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1.
Composite tissue allografts (CTAs) are currently accepted in the clinic; however, long-term immunosuppression is still needed for allograft survival. The presence of donor-specific chimerism may induce tolerance. Thirty-six vascularized bone marrow transplantation (VBMT) allotransplantation were performed across MHC barrier under short-term protocol of 7-day alphabeta-TCRmAb and Cyclosporin A therapy to determine the efficacy of VBMT alone and VBMT augmented with donor bone marrow transplantation (BMT) in chimerism induction. Flow cytometry analysis revealed that VBMT supported with donor BMT directly into the bone resulted in chimerism augmentation and maintenance compared to VBMT. In vivo and in vitro tolerance testing showed prolonged survival of donor skin graft up to 35 days and moderate reactivity in MLR assay that suggests only tolerance induction. Transplantation of vascularized bone without chronic immunosuppression provides a substantial source of bone marrow cells, leading to the development of stable donor-specific chimerism. 相似文献
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目的通过对山羊股骨、髂骨、胸骨、肋骨4个较为常见的血管化骨髓移植供区部位相关结构的测量观察,从移植手术的角度,分析其解剖特点,为下一步建立山羊血管化骨髓移植模型提供一定的解剖依据。方法取6只(共12侧)体质量相当的山羊做活体解剖研究。观测4个供区血液供应情况,并对比4种移植物体质量、体积、骨髓干细胞密度等因素。结果髂骨可见主要滋养血管为髂内动脉及其分支,另外紧贴骨面的臀部肌肉也会有细小动脉进入骨膜,髂内血管为较理想的血管蒂;股骨的主要滋养动脉有3条:股深动脉、旋股外侧动脉及膝降动脉,取髂外血管为血管蒂;双侧胸廓内动脉及伴行静脉为胸骨的主要滋养血管,双侧胸廓内动静脉的近端可作为游离血管蒂;肋骨以第7肋为例,其肋间后动脉及其伴行静脉为主要滋养血管,可以取到一定长度的游离血管蒂。结论山羊的髂骨及股骨是较为理想的血管化骨髓移植术供区,其游离血管蒂长度及其动静脉外径均可满足异体移植术的需求。 相似文献
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目的 构建一种简单可靠的带血管的骨髓移植模型.方法 将供体带血管蒂的股骨通过显微血管吻合的方式移植到受体腹股沟区,20只Lewis近交系大鼠随机分3组:同基因移植组Lewis→Lewis;排斥组Lewis→BN;免疫抑制组Lewis→BN,术后给予环孢素A.通过大体和病理学检查观察各组移植物存活情况,流式细胞计数监测外周血嵌合水平.结果 术后30 d,同基因移植组股骨存活良好,骨髓苏木素-伊红(HE)染色与正常骨髓无异,而排斥组第7天即发生显著的排斥反应,骨髓细胞明显减少、坏死,外周血嵌合水平几乎为0;和同系移植组一样,免疫抑制组术后30 d移植物存活良好,术后1、2、3、4周外周血中可检测到供体特异性嵌合,嵌合水平分别为(4.7±2.0)%、(2.2±1.2)%、(1.8±0.9)%、(1.5±0.3)%.结论 带血管蒂的股骨移植是一种简便可靠的骨髓移植模型,可作为一种新的骨髓移植方法诱导免疫耐受. 相似文献
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Cohen M Mohanakumar T Mackinnon SE Tung TH 《Journal of reconstructive microsurgery》2006,22(5):375-384
This study used quantitative PCR in the murine model to compare the ability of a limb allograft vs. a comparable dose of marrow suspension to induce chimerism. Female C57Bl/6 mice received a vascularized hindlimb allograft, a comparable dose of 5 x 10 (6) donor bone marrow cells, or a standard dose (20 x 10 (6)) of marrow suspension from male Balb/c donors. All recipients were treated with a regimen based on CD40 costimulation blockade and T cell depletion. Y chromosome-specific quantitative PCR was used to measure chimerism. Most recipients of limb allografts demonstrated low levels of chimerism after 1 week (3/4) and 1 month (3/4). Most recipients of 5 x 10 (6) marrow cells had low levels of chimerism at 1 week (4/6) and only 1/5 after 1 month. All recipients of 20 x 10 (6) cells except one demonstrated either low or high levels of chimerism after 1 week (5/5) and 1 month (5/6). The marrow component of a limb allograft is thus more effective at inducing microchimerism compared to a comparable dose of bone marrow suspension. 相似文献
5.
