Liver transplantation in Baboons using 1,3-Galactosyltransferase gene-knockout pigs as donors

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As organ shortage is increasing, xenotransplantation may become a potential alternative to increase the number of organs to be transplanted. The swine appears to be the most suitable xenograft donor, because of the similarity of many of its organ systems and physiologic parameters to those of humans. But when a swine organ is transplanted into a primate, hyperacute rejection, induced by a single epitope, galactosyl-alpha-1,3-galactose (Gal), develops rapidly. To avoid this problem, recently genetically-engineered swine, alpha- 1,3-galactosyltransferase knockout (GalT-KO) miniature swine, that do not express the Gal epitope for human natural antibodies were generated. Initial studies undertaken with GalTKO swine kidney, kidney/thymus and heart transplantation have shown promising long-term results. The purpose of this study is to develop a primate model for long-term metabolic and immunosuppressive monitoring of liver xenotransplants obtained from GalT-KO swine. Baboons will undergo pig-to-baboon xenotransplantation. Achieving long-term survival using either standard immunosuppression or a tolerance-inducing protocol, we will monitor physiologic, metabolic and immunologic parameters in the transplant recipient to characterize the function of the xenograft.