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

点击翻译按钮获取中文摘要

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.