerra, Daiane Cristina; Baluz, Kátia; de Resende Furtado, Wander; da Silva Bouzas, Luis Fernando

    2014-01-01

    Objective This study aimed to describe and compare the nutritional status of adult patients submitted to allogeneic hematopoietic stem cell transplantation at two different time points (admission and discharge). Methods A retrospective, descriptive and quantitative study was performed based on clinical, laboratory and nutritional data obtained from medical records of adult patients of both genders submitted to allogeneic hematopoietic stem cell transplantation in a bone marrow transplantation reference center in Rio de Janeiro in the period from 2010 to 2013. Statistical analysis was performed using the SPSS software (version 22.0). Results Sixty-four patients were evaluated. The mean age was 42.1 ± 3.2 years and the most prevalent disease was acute myeloid leukemia (39%). There was a high prevalence of gastrointestinal symptoms including nausea (100%), vomiting (97%) and mucositis (93%). Between admission and discharge there was a significant decrease in the median weight (−2.5 kg; 71.5 vs. 68.75 kg; p-value < 0.001), body mass index (−0.9 kg/m2; 24.8 vs. 24.4 kg/m2; p-value < 0.001), and serum albumin levels (−0.2 g/dL; 3.7 vs. 3.6 g/dL; p-value = 0.024). The survival time after hematopoietic stem cell transplantation correlated negatively with C-reactive protein at discharge (CC = −0.72; p-value < 0.001) and positively with serum albumin levels (CC = 0.56; p-value = 0.004) and with high total protein level at discharge (CC = 0.53; p-value = 0.006). Conclusion Our results suggest that patients submitted to allogeneic hematopoietic stem cell transplantation have compromised nutritional status during the hospital stay for transplantation. PMID:25453651

  20. Concentrations and antioxidative activity of anserine and carnosine in poultry meat extracts treated with demineralization and papain.

    PubMed

    Huang, S C; Kuo, J C

    2000-10-01

    Anserine and carnosine found in animal skeletal muscle are capable of inhibiting the catalysis of lipid oxidation by heme and non-heme iron. A demineralization technique and a proteolytic enzyme (papain) were used in this research in order to reduce the levels of proxidants while maintaining high levels of anserine and camosine in poultry (chicken, duck and turkey) meat extracts. Undemineralized poultry meat extracts contained larger amounts of anserine, camosine, heme and non-heme iron (p < 0.05) than did demineralized poultry meat extracts. Both undemineralized and demineralized breast meat extracts of chicken, duck and turkey contained higher concentrations of anserine and camosine, but lower amounts of heme and non-heme iron than did thigh meat extracts. In chicken, duck and turkey meat (breast and thigh) extracts (undemineralized and demineralized), the anserine concentrations were greater (p < 0.05) than the camosine concentrations. The hydrogen-donating ability of undemineralized and demineralized chicken breast meat extracts was not significantly different (p > 0.05): however, demineralized chicken breast meat extracts showed higher (p < 0.05) ferrous chelating ability than did undemineralized meat extracts. The concentrations of anserine, camosine, heme and non-heme iron in chicken breast meat extracts increased (p < 0.05) with the addition of papain (1%) to the meat mixture before extraction. Heme and non-heme iron in the chicken breast meat extracts increased as the reaction time for papain increased from 30 to 120 min, but the concentrations of anserine and camosine were not significantly affected by the longer reaction time for papain. The hydrogen-donating ability and ferrous chelating ability of demineralized chicken breast meat extracts were not significantly affected by papain. The ratios of carnosine/anserine were very specific in the chicken, duck and turkey meat extracts (breast and thigh); and the turkey meat extracts had lower (p < 0

  1. Extraction of high value added gelatin biopolymer from black tilapia (Oreochromis mossambicus) head bones

    NASA Astrophysics Data System (ADS)

    Sockalingam, K.; Abdullah, H. Z.

    2015-07-01

    Black tilapia (Oreochromis mossambicus) fish head bones were evaluated for its possibilities in extracting gelatin. Head bones were subjected to pre-treatment with 3% of hydrochloric acid (HCl) for demineralization before undergoes thermal extraction process. The raw head bones were characterized via Scanning Electron Microscopy (SEM) in order to investigate the external and internal surface morphology. SEM images also reveal the presence of collagen fiber with 1 µm diameter in the head bone. The black tilapia fish head bones yields 5.75 % of gelatin in wet weight basis, indicating the possibility of this fish species as sources of gelatin. Further characterizations were done on both raw head bones and extracted gelatin through Fourier Transform Infrared Spectroscopy (FTIR) and proximate analysis. The head bones gelatin shows high protein (10.55%) and ash (3.11 %) content with low moisture. This further proves the effectiveness of demineralization and extraction method used. The black tilapia fish head bones are found to be a prospective source of gelatin with good chemical and functional properties.

  2. Extraction of high value added gelatin biopolymer from black tilapia (Oreochromis mossambicus) head bones

    SciTech Connect

    Sockalingam, K. Abdullah, H. Z.

    2015-07-22

    Black tilapia (Oreochromis mossambicus) fish head bones were evaluated for its possibilities in extracting gelatin. Head bones were subjected to pre-treatment with 3% of hydrochloric acid (HCl) for demineralization before undergoes thermal extraction process. The raw head bones were characterized via Scanning Electron Microscopy (SEM) in order to investigate the external and internal surface morphology. SEM images also reveal the presence of collagen fiber with 1 µm diameter in the head bone. The black tilapia fish head bones yields 5.75 % of gelatin in wet weight basis, indicating the possibility of this fish species as sources of gelatin. Further characterizations were done on both raw head bones and extracted gelatin through Fourier Transform Infrared Spectroscopy (FTIR) and proximate analysis. The head bones gelatin shows high protein (10.55%) and ash (3.11 %) content with low moisture. This further proves the effectiveness of demineralization and extraction method used. The black tilapia fish head bones are found to be a prospective source of gelatin with good chemical and functional properties.

  3. Primary Graft Failure after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

    PubMed Central

    Olsson, Richard F.; Logan, Brent R.; Chaudhury, Sonali; Zhu, Xiaochun; Akpek, Görgün; Bolwell, Brian J.; Bredeson, Christopher N.; Dvorak, Christopher C.; Gupta, Vikas; Ho, Vincent T.; Lazarus, Hillard M.; Marks, David I.; Ringdén, Olle T.H.; Pasquini, Marcelo C.; Schriber, Jeffrey R.; Cooke, Kenneth R.

    2015-01-01

    Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1,278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared to bone marrow grafts (2.5 vs. 7.3%; P<0.001). A 4-fold increase of PGF was observed in myeloproliferative disorders compared to acute leukemia (P<0.001). Other risk factors for PGF included recipient age below 30, HLA-mismatch, male recipients of female donor grafts, ABO-incompatibility, busulfan/cyclophosphamide conditioning, and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 108/kg were associated with PGF (OR 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post-transplant may provide the rationale for an early request for additional hematopoietic stem cells. PMID:25772027

  4. Management of endocrino-metabolic dysfunctions after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Vantyghem, Marie-Christine; Cornillon, Jérôme; Decanter, Christine; Defrance, Frédérique; Karrouz, Wassila; Leroy, Clara; Le Mapihan, Kristell; Couturier, Marie-Anne; De Berranger, Eva; Hermet, Eric; Maillard, Natacha; Marcais, Ambroise; Francois, Sylvie; Tabrizi, Reza; Yakoub-Agha, Ibrahim

    2014-10-29

    Allogeneic hematopoietic stem cell transplantation is mainly indicated in bone marrow dysfunction related to blood diseases, but also in some rare diseases (adrenoleucodystrophy, mitochondrial neurogastrointestinal encephalomyopathy or MNGIE...). After decades, this treatment has proven to be efficient at the cost of numerous early and delayed side effects such as infection, graft-versus-host disease, cardiovascular complications and secondary malignancies. These complications are mainly related to the conditioning, which requires a powerful chemotherapy associated to total body irradiation (myelo-ablation) or immunosuppression (non myelo-ablation). Among side effects, the endocrine complications may be classified as 1) hormonal endocrine deficiencies (particularly gonado- and somatotropic) related to delayed consequences of chemo- and above all radiotherapy, with their consequences on growth, puberty, bone and fertility); 2) auto-immune diseases, particularly dysthyroidism; 3) secondary tumors involving either endocrine glands (thyroid carcinoma) or dependent on hormonal status (breast cancer, meningioma), favored by immune dysregulation and radiotherapy; 4) metabolic complications, especially steroid-induced diabetes and dyslipidemia with their increased cardio-vascular risk. These complications are intricate. Moreover, hormone replacement therapy can modulate the cardio-vascular or the tumoral risk of patients, already increased by radiotherapy and chemotherapy, especially steroids and anthracyclins... Therefore, patients and families should be informed of these side effects and of the importance of a long-term follow-up requiring a multidisciplinary approach.

  5. Electron probe micro-analysis for subsurface demineralization and remineralization of dental enamel

    SciTech Connect

    Chu, J.S.; Fox, J.L.; Higuchi, W.I.; Nash, W.P.

    1989-01-01

    A quantitative study of fluoride distribution profile changes in dental enamel was conducted by means of electron probe micro-analysis (EPMA). Fluoride-deposited hydroxyapatite powders were chosen as fluoride standards, and analytical conditions were optimized. The lower limit of detection for fluoride was estimated to be 270 ppm, with an accelerating voltage of 5 kV, a specimen current of 40 nA, and a counting time of 40 seconds. Fluoride profiles in fluoride-treated dental enamel, which exhibited intact surface layers and subsurface demineralization, were determined. The results were also compared with those of an acid-abrasion method, and reasonable consistency was found between these two methods, although the acid-abrasion procedure yielded a slightly lower fluoride content in the initial layers, followed by a higher content of fluoride in the deeper layers. The precision of fluoride profile data obtained from EPMA permits further studies to be conducted on the kinetics of subsurface demineralization and intact surface layer formation (white spot formation) which is observed during the acid challenge of dental enamel.

  6. Enamel resistance to demineralization following Er:YAG laser etching for bonding orthodontic brackets

    PubMed Central

    Ahrari, Farzaneh; Poosti, Maryam; Motahari, Pourya

    2012-01-01

    Background: Several studies have shown that laser-etching of enamel for bonding orthodontic brackets could be an appropriate alternative for acid conditioning, since a potential advantage of laser could or might be caries prevention. This study compared enamel resistance to demineralization following etching with acid phosphoric or Er:YAG laser for bonding orthodontic brackets. Materials and Methods: Fifty sound human premolars were divided into two equal groups. In the first group, enamel was etched with 37% phosphoric acid for 15 seconds. In the second group, Er:YAG laser (wavelength, 2 940 nm; 300 mJ/pulse, 10 pulses per second, 10 seconds) was used for tooth conditioning. The teeth were subjected to 4-day PH-cycling process to induce caries-like lesions. The teeth were then sectioned and the surface area of the lesion was calculated in each microphotographs and expressed in pixel. The total surface of each specimen was 196 608 pixels. Results: Mean lesion areas were 7 171 and 7532 pixels for Laser-etched and Acid-etched groups, respectively. The two sample t-test showed that there was no significant difference in lesion area between the two groups (P = 0.914). Conclusion: Although Er:YAG laser seems promising for etching enamel before bonding orthodontic brackets, it does not reduce enamel demineralization when exposed to acid challenge. PMID:23162591

  7. Selective removal of demineralization using near infrared cross polarization reflectance and a carbon dioxide laser

    NASA Astrophysics Data System (ADS)

    Chan, Kenneth H.; Fried, Daniel

    2012-01-01

    Lasers can ablate/remove tissue in a non-contact mode of operation and a pulsed laser beam does not interfere with the ability to image the tooth surface, therefore lasers are ideally suited for integration with imaging devices for image-guided ablation. Laser energy can be rapidly and efficiently delivered to tooth surfaces using a digitally controlled laser beam scanning system for precise and selective laser ablation with minimal loss of healthy tissues. Under the appropriate irradiation conditions such laser energy can induce beneficial chemical and morphological changes in the walls of the drilled cavity that can increase resistance to further dental decay and produce surfaces with enhanced adhesive properties to restorative materials. Previous studies have shown that images acquired using near-IR transillumination, optical coherence tomography and fluorescence can be used to guide the laser for selective removal of demineralized enamel. Recent studies have shown that NIR reflectance measurements at 1470-nm can be used to obtain images of enamel demineralization with very high contrast. The purpose of this study was to demonstrate that image guided ablation of occlusal lesions can be successfully carried out using a NIR reflectance imaging system coupled with a carbon dioxide laser operating at 9.3-μm with high pulse repetition rates.