In this study, we introduce a new model for vascularized skin and bone marrow transplantation. Twenty-five Lewis (RT1(1)) rats were studied. Anatomic dissection studies were performed in 5 animals. In the experimental group, 10 isograft transplantations were performed between Lewis rats. Combined groin skin and femoral bone flaps were transplanted based on the femoral artery and vein. Transplants were evaluated on a daily basis. All flaps survived without problems over 100 days posttransplant. The skin component remained pink and pliable, and grew new hair. Histological examination of the femoral bone (except the femoral head) revealed active hematopoiesis with a viable compact and cancellous bone components on day 100 posttransplant. This model can be applied to tolerance induction studies across the major Histocompatibility (MHC) barrier, where bone will serve as donor of stem and progenitor cells, and the skin flap will serve as a monitor of graft rejection. 相似文献
6.
Comparative analysis of immunological reconstitution induced by vascularized bone marrow versus bone marrow cell transplantation 总被引:1,自引:0,他引:1
Abstract We have reported previously that vascularized bone marrow transplantation (VBMT) in an orthotopic hind limb graft brings about complete repopulation of bone marrow cavities in lethally irradiated syngeneic recipients within 10 days. Intravenous infusion of an equivalent volume of bone marrow cell suspension was evidently less effective. The purpose of this study was to investigate the reconstitution of immunocompetent compartments of lethally irradiated syngeneic rats after VBMT. Lewis rat hind limbs were transplanted orthotopically into irradiated recipients. Ten days after irradiation and bone marrow transplantation, bone marrow, mesenteric lymph nodes, and sera from rats were harvested. Mesenteric lymph node lymphocytes were analyzed. The responsiveness fomesenteric lymph node lymphocytes (MLNL) to mitogens and cell proliferation in the presence of sera and bone marrow cell (BMC) culture supernatants were measured. Our studies have shown that vascularized bone marrow transplantation brings about rapid replenishment of lymphoid organs of lethally irradiated syngeneic recipients. The re-populating subsets are fully responsive to mitogens. Sera from reconstituting rats had no effect on the proliferation of mature lymphocytes. Intravenous infusion of a number of BMC in suspension equivalent to that grafted in hind limb transplant was less efficient in reconstitution of lymphoid tissue. 相似文献
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We present a new model of vascularized bone marrow transplantation-bilateral vascularized femoral bone (BVFB) isograft transplant based on abdominal aorta and inferior vena cava. A total of 7 BVFB isograft transplants were performed between Lewis (RT1) rats. In the donor, both femoral bones were harvested based on the abdominal aorta and inferior vena cava. In the recipient, the harvested isograft transplants were transferred into the inguinal region (in 3 animals) and into the abdominal cavity (in 4 animals). The mean operation time was 3 hours and 35 minutes. The mean warm ischemic time was 35 minutes. The vascular pedicles of the transplants that were transferred into the inguinal region were thrombosed at day 7 posttransplantation. The vascular pedicles of transplants into the abdominal cavity were patent and the bones were viable during the follow-up period of 63 days posttransplant. We have confirmed the feasibility of BVFB transplantation based on abdominal aorta and inferior vena cava. 相似文献
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Absence of graft-versus-host disease in the isolated vascularized bone marrow transplant 总被引:1,自引:0,他引:1
Tai CY Strande LF Eydelman R Sheng X VanTran JL Matthews MS Hewitt CW 《Transplantation》2004,77(2):316-319
An isolated vascularized bone marrow transplant (iVBMT) model was developed to study the contribution of the bone marrow component in a composite tissue allograft. We hypothesized that the iVBMT would be functional and cause graft-versus-host disease (GVHD) in a fraction of the recipients. Lewis iVBMT grafts were transplanted to Lewis-Brown Norway recipients. Animals were sacrificed at various times from 1 to 14 weeks. Polymerase chain reaction for microchimerism was performed on the host's marrow. No animals exhibited signs of GVHD at death. Histologic examination of the grafts showed a normal mix of hematopoietic and fatty elements and appeared to be functional. Tissues usually affected-tongue, ear, liver, and gut-also showed no evidence of disease. Polymerase chain reaction demonstrated microchimerism in both groups. These findings suggest that the vascularized bone marrow within a composite tissue allograft is not the component that causes GVHD; rather, it may serve an immunomodulatory function for tolerance induction. 相似文献
