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

随着器官短缺的加剧，异种移植可能成为增加移植器官数量的潜在替代方案。猪似乎是最合适的异种移植供体，因为它的许多器官系统和生理参数与人类相似。但是，当猪器官移植到灵长类动物，超急性排斥反应，由一个单一的表位，半乳糖基-α-1，3-半乳糖（Gal），诱导，迅速发展。为了避免这个问题，最近产生了不表达人天然抗体的Gal表位的基因工程猪，α-1，3-半乳糖基转移酶敲除（GalT-KO）小型猪。用GalTKO猪肾、肾/胸腺和心脏移植进行的初步研究显示了有希望的长期结果。本研究的目的是开发一种灵长类动物模型，用于长期监测从GalT-KO猪获得的肝脏异种移植物的代谢和免疫抑制。狒狒将接受猪到狒狒的异种移植。使用标准免疫抑制或耐受诱导方案实现长期存活，我们将监测移植受体的生理学、代谢和免疫学参数，以表征异种移植物的功能。

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.