  8. Orthodontic Cements and Demineralization: An In Vitro Comparative Scanning Electron Microscope Study

    PubMed Central

    Prabhavathi, V; Jacob, Josy; Kiran, M Shashi; Ramakrishnan, Murugesan; Sethi, Esha; Krishnan, C S

    2015-01-01

    Background: Comparison of the demineralization potential of four luting cements, i.e. zinc phosphate, conventional glass ionomer cement (GIC), resin-modified GIC and acid modified composite resin. Materials and Methods: This study was conducted on 75 extracted premolar teeth, which were grouped into five, each group containing 15 teeth. Groups were non-banded control, teeth cemented with the above-mentioned cements. These were incubated at 37°C for 30 days in sealable plastic containers, after which the teeth were debanded, cleaned and placed in acid gelatin solution at 37°C for 4 weeks to simulate the cariogenic solution. Then, the teeth were sectioned and examined under scanning electron microscope. The depth of the carious lesions was measured using image analysis with Digimizer software. Results: The depth of the carious lesions was maximum with non-banded group, followed by zinc phosphate, acid modified composite resin, resin-modified GIC and conventional GIC. Conclusions: Among the four orthodontic banding cements compared, the enamel demineralization potential is least with conventional GIC, followed by resin-modified GIC, acid modified composite resin and zinc phosphate. PMID:25859103

  9. Cryopreserved Ex Vivo-Expanded Allogeneic Myeloid Progenitor Cell Product Protects Neutropenic Mice From a Lethal Fungal Infection.

    PubMed

    Domen, Jos; Christensen, Julie L; Gille, Daphne; Smith-Berdan, Stephanie; Fong, Timothy; Brown, Janice M Y; Sedello, Anna K

    2016-01-01

    Severe neutropenia induced by chemotherapy or conditioning for hematopoietic cell transplantation often results in morbidity and mortality due to infection by opportunistic pathogens. A system has been developed to generate ex vivo-expanded mouse myeloid progenitor cells (mMPCs) that produce functional neutrophils in vivo upon transplantation in a pathogen challenge model. It has previously been demonstrated that transplantation of large numbers of freshly isolated myeloid progenitors from a single donor provides survival benefit in radiation-induced neutropenic mice. In the present work, an ex vivo-expanded and cryopreserved mMPC product generated from an allogeneic donor pool retains protective activity in vivo in a lethal fungal infection model. Infusion of the allogeneic pooled mMPC product is effective in preventing death from invasive Aspergillus fumigatus in neutropenic animals, and protection is dose dependent. Cell progeny from the mMPC product is detected in the bone marrow, spleen, blood, and liver by flow cytometry 1 week postinfusion but is no longer evident in most animals 4 weeks posttransplant. In this model, the ex vivo-generated pooled allogeneic mMPC product (i) expands and differentiates in vivo; (ii) is functional and prevents death from invasive fungal infection; and (iii) does not permanently engraft or cause allosensitization. These data suggest that an analogous ex vivo-expanded human myeloid progenitor cell product may be an effective off-the-shelf bridging therapy for the infectious complications that develop during hematopoietic recovery following hematopoietic cell transplantation or intensive chemotherapy. PMID:25812169

  10. Microspectroscopic Evidence of Cretaceous Bone Proteins

    PubMed Central

    Lindgren, Johan; Uvdal, Per; Engdahl, Anders; Lee, Andrew H.; Alwmark, Carl; Bergquist, Karl-Erik; Nilsson, Einar; Ekström, Peter; Rasmussen, Magnus; Douglas, Desirée A.; Polcyn, Michael J.; Jacobs, Louis L.

    2011-01-01

    Low concentrations of the structural protein collagen have recently been reported in dinosaur fossils based primarily on mass spectrometric analyses of whole bone extracts. However, direct spectroscopic characterization of isolated fibrous bone tissues, a crucial test of hypotheses of biomolecular preservation over deep time, has not been performed. Here, we demonstrate that endogenous proteinaceous molecules are retained in a humerus from a Late Cretaceous mosasaur (an extinct giant marine lizard). In situ immunofluorescence of demineralized bone extracts shows reactivity to antibodies raised against type I collagen, and amino acid analyses of soluble proteins extracted from the bone exhibit a composition indicative of structural proteins or their breakdown products. These data are corroborated by synchrotron radiation-based infrared microspectroscopic studies demonstrating that amino acid containing matter is located in bone matrix fibrils that express imprints of the characteristic 67 nm D-periodicity typical of collagen. Moreover, the fibrils differ significantly in spectral signature from those of potential modern bacterial contaminants, such as biofilms and collagen-like proteins. Thus, the preservation of primary soft tissues and biomolecules is not limited to large-sized bones buried in fluvial sandstone environments, but also occurs in relatively small-sized skeletal elements deposited in marine sediments. PMID:21559386

  11. Autoserum: An Optimal Supplement for Bone Marrow Mesenchymal Stem Cells of Liver-Injured Rats.

    PubMed

    Zhang, Qinglin; Sun, Xun; Ding, Jianxun; He, Ping; Liu, Yujia; Cheng, Hongjing; Zhou, Changlin; Meng, Xiangwei

    2015-01-01

    Mesenchymal stem cells (MSCs) are an attractive source for the clinical cell therapy of liver injury. Although the use of adult serum, platelet lysate, or cord blood serum solves some of the problems caused by fetal bovine serum (FBS), the allogeneic immune response, contamination, and donor-to-donor and donor-to-receptor differences still obstruct the application of MSCs. In this study, the influences of autoserum from liver-injured rats (LIRs) and allogeneic serum from healthy rats on the isolation and culture of bone marrow MSCs (BMSCs) were examined and compared to FBS. The results showed that BMSCs cultured with autoserum or allogeneic serum exhibited better MSC-specific morphology, lower rate of cell senescent, and higher proliferation kinetics than those with FBS. In addition, autoserum promoted the osteogenic differentiation potential of BMSCs as allogeneic serum did. Although there were no significant differences in proliferation activity, immunophenotypic characterization, and differentiation potential between BMSCs cultured with autoserum and those with allogeneic serum, the potential adverse immunological reactions in patients with allogeneic material transplantation must be considered. We therefore believe that the autoserum from liver-injured patients may be a better choice for MSC expansion to meet the needs of liver injury therapy. PMID:26089916

  12. [Bordetella bronchiseptica recurrent bacteraemia in a patient with bone marrow transplantation].

    PubMed

    Echeverri-Toro, Lina; Arango, Andrés; Ospina, Sigifredo; Agudelo, Carlos

    2015-01-01

    We report a case of recurrent bacteraemia caused by Bordetella bronchiseptica in an immunocompromised patient with a history of allogenic bone marrow transplantation for myelodysplastic syndrome, who was admitted to hospital with febrile syndrome. Bordetella bronchiseptica is an uncommon human pathogen which mainly affects immunocompromised patients, being a rare cause of bacteraemia. PMID:26849691

  13. [Bordetella bronchiseptica recurrent bacteraemia in a patient with bone marrow transplantation].

    PubMed

    Echeverri-Toro, Lina; Arango, Andrés; Ospina, Sigifredo; Agudelo, Carlos

    2015-01-01

    We report a case of recurrent bacteraemia caused by Bordetella bronchiseptica in an immunocompromised patient with a history of allogenic bone marrow transplantation for myelodysplastic syndrome, who was admitted to hospital with febrile syndrome. Bordetella bronchiseptica is an uncommon human pathogen which mainly affects immunocompromised patients, being a rare cause of bacteraemia.

  14. Role of fluoridated carbamide peroxide whitening gel in the remineralization of demineralized enamel: An in vitro study

    PubMed Central

    Bollineni, Swetha; Janga, Ravi Kumar; Venugopal, L.; Reddy, Indukuri Ravikishore; Babu, P. Ravisekhar; Kumar, Sunil S.

    2014-01-01

    Introduction: The use of self-administered carbamide peroxide bleaching gels has become increasingly popular for whitening of discolored vital teeth. Studies have reported that its use may induce increased levels of sensitivity and surface roughness of the tooth due to demineralization. This study evaluates the effect of fluoride addition to the bleaching agent – its remineralizing capacity and alterations in the whitening properties. Materials and Methods: Twenty-four extracted lower third molar teeth, with the pretreatment shade determined, were taken up in the study. Each tooth was sectioned into four and labeled as groups A, B, C, and D. The tooth quadrants in group A-C were demineralized; groups A and B were treated with 10% carbamide peroxide gel (group-A without fluoride and group-B with 0.463% fluoride addition) (no further treatment was carried out for group c) group-D remained as the control. The post-treatment shade was determined. The tooth samples were sectioned (approximately 200 μm) for evaluation under a light microscope. The depth of demineralization was analyzed at five different equidistant points. Statistical analysis was carried out with t-tests, accepting ≤0.05 as significant. Results and Conclusion: Addition of fluoride caused remineralization of demineralized enamel. The tooth whitening system showed that the remineralization properties did not affect the whitening properties. PMID:25254197

  15. A&M. Demineralization plant (TAN649). Steel door. Ralph M. Parsons 1480L/ANP/GA3649MS1. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    A&M. Demineralization plant (TAN-649). Steel door. Ralph M. Parsons 1480-L/ANP/GA-3-649-MS-1. Date: October 1958. Approved by INEEL Classification Office for public release. INEEL index code no. 034-0649-40-693-107443 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

  16. Selective removal of demineralized enamel using a CO2 laser coupled with near-IR reflectance imaging

    NASA Astrophysics Data System (ADS)

    Tom, Henry; Chan, Kenneth H.; Saltiel, Daniel; Fried, Daniel

    2015-02-01

    Detection and diagnosis of early dental caries lesions can be difficult due to variable tooth coloration, staining of the teeth and poor contrast between sound and demineralized enamel. These problems can be overcome by using near-infrared (NIR) imaging. Previous studies have demonstrated that lasers can be integrated with NIR imaging devices, allowing image-guided ablation. The aim of this study was to demonstrate that NIR light at 1500 - 1700 nm can be used to guide a 9.3-μm CO2 laser for the selective ablation of early demineralization on tooth occlusal surfaces. The occlusal surfaces of ten sound human molars were used in this in-vitro study. Shallow simulated caries lesions of varying depth and position were produced on tooth occlusal surfaces using a demineralization solution. Sequential NIR reflectance images at 1500 - 1700 nm were used to guide the laser for selective ablation of the lesion areas. Digital microscopy and polarization sensitive optical coherence tomography (PS-OCT) were used to assess the selectivity of removal. This study demonstrates that high contrast NIR reflectance images can be used for the image-guided laser ablation of early demineralization from tooth occlusal surfaces.

  17. In vitro assessment of a calcium-fluoroaluminosilicate glass-based desensitizer for the prevention of root surface demineralization.

    PubMed

    Miyajima, Hiroyuki; Ishimoto, Takuya; Ma, Sai; Chen, Jihua; Nakano, Takayoshi; Imazato, Satoshi

    2016-01-01

    The purpose of this study was to evaluate the ability of a calcium-fluoroaluminosilicate glass-based desensitizer (Nanoseal) to protect against root demineralization in vitro. Nanoseal was applied to human root dentin, which was immersed in acidic buffer for 72 h, or exposed to pH cycling by immersing in distilled water or mineralizing solution for 24 h intermediately during 48 h-acid attack. Demineralization was evaluated by μ-CT, and mineral loss (ML) and lesion depth (LD) were determined from mineral density profiles. ML and LD in all treatment groups were significantly smaller compared with control. The Nanoseal-treated group with pH cycling using mineralizing solution had the lowest ML and LD. Analysis using an EPMA demonstrated calcium and phosphorous were incorporated into the superficial layer of specimens in the Nanoseal-treated groups, suggesting Nanoseal modified the dentin surface, making it resistant to demineralization. Application of Nanoseal is an effective method for protecting root from demineralization. PMID:27251995

  18. Bone scanning in assessing viability of vascularized skeletal tissue transplants. [Rats

    SciTech Connect

    Lipson, R.A.; Dief, H.; Greyson, N.D.; Kawano, H.; Gross, A.E.; Langer, F.; Halloran, P.F.

