嵌合体供者诱导异种皮肤移植免疫耐受的研究

发布时间：2018-02-01 23:17

本文关键词： 造血干细胞嵌合体移植物免疫耐受异种皮肤移植实验研究　出处：《第一军医大学》2006年博士论文　论文类型：学位论文

【摘要】：目前，随着休克复苏、抗感染和代谢支持等治疗措施的不断完善，大面积严重烧伤病人的救治成功率逐渐提高。但自体皮源严重不足依然是导致大面积严重烧伤病人感染、脓毒症和多器官功能衰竭而死亡的主要原因。延长异体(种)皮存活时间、促进微粒自体皮扩增是治疗大面积严重烧伤病人的重要步骤之一。近年来，一些实验证实，利用骨髓干细胞诱导免疫系统尚未发育成熟的异种动物胚胎形成异种造血细胞嵌合体后，将其组织器官移植给造血干细胞的供者，可诱导产生“移植物免疫耐受”和“免疫适应性”。但有关异种造血细胞嵌合体作为异种皮肤移植的供者，能否产生免疫适应性从而延长其存活时间的动物实验和临床研究尚未见报道；对异种造血细胞嵌合体供者诱导的异种移植免疫耐受的机制尚不清楚。补体调节蛋白的种属差异是导致异种移植超急性排斥反应的主要原因。作者推测，嵌合体供者诱导的异种移植物免疫耐受，可能与嵌合体内的异种嵌合细胞表达其种属特异性的补体调节蛋白有关。本研究拟通过检测嵌合体组织中嵌合的异源性细胞及其补体调节蛋白(hCD55和hCD59)的分布，分析探讨造血细胞嵌合体供者诱导异种皮肤移植免疫耐受的可能性及其机制，为嵌合体供者诱导异种皮肤移植耐受的实验研究提供理论依据；通过嵌合体供者异种皮肤移植的实验研究，观察嵌合体供者异种皮肤移植后，移植物排斥时间和创面愈合时间，为嵌合体供者诱导异种皮肤移植免疫耐受的临床研究奠定基础。
[Abstract]:At present, with the development of shock resuscitation, anti-infection and metabolic support, and other treatment measures continue to improve. The success rate of large area severe burn patients is increasing gradually, but the serious shortage of autogenous skin source is still leading to the infection of large area severe burn patients. The main causes of death due to sepsis and multiple organ failure. Prolonging the survival time of allogeneic skin and promoting the amplification of autogenous skin is one of the important steps in the treatment of patients with severe burns in large area. Some experiments have confirmed that bone marrow stem cells are used to induce immature xenogeneic animal embryos to form heterogeneous hematopoietic cell chimerism and then transplant their tissues and organs to donors of hematopoietic stem cells. "Graft tolerance" and "immune adaptability" can be induced, but the xenohematopoietic cell chimera can be used as a donor for xenogeneic skin transplantation. Animal experiments and clinical studies on the ability of immune adaptation to prolong its survival time have not been reported. The mechanism of xenotransplantation tolerance induced by xenohematopoietic chimeric donors is unclear. The difference of complement regulatory protein species is the main cause of hyperacute rejection in xenotransplantation. The authors speculate that chimeric donor induced xenograft tolerance. This study was intended to detect the chimeric heterogenous cells and their complement regulatory proteins (CMIs) in chimeric tissues. The distribution of hCD55 and hCD59). To explore the possibility and mechanism of immune tolerance induced by hematopoietic cell chimeric donors in xenograft skin transplantation, and to provide theoretical basis for the experimental study of xenograft tolerance induced by chimeric donors. The allograft rejection time and wound healing time after chimeric donor xenotransplantation were observed. To lay a foundation for the clinical study of immune tolerance induced by chimeric donors in xenotransplantation.
【学位授予单位】：第一军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392.4

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