嵌合體供者誘導(dǎo)異種皮膚移植免疫耐受的研究
本文關(guān)鍵詞: 造血干細(xì)胞 嵌合體 移植物免疫耐受 異種皮膚移植 實(shí)驗(yàn)研究 出處:《第一軍醫(yī)大學(xué)》2006年博士論文 論文類型:學(xué)位論文
【摘要】:目前,隨著休克復(fù)蘇、抗感染和代謝支持等治療措施的不斷完善,大面積嚴(yán)重?zé)齻∪说木戎纬晒β手饾u提高。但自體皮源嚴(yán)重不足依然是導(dǎo)致大面積嚴(yán)重?zé)齻∪烁腥、膿毒癥和多器官功能衰竭而死亡的主要原因。延長(zhǎng)異體(種)皮存活時(shí)間、促進(jìn)微粒自體皮擴(kuò)增是治療大面積嚴(yán)重?zé)齻∪说闹匾襟E之一。近年來(lái),一些實(shí)驗(yàn)證實(shí),利用骨髓干細(xì)胞誘導(dǎo)免疫系統(tǒng)尚未發(fā)育成熟的異種動(dòng)物胚胎形成異種造血細(xì)胞嵌合體后,將其組織器官移植給造血干細(xì)胞的供者,可誘導(dǎo)產(chǎn)生“移植物免疫耐受”和“免疫適應(yīng)性”。但有關(guān)異種造血細(xì)胞嵌合體作為異種皮膚移植的供者,能否產(chǎn)生免疫適應(yīng)性從而延長(zhǎng)其存活時(shí)間的動(dòng)物實(shí)驗(yàn)和臨床研究尚未見報(bào)道;對(duì)異種造血細(xì)胞嵌合體供者誘導(dǎo)的異種移植免疫耐受的機(jī)制尚不清楚。 補(bǔ)體調(diào)節(jié)蛋白的種屬差異是導(dǎo)致異種移植超急性排斥反應(yīng)的主要原因。作者推測(cè),嵌合體供者誘導(dǎo)的異種移植物免疫耐受,可能與嵌合體內(nèi)的異種嵌合細(xì)胞表達(dá)其種屬特異性的補(bǔ)體調(diào)節(jié)蛋白有關(guān)。本研究擬通過(guò)檢測(cè)嵌合體組織中嵌合的異源性細(xì)胞及其補(bǔ)體調(diào)節(jié)蛋白(hCD55和hCD59)的分布,分析探討造血細(xì)胞嵌合體供者誘導(dǎo)異種皮膚移植免疫耐受的可能性及其機(jī)制,為嵌合體供者誘導(dǎo)異種皮膚移植耐受的實(shí)驗(yàn)研究提供理論依據(jù);通過(guò)嵌合體供者異種皮膚移植的實(shí)驗(yàn)研究,觀察嵌合體供者異種皮膚移植后,移植物排斥時(shí)間和創(chuàng)面愈合時(shí)間,為嵌合體供者誘導(dǎo)異種皮膚移植免疫耐受的臨床研究奠定基礎(chǔ)。
[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.
【學(xué)位授予單位】:第一軍醫(yī)大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2006
【分類號(hào)】:R392.4
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