    1981-01-01

    One hundred and eight bone scans using /sup 99m/Technetium methylene diphosphonate (MDP) were performed in rats undergoing vascularized and nonvascularized syngeneic and allogeneic transplants of the hind limb, and in control animals. A six-level system of grading the radionuclide uptake in the graft was used to evaluate healing or complications of the transplantation. Bone scanning was superior to other modalities in assessing viability of the graft. Bone scans were able to: (1) immediately confirm vascular patency, thus obviating angiography; (2) demonstrate differences in the rate of repair in syngeneic and allogeneic nonvascularized grafts; (3) sequentially assess vascularized allograft rejection; and (4) document long-term effects, such as bone atrophy due to disuse and early epiphyseal maturity.

  19. High-throughput allogeneic antibody detection using protein microarrays.

    PubMed

    Paul, Jed; Sahaf, Bita; Perloff, Spenser; Schoenrock, Kelsi; Wu, Fang; Nakasone, Hideki; Coller, John; Miklos, David

    2016-05-01

    Enzyme-linked immunosorbent assays (ELISAs) have traditionally been used to detect alloantibodies in patient plasma samples post hematopoietic cell transplantation (HCT); however, protein microarrays have the potential to be multiplexed, more sensitive, and higher throughput than ELISAs. Here, we describe the development of a novel and sensitive microarray method for detection of allogeneic antibodies against minor histocompatibility antigens encoded on the Y chromosome, called HY antigens. Six microarray surfaces were tested for their ability to bind recombinant protein and peptide HY antigens. Significant allogeneic immune responses were determined in male patients with female donors by considering normal male donor responses as baseline. HY microarray results were also compared with our previous ELISA results. Our overall goal was to maximize antibody detection for both recombinant protein and peptide epitopes. For detection of HY antigens, the Epoxy (Schott) protein microarray surface was both most sensitive and reliable and has become the standard surface in our microarray platform. PMID:26902899

  20. Allogeneic clonal mesenchymal stem cell therapy for refractory graft-versus-host disease to standard treatment: a phase I study.

    PubMed

    Yi, Hyeon Gyu; Yahng, Seung-Ah; Kim, Inho; Lee, Je-Hwan; Min, Chang-Ki; Kim, Jun Hyung; Kim, Chul Soo; Song, Sun U

    2016-01-01

    Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose (1×10(6) cells/kg), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial. PMID:26807024

  1. DNA profiling in peripheral blood, buccal swabs, hair follicles and semen from a patient following allogeneic hematopoietic stem cells transplantation

    PubMed Central

    LI, YA-TING; XIE, MING-KUN; WU, JIN

    2014-01-01

    Allogeneic peripheral blood stem cells transplantation (allo-PBSCT) or allogeneic bone marrow transplantation (allo-BMT) have been widely used to treat patients exhibiting certain severe illnesses. However, previous studies have shown that the biological materials of allo-PBSCT or allo-BMT recipients may not constitute credible materials for personal identification. In the present study, four types of commonly used samples were collected from a male individual following gender-matched allo-BMT. Autosomal short tandem repeat (STR) and Y-STR markers analysis, based on polymerase chain reaction, were used to evaluate the chimerism status. The results showed that the blood sample were all donor type, the buccal swab sample were mixed chimerism, and the sperm and hair follicle samples maintained a recipient origin of 100%. In conclusion, identical results were obtained by the two methods and it was confirmed that DNA extracted from hair follicles and sperm can be used as a reference for the pre-transplant genotype DNA profile of the recipient in the gender-match allo-BMT or -PBSCT. PMID:25279149

  2. Allogeneic hematopoietic SCT performed in non-HEPA filter rooms: initial experience from a single center in India.

    PubMed

    Kumar, R; Naithani, R; Mishra, P; Mahapatra, M; Seth, T; Dolai, T K; Bhargava, R; Saxena, R

    2009-01-01

    In developing countries, it is important to ascertain the safety of performing allogeneic hematopoietic SCT (HSCT) in single rooms without high-efficiency particulate air (HEPA) filters. We present our experience of performing 40 such transplants from July 2004 to November 2007. Source of stem cells was peripheral blood in 33, bone marrow in six and combined in one. G-CSF started from day +1. The indications were SAA-18, CML-7, AML-7, ALL-2, myelodysplastic syndrome-2 and thalassemia major-4. The median age was 19 years (range 2.2-46) with 29 male and 11 female participants. Antibacterial and antifungal prophylaxis was administered along with conditioning, and at the onset of fever, systemic antibiotics were started. Antifungal agents were added if fever persisted for 3 days. Median time for neutrophil engraftment was 10 days (range 8-17). Fever occurred in 38 (95%) for a median of 5 days (range 1-38), and blood cultures were positive in seven (17.5%). Systemic antibiotics were used in 95% and antifungals in 57.5% cases. The 30-day mortality was nil, and 100-day mortality was 1 (2.5%). After day 100, there were eight fatalities (20%) due to chronic GVHD-3, relapse-2, graft rejection-2, disseminated tuberculosis and aspergillosis-1. Our experience suggests that allogeneic HSCT can be safely performed in non-HEPA filter rooms in India. PMID:18794872

  3. Successful treatment of small cell variant anaplastic large cell lymphoma with allogeneic peripheral blood stem cell transplantation, and review of the literature.

    PubMed

    Imamura, Rie; Mouri, Fumihiko; Nomura, Kei; Nakamura, Takayuki; Oku, Eijiro; Morishige, Satoshi; Takata, Yuka; Seki, Ritsuko; Osaki, Koichi; Hashiguchi, Michitoshi; Yoshimoto, Koji; Ohshima, Koichi; Nagafuji, Koji; Okamura, Takashi

    2013-01-01

    The small cell variant of anaplastic large cell lymphoma (ALCL) presents in a nearly identical manner to the more common ALK(+) primary ALCL, with the exception that it is more frequently associated with leukemic involvement, and the prognosis has been reported to be poor. We report a 40-year-old Japanese male who was diagnosed with small cell variant ALCL with peripheral blood involvement stage IVB, age-adjusted international prognostic index 3. Conventional cytogenetics of the bone marrow aspirate specimen showed abnormal metaphases with the following karyotype: 47, XY, +X, t(2;5)(p23;q35). The patient was treated with acute lymphoblastic leukemia-oriented intensive chemotherapy. He underwent allogeneic peripheral blood stem cell transplantation from his HLA-DR1 locus mismatch sister. Prior to transplant, the patient had residual lymphadenopathy considered to be in partial remission. As of August 2012, the patient has achieved 18 months of continuous complete remission (CCR), with a Karnofsky score of 100 %. We have identified a total of seven cases of small cell variant ALCL treated with allogeneic hematopoietic stem cell transplantation (HSCT) in the literature. Of these, no relapse was reported, and four patients were CCR more than 1 year. Allogeneic HSCT appears to represent a promising treatment option for small cell variant ALCL. PMID:23264126

  4. Financial burden in recipients of allogeneic hematopoietic cell transplantation.

    PubMed

    Khera, Nandita; Chang, Yu-hui; Hashmi, Shahrukh; Slack, James; Beebe, Timothy; Roy, Vivek; Noel, Pierre; Fauble, Veena; Sproat, Lisa; Tilburt, Jon; Leis, Jose F; Mikhael, Joseph

    2014-09-01

    Although allogeneic hematopoietic cell transplantation (HCT) is an expensive treatment for hematological disorders, little is known about the financial consequences for the patients who undergo this procedure. We analyzed factors associated with its financial burden and its impact on health behaviors of allogeneic HCT recipients. A questionnaire was retrospectively mailed to 482 patients who underwent allogeneic HCT from January 2006 to June 2012 at the Mayo Clinic, to collect information regarding current financial concerns, household income, employment, insurance, out-of-pocket expenses, and health and functional status. A multivariable logistic regression analysis identified factors associated with financial burden and treatment nonadherence. Of the 268 respondents (56% response rate), 73% reported that their sickness had hurt them financially. All patients for whom the insurance information was available (missing, n = 13) were insured. Forty-seven percent of respondents experienced financial burden, such as household income decreased by >50%, selling/mortgaging home, or withdrawing money from retirement accounts. Three percent declared bankruptcy. Younger age and poor current mental and physical functioning increased the likelihood of financial burden. Thirty-five percent of patients reported deleterious health behaviors because of financial constraints. These patients were likely to be younger, have lower education, and with a longer time since HCT. Being employed decreased the likelihood of experiencing financial burden and treatment nonadherence due to concern about costs. A significant proportion of allogeneic HCT survivors experience financial hardship despite insurance coverage. Future research should investigate potential interventions to help at-risk patients and prevent adverse financial outcomes after this life-saving procedure.

  5. Aspergillus Thyroiditis after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Ataca, Pinar; Atilla, Erden; Saracoglu, Pelin; Yilmaz, Gulden; Civriz Bozdag, Sinem; Toprak, Selami Kocak; Yuksel, Meltem Kurt; Ceyhan, Koray; Topcuoglu, Pervin

    2015-01-01

    Aspergillus thyroiditis is a rare disorder detected in immunocompromised patients during disseminated infections. Early management is essential to prevent high mortality. A 61-year-old allogeneic stem cell male recipient presented with painful thyroid nodular enlargement. He had low TSH and low free T4 levels. The thyroid ultrasound showed a hypoechoic nodule; biopsy indicated suppurative Aspergillus thyroiditis. He was successfully treated by amphotericin B. PMID:26640727

  6. The efficacy of laser-assisted in-office bleaching and home bleaching on sound and demineralized enamel

    PubMed Central

    Akbari, Majid; Mohammadpour, Sakineh

    2015-01-01

    Aims: This study investigated the effectiveness of laser-assisted in-office bleaching and home-bleaching in sound and demineralized enamel. Materials and Methods: The sample consisted of 120 freshly-extracted bovine incisors. Half of the specimens were stored in a demineralizing solution to induce white spot lesions. Following exposure to a tea solution for 7.5 days, the specimens were randomly assigned to 4 groups of 30 according to the type of enamel and the bleaching procedure employed. Groups 1 and 2 consisted of demineralized teeth subjected to in-office bleaching and home bleaching, whereas in groups 3 and 4, sound teeth were subjected to in-office and home bleaching, respectively. A diode laser (810 nm, 2 W, continuous wave, four times for 15 seconds each) was employed for assisting the in-office process. The color of the specimens was measured before (T1) and after (T2) staining and during (T3) and after (T4) the bleaching procedures using a spectrophotometer. The color change (ΔE) between different treatments stages was compared among the groups. Results: There were significant differences in the color change between T2 and T3 (ΔE T2–T3) and T2 and T4 (ΔE T2–T4) stages among the study groups (p<0.05). Pairwise comparison by Duncan test revealed that both ΔET2–T3 and ΔET2–T4 were significantly greater in demineralized teeth submitted to laser-assisted in-office bleaching (group 1) as compared to the other groups (P< 0.05). Conclusion: Laser-assisted in-office bleaching could provide faster and greater whitening effect than home bleaching on stained demineralized enamel, but both procedures produced comparable results on sound teeth. PMID:26877590

  7. Bone disease in adult patients with β-thalassaemia major: a case-control study.

    PubMed

    Baldini, Marina; Forti, Stella; Orsatti, Alessandra; Ulivieri, Fabio Massimo; Airaghi, Lorena; Zanaboni, Laura; Cappellini, Maria Domenica

    2014-02-01

    Despite the extraordinary improvements carried out in diagnostic and therapeutic management of thalassaemia major over the past few decades, bone demineralization is still a common finding, even in optimally treated patients. The relationships between bone density and several clinical characteristics or hematological markers have been described, and many factors contributing to demineralization have been identified; among them endocrine complications seem to play an important role. Nevertheless, the complex etiological mechanisms of this heterogeneous osteopathy still remains incompletely clarified. While previous studies focused on the characteristics of thalassaemic patients affected from bone demineralization, we conducted a case-control study focused on thalassaemic patients free from bone disease, aimed to detect the distinctive characteristics and any possible protective feature. Among a large cohort of 150 adult patients with β-thalassaemia major, we enrolled 20 patients with normal bone mineralization and 20 patients with osteoporosis matched for gender, BMI, age at first transfusion, serum ferritin and pre-transfusional hemoglobin (Hb) levels. The differences in demographic, clinical and endocrinological profiles were investigated, correcting for physical and hematological features known as confounding variables. The comparison of the two groups for biochemical parameters and endocrine function showed a protective role of normal gonadic function and IGF-1 levels against osteoporosis, and a similar influence of hypoparathyroidism. Treatment-corrected hypothyroidism and diabetes seemed not to affect bone mineralization. In conclusion, from a different perspective our results corroborate the role of endocrinopathies in thalassaemic osteopathy, and once again underline the crucial importance of an early and multi-disciplinary intervention in preventing bone complications in thalassaemic patients. PMID:22179745

  8. New frontiers in pediatric allogeneic stem cell transplantation

    PubMed Central

    Talano, Julie-An M.; Pulsipher, Michael A.; Symons, Heather J.; Militano, Olga; Shereck, Evan B.; Giller, Roger H.; Hancock, Laura; Morris, Erin; Cairo, Mitchell S.