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Rat limb allograft recipients represent surgically induced, immediately vascularized bone marrow transplant (VBMT) chimeras. The majority of these chimeras undergo tolerance while a minority develop graft versus host disease (GVHD). T-cell chimerism and associated mechanisms of cellular immune nonresponsiveness were investigated in tolerant VBMT chimeras. A strong correlation (p < 0.01) was observed between the clinical onset of GVHD and levels of donor T-cell chimerism approximating or greater than 50%. However, stable mixed chimerism was associated with tolerance. In conclusion, three major sequential mechanisms of immune nonresponsiveness were elucidated in tolerant VBMT chimeras over time and included development of nonspecific suppressor cells (which potentially represent natural suppressor cells), maturation of antigen-specific suppressor cell circuits, and eventually putative clonal inactivation. 相似文献
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Transplantation of T-lymphocyte-depleted bone marrow between HLA-mismatched individuals 总被引:1,自引:0,他引:1
W E Spruce R McMillan W Miller R Fox D Carson D B Schwartz G A Hartman L W Renshaw E Beutler 《Transplantation》1983,36(4):369-372
Four patients with acute leukemia received transplants from HLA-mismatched, related donors. Marrow cells that had been depleted of T lymphocytes using a monoclonal anti-T-lymphocyte antibody and rabbit complement were used. In vitro studies showed that 80-97% of the mature T lymphocytes were removed using this procedure. Infusion of the treated marrow was accomplished without complications, and engraftment occurred in each case. Graft-versus-host disease occurred in 3 of the 4 patients. These results show that additional manipulations of the marrow will be required to allow complete T lymphocyte removal from the marrow before the feasibility of this approach in HLA-mismatched patients can be determined. 相似文献
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Tai CY France MA Strande LF Eydelman R Sheng X Matthews MS Dalsey R Hewitt CW 《Transplantation》2003,75(9):1591-1593
An isolated vascularized bone marrow transplant (iVBMT) model was previously developed in the rat to specifically study the role of bone marrow and its environment in a composite tissue allotransplant. An extraperitoneal model was successfully created to avoid laparotomy and cross-clamping of the great vessels. The extraperitoneal iVBMT model consisted of a left donor femur that was harvested with its nutrient vessels, anastomosed to the right femoral vessels in a syngeneic host, and then placed subcutaneously in the abdominal wall. At explant, the graft vessels were grossly patent, and histology of the graft bones showed a viable marrow compartment. Polymerase chain reaction demonstrated peripheral chimerism in the recipients. This model is technically simple with minimal morbidity in the recipient animals. By using the iVBMT, future studies across semiallogeneic and allogeneic barriers will help define the role of the bone marrow compartment in composite tissue allotransplants to potentially induce immune tolerance. 相似文献
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目的 研究兔骨髓基质干细胞(bone marrow stromal cells,BMSCs)联合动静脉血管束植入异种脱蛋白松质骨(xenogeneic deproteinised cancellous bone,XDCB)构筑血管化组织工程骨,为构建组织工程化骨提供新的思路.方法 从兔髂嵴抽骨髓培养制备兔BMSCs,将第3代BMSCs种植于多孔XDCB并进行成骨诱导2周.手术中分离兔隐动、静脉血管束(vascular bundle,VB),以备穿过有孔的XDCB中.取24只新西兰大白兔,其中12只游离双侧兔隐动静脉血管束,共24侧;另外12只兔仅切开股骨外皮肤植入异种骨,共24侧.实验分4组(n=12),A组为单纯材料植入皮下组(XDCB组),B组为干细胞植入材料组(XDCB+ BMSCs组),C组为血管束植入材料组(XDCB+ VB组),D组为干细胞+血管束植入材料组(XDCB+ BMSCs+VB组),各组交叉配对.分别于术后2、4、8周行大体解剖、碱性磷酸酶(ALP)活性检测、茜素红(ARS)染色、组织切片等检查,观察各组移植物血管化情况.结果 D组血管化组织工程骨组可见到血管新生、部分新生骨情况优于B组,也优于C组,而A组的异种骨中未测及相应血管化及成骨效能.结论 BMSCs联合动静脉血管束植入XDCB构筑的血管化组织工程骨有一定的成骨效能,并且可见到材料内部血管化,为构建组织工程化骨提供了新的思路. 相似文献
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Gordon CR Tai CY Suzuki H Strande LF Ramsamooj R Matthews MS Black KS Hewitt CW 《Microsurgery》2007,27(4):348-353
In this review, we examine the applicability of the vascularized bone marrow transplant (VBMT) as an alternative to conventional bone marrow transplantation (BMT). As a new surgical approach, the VBMT is unique by transplantation of the stromal environment that eliminates the need for an engraftment period, provides critical signaling and modulatory functions, and may potentiate tolerance induction. Thus far, VBMT studies have demonstrated an absence of graft-versus-host disease (GVHD) and robust engraftment into nonmanipulated as well as irradiated recipients with evidence of immunological tolerance. Further investigation is needed to determine the applicability of VBMT as an alternative to BMT. 相似文献
