Strategic approach with the aid of molecular biology in regulation of xenograft rejection

借助分子生物学调节异种移植排斥的策略方法

基本信息

批准号：
11470243
负责人：
YOKOYAMA Itsuo
金额：
$ 9.28万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Approximately seven hundred millions of people die each year in Japan, in which end-stage failure of vital organs such as heart, liver and kidney. Definitive treatment for such diseases is yet established and an ultimate way of saving patients with such diseases is implantation of artificial organs that fulfill the complicated function of the organ. Organ transplantation is a currently available definitive treatment for those end-stage diseases, though not an ultimate form of remedy. Allotransplantation between the human is now widely performed, although a limited number of organ sauce and an unnecessary burden on the recipients are the two obstacles for its development. Xenotransplantation can be an alternate method of organ transplantation such as pig to human transplantation since the donor organ can be supplied unlimitedly. However, a vigorous rejection occurs in the xenotransplantation in the pig to human, so called discordant transplantation. The aim of the present study was to investigate how we could overcome the hyperacute rejection.The mechanism of hyeracute rejection has been partially understood and the key event is an interaction between the 1-3 alpha galactose of the pig organ and the natural antibody of the human serum. The findings that we obtained are the followings : 1) the effect of cell death inducing factors and the viability of the xeno-graft ; 2) Apoptosis of the xeno-graft (endothelial cells) cells and its induction mechanism, or interaction of the cell-surface receptors, super-oxide and caspases ; 3) clonins of the 1-3 alpha galactosyl transferase and its degrading enzyme of galactosidase.We believe that he results of the present study can contribute more effective regulation of the hyperacute rejection in the discordant xenotransplantation that can be applicable to future clinical use.

日本每年约有七亿人死于心脏、肝脏和肾脏等重要器官的终末期衰竭。此类疾病的确切治疗方法尚未建立，拯救此类疾病患者的最终方法是植入能够实现器官复杂功能的人造器官。器官移植是目前针对这些终末期疾病的有效治疗方法，但不是最终的治疗形式。人与人之间的同种异体移植现已广泛开展，但器官酱数量有限和对受者造成不必要的负担是其发展的两个障碍。异种移植可以是器官移植的替代方法，例如猪到人的移植，因为供体器官可以无限供应。然而，猪向人的异种移植会出现强烈的排斥反应，即所谓的不协调移植。本研究的目的是研究如何克服超急性排斥反应。超急性排斥反应的机制已部分了解，关键事件是猪器官的 1-3 α 半乳糖与猪器官的天然抗体之间的相互作用。人血清。我们获得的结果如下：1）细胞死亡诱导因子的影响和异种移植物的活力； 2）异种移植（内皮细胞）细胞的凋亡及其诱导机制，或细胞表面受体、超氧化物和半胱天冬酶的相互作用； 3）1-3α半乳糖基转移酶及其降解酶半乳糖苷酶的克隆素。我们相信本研究结果可以为不一致的异种移植中的超急性排斥反应提供更有效的调节，可应用于未来的临床使用。