    2015-01-01

    The inaugural meeting of “New Frontiers in Pediatric Allogeneic Stem Cell Transplantation” organized by the Pediatric Blood and Transplant Consortium (PBMTC) was held at the American Society of Pediatric Hematology and Oncology Annual Meeting. This meeting provided an international platform for physicians and investigators active in the research and utilization of pediatric allogeneic stem cell transplantation (AlloSCT) in children and adolescents with malignant and non-malignant disease, to share information and develop future collaborative strategies. The primary objectives of the conference included: 1) to present advances in AlloSCT in pediatric ALL and novel pre- and post-immunotherapy; 2) to highlight new strategies in alternative allogeneic stem cell donor sources for children and adolescents with non-malignant hematological disorders; 3) to discuss timing of immune reconstitution after AlloSCT and methods of facilitating more rapid recovery of immunity; 4) to identify strategies of utilizing AlloSCT in pediatric myeloproliferative disorders (MPD); 5) to develop diagnostic and therapeutic approaches to hematological complications post pediatric AlloSCT; 6) to enhance the understanding of new novel cellular therapeutic approaches to pediatric malignant and non-malignant hematological disorders; and 7) to discuss optimizing drug therapy in pediatric recipients of AlloSCT. This paper will provide a brief overview of the conference. PMID:24820213

  9. Allogeneic Antigen Composition for Preparing Universal Cancer Vaccines

    PubMed Central

    Balashova, Elena E.

    2016-01-01

    Recently it was demonstrated that tumors induce specific changes to the surface of human endothelial cells thereby providing the basis for designing endothelial cell-based vaccines that directly target antigens expressed by the tumor endothelium. The present report extends these studies in vitro by investigating the efficacy of allogeneic antigens with regard to their ability to target immune responses against the tumor vasculature since alloantigens simplify vaccine development and implementation in clinical practice. We demonstrated that allogeneic SANTAVAC (Set of All Natural Target Antigens for Vaccination Against Cancer), which presents a specifically prepared composition of cell surface antigens from tumor-stimulated endothelial cells, allows targeting of the tumor vasculature with efficacy of 17, where efficacy represents the killing rate of target cells before normal cells are adversely affected, and efficacy of 60, where efficacy represents the fold decrease in the number of target cells and directly relates to tumor growth arrest. These data suggest that allogeneic SANTAVAC may be considered an antigenic composition that following administration in the presence of respective adjuvants may be clinically tested as a therapeutic or prophylactic universal cancer vaccine without adverse side effects to the normal vasculature. PMID:27781211

  10. Surgical technique for allogeneic uterus transplantation in macaques

    PubMed Central

    Obara, Hideaki; Kisu, Iori; Kato, Yojiro; Yamada, Yohei; Matsubara, Kentaro; Emoto, Katsura; Adachi, Masataka; Matoba, Yusuke; Umene, Kiyoko; Nogami, Yuya; Banno, Kouji; Tsuchiya, Hideaki; Itagaki, Iori; Kawamoto, Ikuo; Nakagawa, Takahiro; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Saiki, Yoko; Sato, Shin-ichi; Nakagawa, Kenshi; Shiina, Takashi; Aoki, Daisuke; Kitagawa, Yuko

    2016-01-01

    No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac artery. Before perfusion, 150 mL of whole blood was obtained from the donor for subsequent blood transfusion to the recipient. Four uterine grafts were orthotopically transplanted to recipients. End-to-side anastomosis was performed to the iliac vessels on one side in case 1 and iliac vessels on both sides in case 2; aorto-aorto/cavo-caval anastomosis was performed in cases 3 and 4. Arterial blood flow of the uterine grafts was determined by intraoperative indocyanine green (ICG) angiography. ICG angiography results showed sufficient blood flow to all uterine grafts, and anaemia did not progress. Under appropriate immune suppression, all recipients survived for more than 90 days post-transplantation, without any surgical complications. We describe a surgical technique for allogeneic UTx in cynomolgus macaques. PMID:27786258

  11. Acute phase serum proteins in syngeneic and allogeneic mouse pregnancy.

    PubMed Central

    Waites, G T; Bell, A M; Bell, S C

    1983-01-01

    The levels of two murine acute phase proteins, serum amyloid P component (SAP) and haptoglobin, have been measured in the serum of C57BL/10 female mice during syngeneic and allogeneic pregnancy. Both syngeneic and allogeneic pregnancy resulted in alterations in the levels of these proteins as compared to those observed in virgin females. Syngeneic mating resulted in an increase in concentration of both proteins during the final 3 days of pregnancy. During allogeneic pregnancy, SAP levels, after a transient increase on day 4, rose from days 6-8 and, after remaining relatively stable, increased from day 12 to reach maximum levels on day 18 of pregnancy. Levels fell dramatically during the immediate post-partum period. In contrast, although levels of haptoglobin also increased from days 6-8, for the remainder of pregnancy these increased levels remained stable. The implications of these findings are discussed in relation to the mechanisms of regulation of acute phase reactants and the immunological relationship between the mother and fetus. PMID:6409477

  12. SHIPi Enhances Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Fernandes, Sandra; Brooks, Robert; Gumbleton, Matthew; Park, Mi-Young; Russo, Christopher M.; Howard, Kyle T.; Chisholm, John D.; Kerr, William G.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) is a highly effective procedure enabling long-term survival for patients with hematologic malignancy or heritable defects. Although there has been a dramatic increase in the success rate of HSCT over the last two decades, HSCT can result in serious, sometimes untreatable disease due to toxic conditioning regimens and Graft-versus-Host-Disease. Studies utilizing germline knockout mice have discovered several candidate genes that could be targeted pharmacologically to create a more favorable environment for transplant success. SHIP1 deficiency permits improved engraftment of hematopoietic stem-progenitor cells (HS-PCs) and produces an immunosuppressive microenvironment ideal for incoming allogeneic grafts. The recent development of small molecule SHIP1 inhibitors has opened a different therapeutic approach by creating transient SHIP1-deficiency. Here we show that SHIP1 inhibition (SHIPi) mobilizes functional HS-PC, accelerates hematologic recovery, and enhances donor HS-PC engraftment in both allogeneic and autologous transplant settings. We also observed the expansion of key cell populations known to suppress host-reactive cells formed during engraftment. Therefore, SHIPi represents a non-toxic, new therapeutic that has significant potential to improve the success and safety of therapies that utilize autologous and allogeneic HSCT. PMID:26052545

  13. Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering.

    PubMed

    Montjovent, Marc-Olivier; Mark, Silke; Mathieu, Laurence; Scaletta, Corinne; Scherberich, Arnaud; Delabarde, Claire; Zambelli, Pierre-Yves; Bourban, Pierre-Etienne; Applegate, Lee Ann; Pioletti, Dominique P

    2008-03-01

    Fetal bone cells were shown to have an interesting potential for therapeutic use in bone tissue engineering due to their rapid growth rate and their ability to differentiate into mature osteoblasts in vitro. We describe hereafter their capability to promote bone repair in vivo when combined with porous scaffolds based on poly(l-lactic acid) (PLA) obtained by supercritical gas foaming and reinforced with 5 wt.% beta-tricalcium phosphate (TCP). Bone regeneration was assessed by radiography and histology after implantation of PLA/TCP scaffolds alone, seeded with primary fetal bone cells, or coated with demineralized bone matrix. Craniotomy critical size defects and drill defects in the femoral condyle in rats were employed. In the cranial defects, polymer degradation and cortical bone regeneration were studied up to 12 months postoperatively. Complete bone ingrowth was observed after implantation of PLA/TCP constructs seeded with human fetal bone cells. Further tests were conducted in the trabecular neighborhood of femoral condyles, where scaffolds seeded with fetal bone cells also promoted bone repair. We present here a promising approach for bone tissue engineering using human primary fetal bone cells in combination with porous PLA/TCP structures. Fetal bone cells could be selected regarding osteogenic and immune-related properties, along with their rapid growth, ease of cell banking and associated safety. PMID:18178142

  14. Living Bones, Strong Bones

    NASA Video Gallery

    In this classroom activity, engineering, nutrition, and physical activity collide when students design and build a healthy bone model of a space explorer which is strong enough to withstand increas...

  15. Evaluation of increased cesium loading on submerged demineralizer system (SDS) zeolite beds

    SciTech Connect

    Not Available

    1981-05-01

    A Submerged Demineralizer System (SDS) is being installed at the Three Mile Island Unit (TMI-2) Nuclear Power Station for decontamination of the Containment Building (CB) sump water and Reactor Coolant System (RCS) water. A Department of Energy (DOE) Task Force was assembled to evaluate the relative technical and financial benefits in storing, shipping, treating, and disposing of SDS zeolite liners, assuming that the liners will be loaded to a level higher than that (10,000 Ci/liner) originally planned by General Public Utilities (GPU). The DOE-SDS Task Force concludes that it is technically feasible to load the zeolite liners used in the SDS to levels up to 60,000 Ci of cesium per liner without additional preoperational testing. This would result in approximately ten such liners. The Task Force further concludes that these liners can be safely handled, stored, transported, and vitrified.

  16. Influence of different demineralization treatments on physicochemical structure and thermal degradation of biomass.

    PubMed

    Jiang, Long; Hu, Song; Sun, Lun-shi; Su, Sheng; Xu, Kai; He, Li-mo; Xiang, Jun

    2013-10-01

    To study the catalytic role of alkali and alkaline earth metallic species and eliminate their negative impact during biomass thermal utilization, different leaching methods have been applied in numerous experiments. Thus it is necessary to investigate the potential influence on biomass physicochemical structure using different agents. Rice straw was selected to study the demineralization impact on physicochemical structure and pyrolysis characteristics. It is shown that strong acid leaching exhibited higher removal efficiency of minerals, but it introduced more notable impact on physicochemical structure of biomass comparing to water and weak acid leaching. Different leaching methods give chance to study catalysis characteristics of intrinsic metals on biomass thermal reaction. Contrast to alkaline earth metals especially Ca hindering thermal decomposition, alkali metals promoted this reaction obviously. In addition, comparing to physicochemical structure changes created by leaching process, the influence of removal of minerals played the dominant role in biomass thermal behavior. PMID:23941708

  17. Effect of a lactose-containing sweetener on root dentine demineralization in situ.

    PubMed

    Aires, C P; Tabchoury, C P M; Del Bel Cury, A A; Cury, J A

    2002-01-01

    Since lactose has been used as an excipient in powdered sweeteners, we evaluated its effect on dentine demineralization, in an in situ crossover study. Twelve adult volunteers wore palatal appliances containing 4 blocks of bovine root dentine, which were submitted 4 times a day to: distilled water (negative control), aqueous solution of powdered sweetener (Zero Cal); experimental group), 1.5% lactose solution (active group), 1.5% sucrose solution (positive control). After 15 days, microhardness was determined on dentine surface (SMH) and on the sectioned blocks (CSMH). All groups presented statistical differences in SMH before and after the treatments; water increased, while sweetener, lactose and sucrose decreased SMH. By CSMH, the only significant difference was observed after sucrose treatment. The data suggest that sweeteners containing lactose as a bulking agent may be cariogenic for root dentine.

  18. The requirement of zinc and calcium ions for functional MMP activity in demineralized dentin matrices

    PubMed Central

    Tezvergil-Mutluay, Arzu; Agee, Kelli A.; Hoshika, Tomohiro; Carrilho, Marcela; Breschi, Lorenzo; Tjäderhane, Leo; Nishitani, Yoshihiro; Carvalho, Ricardo M.; Looney, Stephen; Tay, Franklin R.; Pashley, David H.

