Vascularized Thymosternal Composite Tissue Allo- and Xenotransplantation in Nonhuman Primates: Initial Experience.
Vascularized Thymosternal Composite Tissue Allo- and Xenotransplantation in Nonhuman Primates: Initial Experience.
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非人灵长类动物的血管化胸骨复合组织同种异体移植：初步经验。
DOI：
10.1097/gox.0000000000001538
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Nam,ArthurJ
中科院分区：
文献类型：
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作者：
Sendil,Selin;Diaconu,SilviuC;O'Neill,NatalieA;Burdorf,Lars;Tatarov,Ivan;Parsell,DawnM;Azimzadeh,AgnesM;Pierson3rd,RichardN;Nam,ArthurJ
背景：血管化复合同种异体移植受限于标准免疫抑制策略相关的并发症。在复合器官和软组织血管化复合同种异体移植模型中，血管化胸腺和骨髓已被证明可促进移植物存活时间延长。我们报告开发的非人灵长类动物血管化胸腺胸骨复合组织移植模型作为一个平台，以解决捐助者特异性免疫耐受诱导strategies.Methods：血管化胸腺胸骨同种异体移植物（皮肤，肌肉，胸腺，胸骨）之间的MHC-不匹配的恒河猴（可行性研究）和狒狒（长期生存研究），与端到端的供体主动脉和SVC的受体股动脉血管。将男性同种异体移植物移植到女性的下腹壁，并给予临床适用的免疫抑制剂。定期完成皮肤活检和免疫学检测，并使用聚合酶链反应对狒狒Y染色体特异性定量嵌合体。结果：四个异基因和2异种移植，表现出一致的技术可行性。在1例接受抗CD 40免疫抑制治疗的狒狒胸腺胸骨同种异体移植受者中，观察到第5天后外周血微嵌合体丢失，并预期在第13天发生移植物排斥反应。在第二个同种异体移植物中，当皮肤红斑和瘀斑伴同种异体移植物肿胀时，从第6天开始用抗胸腺细胞球蛋白治疗，微嵌合体持续存在，直到第一个月后免疫抑制减少，同种异体移植物存活至87天，即停止免疫抑制治疗后1个月。我们建立了同种异体和异种复合血管化胸腺胸骨移植临床前模型，这将有助于研究主要血管化供体骨髓和胸腺的作用。
Background:Vascularized composite allotransplantation is constrained by complications associated with standard immunosuppressive strategies. Vascularized thymus and bone marrow have been shown to promote prolonged graft survival in composite organ and soft-tissue vascularized composite allotransplantation models. We report development of a nonhuman primate vascularized thymosternal composite tissue transplant model as a platform to address donor-specific immune tolerance induction strategies.Methods:Vascularized thymosternal allograft (skin, muscle, thymus, sternal bone) was transplanted between MHC-mismatched rhesus monkeys (feasibility studies) and baboons (long-term survival studies), with end-to-side anastomoses of the donor aorta and SVC to the recipient common femoral vessels. A male allograft was transplanted to a female’s lower abdominal wall, and clinically applicable immunosuppression was given. Skin biopsies and immunological assays were completed at regular intervals, and chimerism was quantified using polymerase chain reaction specific for baboon Y chromosome.Results:Four allo-and 2 xenotransplants were performed, demonstrating consistent technical feasibility. In 1 baboon thymosternal allograft recipient treated with anti-CD40–based immunosuppression, loss of peripheral blood microchimerism after day 5 was observed and anticipated graft rejection at 13 days. In the second allograft, when cutaneous erythema and ecchymosis with allograft swelling was treated with anti-thymocyte globulin starting on day 6, microchimerism persisted until immunosuppression was reduced after the first month, and the allograft survived to 87 days, 1 month after cessation of immunosuppression treatment.Conclusions:We established both allo-and xeno-composite vascularized thymosternal transplant preclinical models, which will be useful to investigate the role of primarily vascularized donor bone marrow and thymus.