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BACKGROUND: Bone marrow (BM) transplantation for treatment of hematological and solid malignancies is routinely carried out in conjunction with radio- and chemotherapy. Many patients achieve complete remission of the malignant process; however, their lymphohematopoietic recovery remains in most cases incomplete. This is probably due to the functional changes in the recipient BM stromal cells subsequent to myeloablative therapy. Transplantation of BM hematopoietic cells in a spatial relationship with stromal cells would give an insight into the kinetics of hematological repopulation of the recipient. The aim of this study was to investigate the lymphopoietic reconstitution of irradiated rats after vascularized bone marrow transplantation (VBMT) in comparison with i.v. bone marrow cell (BMC) infusion. METHODS: Lewis rats were totally irradiated with 8Gy and repopulated with syngeneic BMC introduced i.v. or in orthotopic hind limb graft. Ten days after irradiation and BMC graft BM, peripheral blood (PB) and mesenteric lymph nodes (MLN) were collected. The yield and the phenotype of cells were analyzed. RESULTS: VBMT brings much higher cell repopulation of BM cavities of lethally irradiated rats than BMC infusion. Orthotopic hind limb graft promotes also rapid lymphocyte replenishment of PB and MLN of lethally irradiated syngeneic recipients. The population rate of BMC, PB lymphocytes, and MLN lymphocytes was higher after VBMT than BMC injection in suspension. The percentage of T and B lymphocytes in PB and MLN on day 10 after VBMT was comparable with control values. Reconstituted PB lymphocytes showed two subsets of CD4+ cells: "bright" and "dull." All CD4+ cells in PB lymphocytes of i.v. BMC infused recipients expressed low level of these molecules ("dull" subset). CONCLUSIONS: The results of our studies indicate that the presence of stromal cells in their close relationship with stem cells is essential for the fast lyphohematopoietic repopulation of irradiated recipients. The population of CD4+dull cells may represent immature cells. These cells were not found in MLN of VBMT rats. All MLN CD4+ cells represented the "bright" subset, what suggests that the process of cell maturation may occur in the lymphoid organs. 相似文献
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M. Durlik B. Lukomska P. Religa H. Ziolkowska A. Namysłowski S. Janczewska E. Cybulska J. Soin Z. Gaciong W. L. Olszewski 《Transplant international》1998,11(1):S299-S302
We have noticed that bone marrow transplanted in a vascularized limb graft, providing a continuous supply of donor bone marrow cells (BMC), may prolong the survival time of a skin graft from the same donor. The question arises whether the microchimerism raised plays a role in the prolonged survival of skin allografts. The aim of the study was to follow the development of microchimerism after allogeneic vascularized bone marrow transplantation (VBMTx) concomitantly with the rejection process of transplanted skin. Brown Norway (BN) rats served as donors and Lewis rats as recipients of VBMTx and free skin flap allografts. A hind limb was transplanted, followed by a full-thickness skin graft on the dorsum. Cellular microchimerism was investigated in recipients of VBMTx and skin grafts in blood, spleen, mesenteric lymph node, and bone marrow with the monoclonal antibody OX27 directed against MHC class I polymorphic RT1 on BN cells and quantitatively analyzed in a FACStar. In the VBMTx group, the free skin flap survived 70 days after weaning off cyclosporine A (CsA). An intravenous infusion of BMC in suspension equivalent to that grafted in the hind limb did not prolong skin graft survival after cessation of CsA therapy. Donor-derived cells could be detected in VBMTx recipients as long 70 days after weaning off CsA but not in recipients of i. v. suspension BMC grafting. 相似文献
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Susumu Tamai 《Microsurgery》1995,16(4):179-185
The postoperative hypertropy of the vascularized fibula graft is of particular interest. In order to clarify the etiology of the hypertrophy, we conducted experimental projects on vascularized bone grafts using fluorochrome bone labelings, his-tomorphometry and measurement of blood flow in rats and rabbits. In the murine vascularized tibio-fibula graft for bone defects of the tibia, where mechanical stress to the graft can be expected, cross-sectional bone growth was maintained with acceleration of new bone formation and an alteration of growth direction at 3 weeks after the transplantation. In vascularized bone grafts where no mechanical stress to the graft is expected, more bone resorption was seen than bone formation. In the murine tail bone graft to a bony defect of the femur, the cancellous bone gradually disappeared, and the trabeculae took on an architecture characteristic of the femur. This process slowly transforms the graft into a femur with the morphologic features of a long bone. These results suggested that remodeling of the graft corresponding with the changes in the dynamic environment was accompanied by adequate resorption. The cross-age transplantation of vascularized tibio-fibula grafts in rats showed that the younger the donor, the faster the hypertrophy. Age is one of the important factors affecting remodeling of the vascularized bone graft. The blood flow of the grafted bone in the rabbits increased immediately after the transplantation as a reaction to surgery. Thereafter the blood flow of the graft may depend on the biological demands for new bone formation in adapting to the biomechanical environment of the recipient site. © 1995 Wiley-Liss, Inc. 相似文献