    2010-01-01

    The progressive degradation of resin-dentin bonds is due, in part, to the slow degradation of collagen fibrils in the hybrid layer by endogenous matrix metalloproteinases (MMPs) of the dentin matrix. In in vitro durability studies, the storage medium composition might be important because the optimum activity of MMPs requires both zinc and calcium. Objective This study evaluated the effect of different storage media on changes in matrix stiffness, loss of dry weight or solubilization of collagen from demineralized dentin beams incubated in vitro for up to 60 days. Methods Dentin beams (1×2×6mm) were completely demineralized in 10% phosphoric acid. After baseline measurements of dry mass and elastic modulus (E) (3-point bending, 15% strain) the beams were divided into 5 groups (n=11/group) and incubated at 37°C in either media containing both zinc and calcium designated as complete medium(CM), calcium-free medium, zinc-free medium, a doubled-zinc medium or water. Beams were retested at 3, 7, 14, 30, and 60 days of incubation. The incubation media was hydrolyzed with HCl for the quantitation of hydroxyproline (HOP) as an index of solubilization of collagen by MMPs. Data were analyzed using repeated measures of ANOVA. Results Both the storage medium and storage time showed significant effects on E, mass loss and HOP release (p<0.05). The incubation in CM resulted in relatively rapid and significant (p<0.05) decreases in stiffness, and increasing amounts of mass loss. The HOP content of the experimental media also increased with incubation time but was significantly lower (p<0.05) than in the control CM medium, the recommended storage medium. Conclusions The storage solutions used to age resin-dentin bonds should be buffered solutions that contain both calcium and zinc. The common use of water as an aging medium may underestimate the hydrolytic activity of endogenous dentin MMPs. PMID:20688380

  19. Effect of Fluoride Concentration on Reduction of Enamel Demineralization According to the Cariogenic Challenge.

    PubMed

    Noronha, Mayara Dos Santos; Romão, Dayse Andrade; Cury, Jaime Aparecido; Tabchoury, Cínthia Pereira Machado

    2016-01-01

    Fluoride present in toothpaste at 1,100 µg/g is considered effective on caries control. However, under high cariogenic challenge due to increasing sugar exposure, higher fluoride concentration (5,000 µg/g) could be necessary to compensate the unbalance on caries process. This was tested in a pH-cycling regimen, which evaluated the effect of fluoride concentration relative to toothpaste on reduction of enamel demineralization under conditions of two levels of cariogenic challenge. Enamel slabs (n=20) were subjected to two pH-cycling regimens, simulating 8x and 16x/day sugar exposure and were treated with solutions containing: 0 (no fluoride), 275 or 1,250 µg F/mL, resulting in 6 treatment groups: 4-h/0-F; 8-h/0-F; 4-h/275-F; 8-h/275-F; 4-h/1,250-F and 8-h/1,250-F. The 275 and 1,250 µg F/mL concentrations simulate mouth salivary dilution when 1,100 and 5,000 µg/g toothpastes are used. Enamel demineralization was assessed by surface (%SHL) and cross-sectional hardness. Fluoride taken up by enamel was also evaluated. Data were analyzed by ANOVA one-way and Tukey's test. The treatment with 1,250 µg F/mL significantly reduced %SHL compared with 275 µg F/mL (p<0.05), irrespective the level of cariogenic challenge (4-h/1,250-F vs. 4-h/275-F and 8-h/1,250-F vs 8-h/275-F comparisons, respectively). These data were supported by fluoride concentration found in enamel. These findings suggest that higher fluoride concentrations could partly compensate the greater caries risk under higher cariogenic challenge due to increasing sugar exposure. PMID:27652699

  20. Evaluation of some properties of fermented milk beverages that affect the demineralization of dental enamel.

    PubMed

    Lodi, Carolina Simonetti; Sassaki, Kikue Takebayashi; Fraiz, Fabian Calixto; Delbem, Alberto Carlos Botazzo; Martinhon, Cleide Cristina Rodrigues

    2010-01-01

    The aim of this in vitro study was to evaluate the erosive capacity of fermented milk beverages, as well as some of their properties that affect the demineralization of dental enamel (pH, buffering capacity, fluoride, calcium and phosphorus contents). Three different batches of 6 commercial brands of fermented milk beverages were analyzed. pH evaluation was accomplished using a potentiometer. The buffering capacity was measured by adding 1 mol L-1 NaOH. Fluoride concentration was assessed by an ion specific electrode after hexamethyldisiloxane-facilitated diffusion, and calcium and phosphorus concentrations were assessed by a colorimetric test using a spectrophotometer. Sixty specimens of bovine enamel were randomly assigned to 6 groups (n = 10). They were exposed to 4 cycles of demineralization in the fermented milk and remineralization in artificial saliva. Enamel mineral loss was determined by surface microhardness (%SMHC) and profilometric tests. The samples' pH ranged from 3.51 to 3.87; the buffering capacity ranged from 470.8 to 804.2 microl of 1 mol L(-1) NaOH; the fluoride concentration ranged from 0.027 to 0.958 microgF/g; the calcium concentration ranged from 0.4788 to 0.8175 mgCa/g; and the phosphorus concentration ranged from 0.2662 to 0.5043 mgP/g. The %SMHC ranged from -41.0 to -29.4. The enamel wear ranged from 0.15 microm to 0.18 microm. In this in vitro study, the fermented milk beverages did not promote erosion of the dental enamel, but rather only a superficial mineral loss.

  1. Bone Tumor

    MedlinePlus

    ... most common types of primary bone cancer are: • Multiple myeloma. Multiple myeloma is the most common primary bone cancer. It ... Any bone can be affected by this cancer. Multiple myeloma affects approximately six people per 100,000 each ...

  2. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  3. The mechanically stable steam sterilization of bone grafts.

    PubMed

    Draenert, G F; Delius, M

    2007-03-01

    Bone allografts are the standard material used in augmentative bone surgery. However, steam-sterilized bone has a low mechanical stability and limited ossification based on low strain-adapted bone remodelling. Here we describe a new technique which allows the bone to be autoclaved without losing its mechanical stability and osteoconductivity. The compression strength of the new material was compared with steam-sterilized and fresh bone based on mechanical testing using bone cylinders (n=30/group). Allogeneic new material and fresh bone were press-fit implanted into rabbit patellar grooves and examined under fluorescent light and conventional microscopy. Initial healing was assessed after 30 d (n=5/group). Osseous integration and remodelling was studied after 100 d (n=12/group). Steam-sterilized bone showed no mechanical stability, whereas the new material was stiff and had compression curves similar to fresh bone; both groups showed equal degrees of direct ossification after 30 d, advanced bony ingrowth and remodelling after 100 d, and similar ingrowth depths on histomorphometric analysis. The new method preserved the stiffness and osteoconductivity of bone after steam sterilization, and microstructure, mineralization, and composition were conserved. This technique could be useful for bone banking in Third World countries.

  4. Preventive azithromycin treatment reduces noninfectious lung injury and acute graft-versus-host disease in a murine model of allogeneic hematopoietic cell transplantation.

    PubMed

    Radhakrishnan, Sabarinath Venniyil; Palaniyandi, Senthilnathan; Mueller, Gunnar; Miklos, Sandra; Hager, Max; Spacenko, Elena; Karlsson, Fridrik J; Huber, Elisabeth; Kittan, Nicolai A; Hildebrandt, Gerhard C

    2015-01-01

    Noninfectious lung injury and acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) are associated with significant morbidity and mortality. Azithromycin is widely used in allogeneic HCT recipients for pulmonary chronic GVHD, although current data appear controversial. We induced GVHD and noninfectious lung injury in lethally irradiated B6D2F1 mice by transplanting bone marrow and splenic T cells from allogeneic C57BL/6 mice. Experimental groups were treated with oral azithromycin starting on day 14 until the end of week 6 or week 14 after transplantation. Azithromycin treatment resulted in improved survival and decreased lung injury; the latter characterized by improved pulmonary function, reduced peribronchial and perivascular inflammatory cell infiltrates along with diminished collagen deposition, and a decrease in lung cytokine and chemokine expression. Azithromycin also improved intestinal GVHD but did not affect liver GVHD at week 6 early after transplantation. At week 14, azithromycin decreased liver GVHD but had no effect on intestinal GVHD. In vitro, allogeneic antigen-presenting cell (APC)- dependent T cell proliferation and cytokine production were suppressed by azithromycin and inversely correlated with relative regulatory T cell (Treg) expansion, whereas no effect was seen when T cell proliferation occurred APC independently through CD3/CD28-stimulation. Further, azithromycin reduced alloreactive T cell expansion but increased Treg expansion in vivo with corresponding downregulation of MHC II on CD11c(+) dendritic cells. These results demonstrate that preventive administration of azithromycin can reduce the severity of acute GVHD and noninfectious lung injury after allo-HCT, supporting further investigation in clinical trials.

  5. Gravity, Calcium, and Bone: Update, 1989

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Morey-Holton, Emily

    1991-01-01

    Some of the results of recent short-term flights and ground-based experiments that have contributed new insights into skeletal adaptation, calcium metabolism, and growth processes in 0 g, are highlighted. After 6 months in space, bone demineralization, invariably involving the os calcis, was found not to extend to the lumbar spine in 4 exercising cosmonauts. A flight experiment in the Space Shuttle crew has documented the early events in the calcium endocrine system during spaceflight. On the ground, brief and long-term bed rest studies of healthy volunteers in the head-down tile (HDT) model of weightlessness were completed. The skeleton of the adult male responds more rapidly to unloading than previously recognized. Regional changes in bone density can be quantified in only 30 days, are highly individual, and follow the direction of gravitational forces in the HDT model during inactivity. Bone biopsy results in healthy volunteers after bed rest differ from results in paraplegics from the same sampling site. Flight experiments in growing rats reveal changes in the composition of bone mineral and matrix in the femur postflight that were found to be highly regional and suggestive of an effect of gravity on mineral distribution. These observations may be relevant to the results from an earlier Cosmos flight where artificial gravity in space was found to maintain bone strength, but not to correct the radial growth deficit.

  6. Orthotopic bone transplantation in mice. III. Methods of reducing the immune response and their effect on healing

    SciTech Connect

    Kliman, M.; Halloran, P.F.; Lee, E.; Esses, S.; Fortner, P.; Langer, F.

    1981-01-01

    Various methods of reducing the immune response to allogeneic bone grafts, either by pretreating the graft or by immunosuppressing the recipient, were compared. Tibial grafts from B10.D2 mice, either untreated or pretreated in various ways, were transplanted into B10 recipients. The antibody response was followed and the extent of bone healing at 4 months was assessed. Pretreatment of the graft by X-irradiation, freezing, or by incubation in alloantisera (either anti-H-2 or anti-Ia) reduced or abolished the immunogenicity of the graft. Immunosuppression of the recipient with methotrexate or antilymphocyte serum (ALS) also greatly depressed the antibody response. But when healing was assessed, none of these treatments except ALS improved the delayed healing of the bone allografts. The reason for this failure was probably that X-irradiation, freezing, alloantiserum pretreatment, and methotrexate all interfered with bone healing directly, whereas ALS did not. We conclude that many methods will reduce the immune response to allogeneic bone, but that only ALS will improve the healing of the allogeneic bone. Furthermore, as a corollary to the observation that pretreatment with anti-Ia serum markedly reduced the immunogenicity of bone allografts, we conclude that much of the immunogenicity of bone allografts is attributable to a population of Ia-positive cells.

  7. 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.

  8. An alternative model of vascularized bone marrow transplant: partial femur transplantation.

    PubMed

    Chen, Jian-Wu; Chen, Chen; Su, Ying-Jun; Yan, Lun; Wang, Shi-Ping; Guo, Shu-Zhong

    2014-12-01

    The vascularized whole femur transplantation model is one of the commonly used vascularized bone marrow transplant models. It involves technical complexity and morbidities. To optimize this model, we took 2/3 femur as the carrier of bone marrow cells, and developed a vascularized partial femur model. Four experimental groups were carried out, namely, the syngeneic partial femur transplantation, allogeneic partial femur transplantation with or without cyclosporine A, and allogeneic whole femur transplantation with cyclosporine A. The results showed that the partial femur model was technically simpler and shortened the operative and ischemia time compared to the whole femur model. Gross and histologic appearance confirmed the viability of femur, and its bone marrow inside the bone could also maintain normal morphologically at 60-day posttransplant. Besides, donor multilineage chimerism could be continuously detected in immunosuppressed allogeneic partial femur recipients at 1-, 2-, 3-, 4-, and 8-week posttransplant, and it showed no significant differences when compared with whole femur transplantation. Meanwhile, long-term engraftment of donor-origin cells was also confirmed in recipients' bone marrow, lymph nodes, and spleen, but not in thymus. Therefore, the vascularized partial femur can serve as a continuous resource of bone morrow cells and may provide a useful tool for the study of immune tolerance in vascularized composite allotransplantation.

  9. Psychosocial aspects of haematopoietic stem cell donation for allogeneic transplantation: how family donors cope with this experience.

