Establishment of Transgenic Pig for Organ Xenotransplantation

点击翻译按钮获取中文摘要

In organ xenotransplantetion, hyperacute rejection, induced by natural antibody, xenoantigen, and complement, occurs in a few minutes or hours after reperfusion. In this study, based on the in vitro study, in which the double transduction of complement regulatory factors (DAF and HRF20) is more effective than the single transduction on the xenogeneic cells to inhibit complement-dependent cytotoxicity, double transgenic mice with DAF and HRF20 genes were established. Then the construction of transgenic pig with DAF,HRF20, and membrane cofactor protein (MCP) was studied. To control the expression of major xenoantigen GalalphaGal, double knockout of alpha (1,3) GT gene on embryonic stem (ES) cells was examined. As another strategy to control GalalphaGal, it was demonstrated that the transduction of alpha (1,2) FT gene to the xenogenic cell inhibited the GaalphaaGal expression and complement-dependent cytotoxicity, and the transgenic pig with alpha (1,2) FT gene was established. Thus it is concluded that the construction of transgenic pigs with complement regulatory factor genes and alpha (1,2) FT gene is useful for the successful clinical xenotransplantation.