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

在日本，每年大约有7亿人死于心脏、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确立，拯救此类疾病患者的最终方法是植入人造器官，以实现器官的复杂功能。器官移植是目前可用于这些终末期疾病的最终治疗方法，尽管不是最终的治疗形式。人与人之间的同种异体移植现在被广泛进行，尽管数量有限的器官酱和受者不必要的负担是其发展的两个障碍。异种器官移植可以作为器官移植的一种替代方法，例如猪到人的移植，因为供体器官可以无限供应。然而，在猪到人的异种移植中，出现了强烈的排斥反应，即非协调性移植。本研究的目的是探讨如何克服超急性排斥反应。超急性排斥反应的机制已被部分了解，关键事件是猪器官的1-3α半乳糖与人血清天然抗体之间的相互作用。1)细胞死亡诱导因素对异种移植物存活的影响；2)异种移植物(内皮细胞)细胞的凋亡及其诱导机制，或细胞表面受体、超氧化物和半胱氨酸天冬氨酸酶的相互作用；3)半乳糖基转移酶及其降解酶1-3的克隆。我们相信，本研究结果将有助于更有效地调节异种异种移植的超急性排斥反应，可应用于临床。

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.