    PubMed

    Munzenberger, N; Fortanier, C; Macquart-Moulin, G; Faucher, C; Novakovitch, G; Maraninchi, D; Moatti, J P; Blaise, D

    1999-01-01

    Peripheral blood stem cell (PBSC) allogeneic transplantation is an innovative medical procedure which has many advantages in comparison with bone marrow (BM) transplantation, but it involves administering haematopoietic growth factors (HGFs) to donors, the long-term physiological effects of which have not yet been established. The main aim of the present study was to analyse how family PBSC donors cope when confronted with this particular risk context. In addition to data collected on the personal and social aspects of the donors' experience, questionnaires were used to measure their quality of life (pain and anxiety) before, during and after donation, and they were subsequently interviewed in depth by a psychologist. Twenty-two donors participated in this study. They did not all react to the experience of blood cell donation in the same way, in terms of their own personal feelings, attitudes towards the donation, their relationships with the other members of the family, and their awareness of the risk involved. PMID:10202783

  10. Ocular complications of bone marrow transplantation.

    PubMed

    Livesey, S J; Holmes, J A; Whittaker, J A

    1989-01-01

    Thirty-four patients who had undergone bone marrow transplantation (BMT) were examined; 83.3% of those who received single shot and none of those who received fractionated total body irradiation (TBI) developed cataracts. The use of steroids to treat chronic Graft Versus Host Disease (GVHD) produced more severe cataracts in those who had allogeneic transplants after single shot TBI, but follow-up has not been long enough to assess their effect following fractionated TBI. Keratoconjunctivitis sicca (KCS) was seen in 81.8% of patients with chronic GVHD and in 33.3% of patients after autologous BMT. PMID:2693135

  11. Bone and bone turnover.

    PubMed

    Crofton, Patricia M

    2009-01-01

    Children with cancer are exposed to multiple influences that may adversely affect bone health. Some treatments have direct deleterious effects on bone whilst others may have indirect effects mediated through various endocrine abnormalities. Most clinical outcome studies have concentrated on survivors of acute lymphoblastic leukaemia (ALL). There is now good evidence that earlier treatment protocols that included cranial irradiation with doses of 24 Gy or greater may result in growth hormone deficiency and low bone mineral density (BMD) in the lumbar spine and femoral neck. Under current protocols, BMD decreases during intensive chemotherapy and fracture risk increases. Although total body BMD may eventually return to normal after completion of chemotherapy, lumbar spine trabecular BMD may remain low for many years. The implications for long-term fracture risk are unknown. Risk factors for low BMD include high dose methotrexate, higher cumulative doses of glucocorticoids, male gender and low physical activity. BMD outcome in non-ALL childhood cancers has been less well studied but there is evidence that survivors of childhood brain or bone tumours, and survivors of bone marrow transplants for childhood malignancy, all have a high risk of long-term osteopenia. Long-term follow-up is required, with appropriate treatment of any endocrine abnormalities identified.

  12. Use of frozen cranial vault bone allografts in the repair of extensive cranial bone defects.

    PubMed

    Vanaclocha, V; Bazan, A; Saiz-Sapena, N; Paloma, V; Idoate, M

    1997-01-01

    In cranioplasty complexity is proportional to the size of the detect, particularly if greater than 50 cm2. If the patient's own bone flap is not available, allogenic frozen bone graft can be used instead. Between June 1990 and June 1995 twenty cranioplasties with allogenic frozen bone grafts were performed. Age of patients ranged between 23 and 63 years (average 38.4 years). Male/female ratio was 2:1.7. Size of craniectomy ranged between 65 and 150 cm2 (average 83.3 cm2). Follow-up ranged between 10 and 58 months (average 41 months). Donors were tested to rule out transmissible diseases, infections, sepsis and/or cancer. Bone grafts were removed under aseptic conditions, microbiological cultures were taken, wrapped in a gauze soaked with Gentamicin sulphate and Bacitracin, sealed in three sterilised vinyl plastic bags, and stored in a deep freezer for a minimum of 30 days (range 36-93 days, average 67 days), at a temperature of -80 degrees C. Grafts were placed in the defect after a step was carved on its borders to facilitate the contact between host and graft. Vancomycin 1 g. IV/12 hours and Ceftriaxone 1 g. IV/12 hours were administered for five days. Grafts were covered by means of scalp flaps. Only one required a musculocutaneous free flap. None was exposed, extruded or had to be removed. Plain skull X-ray studies showed progressive remodelling of the grafts. Partial resorption was observed in two (2/20, 10%) and loss of thickness in another 3/20 (15%), but with no changes in the contour. Biopsies were taken in 3/20 (15%) cases at a second surgical procedure. Areas of osteoclastic resorptive activity mixed with others of osteoblastic bone apposition, showed replacement with new bone. We conclude that cranial vault frozen allografts are a good alternative to autologous bone when the latter is absent or not present in sufficient amount. PMID:9265959

  13. [Cold autoimmune hemolytic anemia complicated with relapsed myelodysplastic syndrome after allogeneic hematopoietic cell transplantation].

    PubMed

    Okamura, Hiroshi; Nakane, Takahiko; Fujino, Keizo; Koh, Shiro; Yoshimura, Takuro; Nishimoto, Mitsutaka; Hayashi, Yoshiki; Koh, Hideo; Nakao, Yoshitaka; Nakamae, Hirohisa; Hino, Masayuki

    2015-04-01

    Myelodysplastic syndrome (MDS) is known to often be complicated by a range of autoimmune diseases. We herein present a case with MDS complicated by cold autoimmune hemolytic anemia (cold AIHA). The patient was a 51-year-old woman. She was diagnosed with MDS (refractory cytopenia with multilineage dysplasia) in May 2009. In January 2010, she underwent unrelated allogeneic bone marrow transplantation but was re-admitted in October 2010 for treatment of relapsed MDS. Despite daily transfusions of red blood cells, her anemia failed to improve. Her laboratory examinations showed a low haptoglobin level and elevation of indirect bilirubin and LDH. The direct Coombs test was positive at a low and at room temperature and cold agglutinin was negative. After confirming the diagnosis of cold AIHA, all transfusion fluids were warmed but her anemia still failed to improve. In addition to the warmed transfusion fluids, we administered corticosteroids, immunosuppressive agents and high-dose intravenous immunoglobulin infusions. This management strategy ameliorated the patient's hemolytic anemia. To our knowledge, MDS cases complicated by cold AIHA are rare. Our patient thus provides a valuable contribution to medical knowledge.

  14. Treosulfan, cyclophosphamide and antithymocyte globulin for allogeneic hematopoietic cell transplantation in acquired severe aplastic anemia.

    PubMed

    Giebel, Sebastian; Wojnar, Jerzy; Krawczyk-Kulis, Malgorzata; Markiewicz, Miroslaw; Wylezoł, Iwona; Seweryn, Marek; Holowiecka-Goral, Aleksandra; Holowiecki, Jerzy

    2006-01-01

    To reduce the risk of graft rejection after allogeneic hematopoietic cell transplantation (alloHCT) for patients with acquired severe aplastic anemia (SAA), we introduced an intensified preparative regimen consisting of treosulfan 10 g/m2/d on days -7, -6, cyclophosphamide 40 mg/kg/d on days -5, -4, -3, -2 and anti-thymocyte globulin 2 mg/kg/d on days -3, -2, -1. Six patients with the history of multiple transfusions were treated with alloHCT from either HLA-identical sibling (n=3) or an unrelated volunteer (n=3). Each, bone marrow and peripheral blood was used as a source of stem cells in three cases. All patients engrafted and achieved complete donor chimerism. None of the patients experienced severe organ toxicity. No severe acute graft-versus-host-disease (GVHD) was observed; two patients experienced extensive chronic GVHD. At the median follow-up of 14.5 (13-27) months all patients remained alive and disease-free. Our observation indicates that treosulfan + cyclophosphamide + antithymocyte globulin conditioning is well-tolerated and allows stable engraftment in acquired SAA. PMID:17494286

  15. Beneficial treatment with risedronate in long-term survivors after allogeneic stem cell transplantation for hematological malignancies.

    PubMed

    Tauchmanovà, L; Selleri, C; Esposito, M; Di Somma, C; Orio, F; Bifulco, G; Palomba, S; Lombardi, G; Rotoli, B; Colao, A

    2003-12-01

    In this prospective randomized study we evaluated the effect of risedronate, an aminobisphosphonate, on bone mass and turnover in patients who had undergone allogeneic stem cell transplant (SCT) for hematological malignancies. Thirty-four patients (18 females, 16 males, age 32+/-10 years) with bone mineral density (BMD) bone loss at the femoral neck in long-term survivors after allo-SCT.

  16. A Computational Model for Simulating Spaceflight Induced Bone Remodeling

    NASA Technical Reports Server (NTRS)

    Pennline, James A.; Mulugeta, Lealem

    2014-01-01

    An overview of an initial development of a model of bone loss due to skeletal unloading in weight bearing sites is presented. The skeletal site chosen for the initial application of the model is the femoral neck region because hip fractures can be debilitating to the overall performance health of astronauts. The paper begins with the motivation for developing such a model of the time course of change in bone in order to understand the mechanism of bone demineralization experienced by astronauts in microgravity, to quantify the health risk, and to establish countermeasures. Following this, a general description of a mathematical formulation of the process of bone remodeling is discussed. Equations governing the rate of change of mineralized bone volume fraction and active osteoclast and osteoblast are illustrated. Some of the physiology of bone remodeling, the theory of how imbalance in remodeling can cause bone loss, and how the model attempts to capture this is discussed. The results of a preliminary validation analysis that was carried out are presented. The analysis compares a set of simulation results against bone loss data from control subjects who participated in two different bed rest studies. Finally, the paper concludes with outlining the current limitations and caveats of the model, and planned future work to enhance the state of the model.

  17. Tissue engineering applications in the management of bone loss

    PubMed Central

    Carulli, Christian; Matassi, Fabrizio; Civinini, Roberto; Innocenti, Massimo

    2013-01-01

    Summary Several conditions in Orthopaedics and Traumatology are characterized by a bone loss. Bone auto- or allo-grafting was considered sufficient to fullfill the defects decades ago; however, large bone defects were challenging for the Surgeons, particularly in case of necessity of structural and biological properties. Bioindusrty proposed over the years synthetic biomaterials, as Demineralized Bone Matrix, bioactive surfaces for implant coponents, and recently recombinant Bone Morphogenetic Proteins. At the same time, the concept of the “biological chamber” and “diamond concept” allowed the scientific community to consider the need of a more complex interaction between scaffolds (matrix), cells (mesenchymal cells), and signaling (growth factors) in order to induce bone regeneration and also to fill small or large bone defects. A brief overview is made on the processes of a physiologic bone metabolism (induction, conduction, osteogenesis), on the latest therapeutical procedures, based on the use of autologous growth factors and cells, and the recent prosthetic or synthetic scaffolds, and the common clinical conditions that may beneficiate of these modern approaches. PMID:23858306

  18. Raman spectroscopy for monitoring of organic and mineral structure of bone grafts

    NASA Astrophysics Data System (ADS)

    Timchenko, Elena V.; Timchenko, Pavel E.; Volova, Larisa T.; Ponomareva, Julia V.; Taskina, Larisa A.; Pershutkina, Svetlana V.

    2014-09-01

    The results of experimental studies of donor bone samples (rat, rabbit and human) with varying degrees of mineralisation by Raman spectroscopy were presented. Raman spectra were obtained for the Raman bands 950-962 (РО4)3-, 1065-1070 (СО3)2- and 1665 cm-1 (Amide I). In demineralized bone a sharp decline (to 98 %) in the range of 950-962 cm-1 (РО4)3- and 1065 - 1070 cm-1 was observed. This decrease was accompanied by the emergence of the 1079-1090 cm-1 band corresponding to the hydrated state СО3 2-.

  19. Magnetic resonance imaging appearance of scurvy with gelatinous bone marrow transformation.

    PubMed

    Brennan, Christopher M; Atkins, Kristen A; Druzgal, Colleen H; Gaskin, Cree M

    2012-03-01

    Scurvy is a lethal but treatable disease that is rare in industrialized countries. Caused by vitamin C deficiency, it is most prevalent in persons of low socioeconomic status and smokers. Low levels of circulating vitamin C result in poor collagen fiber formation that, in turn, leads to demineralized bones, microfractures, and poor healing. Here we report a case of scurvy in a 5-year-old boy with normal radiographs in whom initial concern for leukemia based upon magnetic resonance imaging and clinical presentation led to a bone marrow biopsy revealing gelatinous transformation.

  20. Clinicopathological analysis of allogeneic hematopoietic stem cell transplantation-related membranous glomerulonephritis.

    PubMed

    Hiramatsu, Rikako; Ubara, Yoshifumi; Sawa, Naoki; Hasegawa, Eiko; Kawada, Masahiro; Imafuku, Aya; Sumida, Keiichi; Mise, Koki; Yamanouchi, Masayuki; Ueno, Toshiharu; Sekine, Akinari; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Wake, Atsushi; Taniguchi, Shuichi

    2016-04-01

    Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation. MGN was diagnosed in 5 patients after UCBT (versus none after bone marrow transplantation) and occurred concomitantly with chronic graft-versus-host disease after cessation of immunosuppression. Light microscopy did not show any definite spikes or bubbling of the glomerular basement membrane (GBM) in all 5 patients. In 1 patient (case 5), endocapillary proliferative lesions with fibrin-like deposits were noted in addition to MGN findings. Immunofluorescence demonstrated granular deposits of immunoglobulin G (IgG; IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), whereas case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. Electron microscopy revealed electron-dense deposits in the subepithelial space of the GBM in cases 1-4. In case 5, electron-dense deposits were present in the mesangium and the subendothelial space of the GBM, as well as in the subepithelial space. After treatment with immunosuppressants (prednisolone and/or cyclosporin) or angiotensin-converting enzyme inhibitors, complete remission with disappearance of proteinuria was achieved 12.2 months in all 5 patients, but nephrotic-range proteinuria relapsed in 2 patients during follow-up. Serum anti-PLA2R autoantibody was negative in 3 patients. HSCT-related MGN only occurred after UCBT. We believe that there were 2 morphologic patterns: early MGN and membranoproliferative pattern glomerulonephritis.

  1. Stromal cells from term fetal membrane are highly suppressive in allogeneic settings in vitro.

    PubMed

    Karlsson, H; Erkers, T; Nava, S; Ruhm, S; Westgren, M; Ringdén, O

    2012-03-01

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) have immunosuppressive properties and have been used to treat steroid-refractory acute graft-versus-host disease (GVHD) in stem cell transplant patients. Cells with similar capacities can also be found in term placental tissue. We have isolated stromal cells from term fetal membrane (FMSCs), umbilical cords (UCSCs) and placental villi (PVSCs) as well as from bone marrow and compared their immunoregulatory capacity in allogeneic settings. We found that FMSCs and UCSCs suppressed proliferation significantly in mixed lymphocyte reactions (MLRs), whereas PVSCs showed inconsistent suppressive effects. When added to MLR cultures, FMSCs suppressed the production of interferon (IFN)-γ and interleukin (IL)-17, whereas UCSCs and PVSCs promoted the production of IL-17 instead. Secretion of IL-10 was increased after addition of FMSCs and UCSCs. In this setting, BM-MSCs had no significant effect on secretion of IFN-γ, IL-17 or IL-10 in MLR cultures. When analysing the expression of adhesion markers, we noted that FMSCs expressed the highest levels of CD29 (β1), CD49d (α4) and CD54 (ICAM-1) compared to the other types of stromal cells. Thus, our data indicate that stromal cells isolated from term fetal membrane have great immunosuppressive capacity in terms of proliferation and production of proinflammatory cytokines from alloreactive T cells, and also promote anti-inflammatory IL-10. They express high levels of integrins that may be of importance in homing to inflamed tissues. Fetal membrane may provide a valuable source of cells with immunosuppressive properties and could possibly be used for treatment of acute GVHD and other inflammatory disorders.

  2. Histologic Evaluation of Bone Healing Capacity Following Application of Inorganic Bovine Bone and a New Allograft Material in Rabbit Calvaria

    PubMed Central

    Paknejad, Mojgan; Rokn, AmirReza; Rouzmeh, Nina; Heidari, Mohadeseh; Titidej, Azadehzeinab; Kharazifard, Mohammad Javad; Mehrfard, Ali

    2015-01-01

    Objectives: Considering the importance of bone augmentation prior to implant placement in order to obtain adequate bone quality and quantity, many studies have been conducted to evaluate different techniques and materials regarding new bone formation. In this study, we investigated the bone healing capacity of two different materials deproteinized bovine bone mineral (DBBM with the trade name of Bio-Oss) and demineralized freeze-dried bone allograft (DFDBA with the trade name of DynaGraft). Materials and Methods: This randomized blinded prospective study was conducted on twelve New Zealand white rabbits. Three cranial defects with an equal diameter were created on their calvarium. Subsequently, they were distributed into three groups: 1. The control group without any treatment; 2. The Bio-Oss group; 3. The DynaGraft group. After 30 days, the animals were sacrificed for histologic and histomorphometric analysis. Results: Substantial new bone formation was observed in both groups. DynaGraft: 56/1 % ± 15/1 and Bio-Oss: 53/55 % ± 13/5 compared to the control group: 28/6 % ± 11/2. All groups showed slight inflammation and a small amount of residual biomaterial was observed. Conclusion: Considerable new bone formation was demonstrated in both DynaGraft and Bio-Oss groups in comparison with the control group. Both materials are considered biocompatible regarding the negligible foreign body reaction. PMID:26005452

  3. Scientific basis for the study of demineralization of highly mineralized water for use in public water supply systems.

    PubMed Central

    Sidorenko, G I; Rakhmanin, Y A

    1979-01-01

    New criteria (full physiological value and preservation of the properties of drinking water) are scientifically substantiated. Also discussed are indices (minimal admissible and optimal levels of basic water mineralization and calcium content, standards of microelements such as boron and bromine content, content of individual groups of microorganisms, water temperature) for evaluating the quality of demineralized water obtained from brackish and briny water (including water from the sea and ocean) by various methods which are designed for public water supply systems. Research results served as the scientific hygiene basis for the development of a new technology of obtaining drinking water. The necessity for developing a special quality standard for demineralized drinking water is shown. PMID:446445

  4. Bone morphogenetic proteins and their antagonists: current and emerging clinical uses

    PubMed Central

    Ali, Imran H A; Brazil, Derek P

    2014-01-01

    Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily of secreted cysteine knot proteins that includes TGFβ1, nodal, activins and inhibins. BMPs were first discovered by Urist in the 1960s when he showed that implantation of demineralized bone into intramuscular tissue of rabbits induced bone and cartilage formation. Since this seminal discovery, BMPs have also been shown to play key roles in several other biological processes, including limb, kidney, skin, hair and neuronal development, as well as maintaining vascular homeostasis. The multifunctional effects of BMPs make them attractive targets for the treatment of several pathologies, including bone disorders, kidney and lung fibrosis, and cancer. This review will summarize current knowledge on the BMP signalling pathway and critically evaluate the potential of recombinant BMPs as pharmacological agents for the treatment of bone repair and tissue fibrosis in patients. PMID:24758361

  5. Bone scanning.

    PubMed

    Greenfield, L D; Bennett, L R

    1975-03-01

    Scanning is based on the uptake of a nuclide by the crystal lattice of bone and is related to bone blood flow. Cancer cells do not take up the tracer. Normally, the scan visualizes the highly vascular bones. Scans are useful and are indicated in metastatic bone disease, primary bone tumors, hematologic malignancies and some non-neoplastic diseases. The scan is more sensitive than x-ray in the detection of malignant diseases of the skeleton. PMID:1054210

  6. Host-derived neoangiogenesis with short-term immunosuppression allows incorporation and remodeling of vascularized diaphyseal allogeneic rabbit femur transplants.

    PubMed

    Giessler, Goetz A; Zobitz, Mark; Friedrich, Patricia F; Bishop, Allen T

    2009-06-01

    The purpose of this study was to demonstrate that living bone allotransplants can incorporate, remodel, and maintain mechanical properties without long-term immunosuppression in a fashion comparable to living autotransplants. For this, viability is maintained by repair of nutrient vessels and neovascularization from implanted host-derived vasculature. Microsurgically revascularized femoral diaphysis allotransplants were transferred from young male New-Zealand-White (NZW) into 4 groups of male Dutch-Belted (DB) rabbits. Short-term immunosuppression by tacrolimus (IS, groups 4 and 5) and host-derived neovascularization (NV) from implanted fascial flaps was used to maintain viability (groups 3 and 5) as independent variables. Group 2 received neither IS nor NV. Vascularized pedicled autotransplants were orthotopically transplanted in group 1. After 16 weeks, transplants were evaluated using radiologic, histologic, biomechanical, and histomorphometric parameters. Vascularized bone allotransplants treated with both short-term IS and host-derived NV (group 5) healed in a fashion similar to pedicled autotransplants (group 1). Their radiographic scores were higher than other groups. Groups with patent fascial flaps (3 and 5) showed significantly greater neoangiogenesis than ligated controls (2 and 4). Tacrolimus administration did not affect neoangiogenesis. Elastic modulus and ultimate stress were significantly greater in autogenous bone than in allotransplanted femora. Biomechanical properties were not significantly different among allotransplants. Bone turnover was decreased with IS, but increased with NV by the implanted fascial flaps. Living allogeneic femoral allotransplants treated with short-term IS and host-derived neoangiogenesis can lead to stable transplant incorporation in this rabbit model. The combination of both factors optimizes bone healing. Transplant mineralization is improved with neoangiogenesis but diminished with IS.

  7. Does ozone enhance the remineralizing potential of nanohydroxyapatite on artificially demineralized enamel? A laser induced fluorescence study

    NASA Astrophysics Data System (ADS)

    Srinivasan, Samuelraj; Prabhu, Vijendra; Chandra, Subhash; Koshy, Shalini; Acharya, Shashidhar; Mahato, Krishna K.

    2014-02-01

    The present era of minimal invasive dentistry emphasizes the early detection and remineralization of initial enamel caries. Ozone has been shown to reverse the initial demineralization before the integrity of the enamel surface is lost. Nano-hydroxyapatite is a proven remineralizing agent for early enamel caries. In the present study, the effect of ozone in enhancing the remineralizing potential of nano-hydroxyapatite on artificially demineralized enamel was investigated using laser induced fluorescence. Thirty five sound human premolars were collected from healthy subjects undergoing orthodontic treatment. Fluorescence was recorded by exciting the mesial surfaces using 325 nm He-Cd laser with 2 mW power. Tooth specimens were subjected to demineralization to create initial enamel caries. Following which the specimens were divided into three groups, i.e ozone (ozonated water for 2 min), without ozone and artificial saliva. Remineralization regimen was followed for 3 weeks. The fluorescence spectra of the specimens were recorded from all the three experimental groups at baseline, after demineralization and remineralization. The average spectrum for each experimental group was used for statistical analysis. Fluorescence intensities of Ozone treated specimens following remineralization were higher than that of artificial saliva, and this difference was found to be statistically significant (P<0.0001). In a nutshell, ozone enhanced the remineralizing potential of nanohydroxyapatite, and laser induced fluorescence was found to be effective in assessing the surface mineral changes in enamel. Ozone can be considered an effective agent in reversing the initial enamel caries there by preventing the tooth from entering into the repetitive restorative cycle.

  8. Effect of Nd:YAG laser combined with fluoride on the prevention of primary tooth enamel demineralization.

    PubMed

    Azevedo, Danielle Torres; Faraoni-Romano, Juliana Jendiroba; Derceli, Juliana Dos Reis; Palma-Dibb, Regina Guenka

    2012-01-01

    Most studies dealing with the caries preventive action of Nd:YAG laser have been done in permanent teeth and studies on primary teeth are still lacking. The aim of this study was to evaluate in vitro the effect of Nd:YAG laser combined or not with fluoride sources on the acid resistance of primary tooth enamel after artificial caries induction by assessing longitudinal microhardness and demineralization depth. Sixty enamel blocks obtained from the buccal/lingual surface of exfoliated human primary molars were coated with nail polish/wax, leaving only a 9 mm² area exposed on the outer enamel surface, and randomly assigned to 6 groups (n=10) according to the type of treatment: C-control (no treatment); APF: 1.23% acidulated phosphate fluoride gel; FV: 5% fluoride varnish; L: Nd:YAG laser 0.5 W/10 Hz in contact mode; APFL: fluoride gel + laser; FVL: fluoride varnish + laser. After treatment, the specimens were subjected to a des-remineralization cycle for induction of artificial caries lesions. Longitudinal microhardness data (%LMC) were analyzed by the Kruskal-Wallis test and demineralization depth data were analyzed by oneway ANOVA and Fisher's LSD test (á=0.05). APFL and APF groups presented the lowest percentage of microhardness change (p<0.05). Demineralization depth was smaller in all treated groups compared with the untreated control. In conclusion, Nd:YAG laser combined or not with fluoride gel/varnish was not more effective than fluoride alone to prevent enamel demineralization within the experimental period. PMID:22666766

  9. Effect of high-fructose corn syrup on Streptococcus mutans virulence gene expression and on tooth demineralization.

    PubMed

    Sun, Minmin; Kang, Qiongyi; Li, Tingting; Huang, Lili; Jiang, Yuntao; Xia, Wenwei

    2014-06-01

    High-fructose corn syrup-55 (HFCS-55) has been widely welcomed in recent years as a substitute for sucrose on the basis of its favourable properties and price. The objective of this study was to determine the influence of HFCS-55 on the expression of Streptococcus mutans UA159 virulence genes and on tooth demineralization. Real-time reverse-transcription PCR (real-time RT-PCR) and microhardness evaluations were performed to examine gene expression and enamel demineralization, respectively, after treatment with HFCS-55 and/or sucrose. Significant up-regulation of glucosyltransferase B (gtfB) by HFCS-55 was found. A mixture of HFCS-55 and sucrose could positively enhance expression of glucan-binding protein (gbp) genes. Regarding acidogenicity, expression of the lactate dehydrogenase (ldh) gene was unaffected by HFCS-55. A notable finding in this study was that 5% HFCS-55 significantly enhanced expression of the intracellular response gene of the two-component VicRK signal transduction system (vicR). Demineralization testing showed that the microhardness of teeth decreased by a greater extent in response to HFCS-55 than in response to sucrose. The results indicate that HFCS-55 can enhance S. mutans biofilm formation indirectly in the presence of sucrose and that HFCS-55 has a more acidogenic potential than does sucrose. Summing up the real-time PCR and demineralization results, HFCS-55 appears to be no less cariogenic than sucrose in vitro - at least, not under the conditions of our experiments. PMID:24813075

  10. Effects of a cloned cell line with NK activity on bone marrow transplants, tumour development and metastasis in vivo

    NASA Astrophysics Data System (ADS)

    Warner, John F.; Dennert, Gunther

    1982-11-01

    Natural killer (NK) cells cloned in vitro have been transferred into NK-deficient hosts. These cells have been shown to have a role in the rejection of allogeneic bone marrow grafts, resistance to both radiation-induced thymic leukaemia and challenge with melanoma tumour cells. It appears that NK cells have an important role in immune surveillance.

  11. Phase I study of the safety and pharmacokinetics of plerixafor in children undergoing a second allogeneic hematopoietic stem cell transplantation for relapsed or refractory leukemia

    PubMed Central

    Srinivasan, Ashok; Panetta, John C.; Cross, Shane; Pillai, Asha; Triplett, Brandon M.; Shook, Dave R.; Dallas, Mari H.; Hartford, Christine; Sunkara, Anusha; Kang, Guolian; Jacobsen, Jeffrey; Choi, John; Leung, Wing

    2015-01-01

    The safety, pharmacokinetics and biological effect of plerixafor in children as part of a conditioning regimen for chemo-sensitization in allogeneic hematopoietic stem cell transplantation (HSCT) have not been studied. This is a phase I study of plerixafor designed to evaluate its tolerability at dose of 0.24 mg/kg given intravenously on day -4 (level 1), day -4, and day -3 (level 2), or day -4, -3, and day -2 (level 3) in combination with fludarabine, thiotepa, melphalan, and rabbit anti-thymocytic globulin for a second allogeneic HSCT in children with refractory or relapsed leukemia. Immunophenotype analysis was performed on blood and bone marrow prior to and after plerixafor administration. Twelve patients were enrolled. Plerixafor at all 3 levels was well tolerated without dose-limiting toxicity. Transient gastrointestinal side effects of National Cancer Institute grade 1 or 2 in severity were the most common adverse events. The area under the concentration-time curve increased proportionally to the dose level. Plerixafor clearance was higher in males, and increased linearly with body weight, and glomerular filtration rate. The clearance decreased and the elimination half-life increased significantly from dose level 1 to 3 (P < 0.001). Biologically, the proportion of CXCR4-positive blasts and lymphocytes both in the bone marrow and peripheral blood, increased after plerixafor administration. PMID:24769325

  12. Transmission of an expanding donor-derived del(20q) clone through allogeneic hematopoietic stem cell transplantation without the development of a hematologic neoplasm.

    PubMed

    Aikawa, Vania; Porter, David; Luskin, Marlise R; Bagg, Adam; Morrissette, Jennifer J D

    2015-12-01

    Donor cell leukemia is a rare complication of allogeneic hematopoietic stem cell transplantation (HSCT), which may result from the development of a new malignancy in previously healthy donor cells after transplant into the recipient, or it may derive from the transmission of an occult leukemia from donor to recipient. We report a case of donor derived 20q11.2 deletion in a male patient who received an allogeneic HSCT from his HLA-identical sister for the treatment of his chronic lymphocytic leukemia. Bone marrow cells from the donor were found to contain the 20q deletion that expanded over time, but which was absent in her peripheral blood cells. Although cases of donor cell leukemia after HSCT have been reported, in this case there has been no evidence of an associated hematologic neoplasm in either the donor or recipient. Pre-transplant donor bone marrow evaluations are not practical or warranted, however the finding of new cytogenetic abnormalities after transplant mandates a thorough evaluation of the donor.

  13. Evaluation of enamel surface modification using PS-OCT after laser treatment to increase resistance to demineralization

    PubMed Central

    Kim, Jin Wan; Chan, Kenneth H.; Fried, Daniel

    2016-01-01

    At laser intensities below ablation, carbonated hydroxyapatite in enamel is converted into a purer phase hydroxyapatite with increased acid resistance. Previous studies suggested the possibility of achieving the conversion without surface modification. This study attempts to evaluate the thresholds for the modification without additional changes in physical and optical properties of the enamel. Bovine specimens were irradiated using an RF-excited CO2 laser operating at 9.4-µm with a pulse duration of 26-µs, pulse repetition rates of 100–1000 Hz, with a Gaussian spatial beam profile - 1.4 mm in diameter. After laser treatment, the samples were subjected to acid demineralization for 48 hours to simulate acidic intraoral conditions of a caries attack. The resulting demineralization and erosion were assessed using polarization sensitive OCT (PS-OCT) and 3D digital microscopy. The images from digital microscopy demonstrated a clear delineation between laser protected zones without visual changes and zones with higher levels of demineralization and erosion. Distinct changes in the surface morphology were found within the laser treated area in accordance with the Gaussian spatial beam profile. There was significant protection from the laser in areas that were not visually altered. PMID:27006523

  14. Evaluation of enamel surface modification using PS-OCT after laser treatment to increase resistance to demineralization

    NASA Astrophysics Data System (ADS)

    Kim, Jin Wan; Chan, Kenneth H.; Fried, Daniel

    2016-02-01

    At laser intensities below ablation, carbonated hydroxyapatite in enamel is converted into a purer phase hydroxyapatite with increased acid resistance. Previous studies suggested the possibility of achieving the conversion without surface modification. This study attempts to evaluate the thresholds for the modification without additional changes in physical and optical properties of the enamel. Bovine specimens were irradiated using an RF-excited CO2 laser operating at 9.4-μm with a pulse duration of 26- μs, pulse repetition rates of 100-1000 Hz, with a Gaussian spatial beam profile - 1.4 mm in diameter. After laser treatment, the samples were subjected to acid demineralization for 48 hours to simulate acidic intraoral conditions of a caries attack. The resulting demineralization and erosion were assessed using polarization sensitive OCT (PS-OCT) and 3D digital microscopy. The images from digital microscopy demonstrated a clear delineation between laser protected zones without visual changes and zones with higher levels of demineralization and erosion. Distinct changes in the surface morphology were found within the laser treated area in accordance with the Gaussian spatial beam profile. There was significant protection from the laser in areas that were not visually altered.

  15. Effect of dentifrice containing fluoride and/or baking soda on enamel demineralization/remineralization: an in situ study.

    PubMed

    Cury, J A; Hashizume, L N; Del Bel Cury, A A; Tabchoury, C P

    2001-01-01

    The additive effect of baking soda on the anticariogenic effect of fluoride dentifrice is not well established. To evaluate it, a crossover in situ study was done in three phases of 28 days. Volunteers, using acrylic palatal appliances containing four human enamel blocks, two sound (to evaluate demineralization) and two with artificial caries lesions (to evaluate remineralization), took part in this study. During each phase, 10% sucrose solution was dripped (3 times a day) only onto the sound blocks. After 10 min, a slurry of placebo, fluoride (F) or fluoride and baking soda (F+NaHCO(3)) dentifrice was dripped onto all enamel blocks. The results showed a higher F concentration in dental plaque formed during treatment with F+NaHCO(3) than placebo (p<0.05), but the difference related to F dentifrice was not significant. The enamel demineralization was lower, and remineralization was greater, after treatment with F+NaHCO(3) than placebo (p<0.05), but the difference related to F dentifrice was not significant. The data suggest that baking soda neither improves nor impairs the effect of F dentifrice on reduction of demineralization and enhancement of remineralization of enamel. PMID:11275669

  16. Effect of dentifrice containing fluoride and/or baking soda on enamel demineralization/remineralization: an in situ study.

    PubMed

    Cury, J A; Hashizume, L N; Del Bel Cury, A A; Tabchoury, C P

    2001-01-01

    The additive effect of baking soda on the anticariogenic effect of fluoride dentifrice is not well established. To evaluate it, a crossover in situ study was done in three phases of 28 days. Volunteers, using acrylic palatal appliances containing four human enamel blocks, two sound (to evaluate demineralization) and two with artificial caries lesions (to evaluate remineralization), took part in this study. During each phase, 10% sucrose solution was dripped (3 times a day) only onto the sound blocks. After 10 min, a slurry of placebo, fluoride (F) or fluoride and baking soda (F+NaHCO(3)) dentifrice was dripped onto all enamel blocks. The results showed a higher F concentration in dental plaque formed during treatment with F+NaHCO(3) than placebo (p<0.05), but the difference related to F dentifrice was not significant. The enamel demineralization was lower, and remineralization was greater, after treatment with F+NaHCO(3) than placebo (p<0.05), but the difference related to F dentifrice was not significant. The data suggest that baking soda neither improves nor impairs the effect of F dentifrice on reduction of demineralization and enhancement of remineralization of enamel.

  17. Remineralized Bone Matrix (RBM) as a Scaffold for Bone Tissue Engineering

    PubMed Central

    Soicher, Matthew A.; Christiansen, Blaine A.; Stover, Susan M.; Leach, J. Kent; Yellowley, Clare E.; Griffiths, Leigh G.; Fyhrie, David P.

    2014-01-01

    There is a need for improved biomaterials for use in treating non-healing bone defects. A number of natural and synthetic biomaterials have been used for the regeneration of bone tissue with mixed results. One approach is to modify native tissue via decellularization or other treatment for use as natural scaffolding for tissue repair. In this study, our goal was to improve on our previously published alternating solution immersion (ASI) method to fabricate a robust, biocompatible, and mechanically competent biomaterial from natural demineralized bone matrix (DBM). The improved method includes an antigen removal (AR) treatment step which improves mineralization and stiffness while removing unwanted proteins. The chemistry of the mineral in the remineralized bone matrix (RBM) was consistent with dicalcium phosphate dihydrate (brushite), a material used clinically in bone healing applications. Mass spectrometry identified proteins removed from the matrix with AR treatment to include α-2 HS-glycoprotein and osteopontin, non-collagenous proteins (NCPs) and known inhibitors of biomineralization. Additionally, the RBM supported the survival, proliferation, and differentiation of human mesenchymal stromal cells (MSCs) in vitro as well or better than other widely used biomaterials including DBM and PLG scaffolds. DNA content increased more than 10-fold on RBM compared to DBM and PLG; likewise, osteogenic gene expression was significantly increased after 1 and 2 weeks. We demonstrated that ASI remineralization has the capacity to fabricate mechanically stiff and biocompatible RBM, a suitable biomaterial for cell culture applications. PMID:24616346

  18. Characterization of Bone Marrow Mononuclear Cells on Biomaterials for Bone Tissue Engineering In Vitro

    PubMed Central

    Verboket, René; Kontradowitz, Kerstin; Oppermann, Elsie; Brune, Jan C.; Nau, Christoph; Meier, Simon; Bonig, Halvard; Marzi, Ingo; Seebach, Caroline

    2015-01-01

    Bone marrow mononuclear cells (BMCs) are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on bio