抗凋亡基因BCL2在灵长类异种器官形成中的作用研究

器官移植是治疗器官衰竭病人最有效的手段，但器官短缺问题严重。如何获得功能正常并可用于移植的人的器官目前是科学界的研究难点和热点。通过注射干细胞的囊胚补偿被认为是最有希望在体内获得异种器官的方法。在啮齿类动物的研究中，利用囊胚嵌合可以在异种体内获得完整的器官。本研究团队前期的研究发现，增加人多能性干细胞的抗凋亡能力，可以提高其在啮齿类的异种嵌合能力。结合抗凋亡作用和器官缺陷模型，是否可以在大动物中获得完整的人类器官尚不可知。为了避免伦理问题，本项目拟利用食蟹猴干细胞，通过过表达抗凋亡基因BCL2（mkES-BCL2），研究其在FAH基因缺陷猪中的嵌合能力，并尝试获得具有正常生理功能的灵长类来源的肝脏细胞和肝脏器官，为人类器官再生探索一条可行的路径。

Organ transplantation is the most effective method for treating patients with organ failure, but organ shortage is a serious problem. How to obtain human organs that are functional and can be used for transplantation is currently a difficult and hot research topic in the scientific community. Blastocyst complementation by pluripotent stem cell (PSC) injection is believed to be the most promising method to generate organs. In rodent research, blastocyst chimerism can be used to obtain complete organs in the xenograft. Earlier studies by our research team found that increasing the anti-apoptotic capacity of human pluripotent stem cells can enhance the chimeric ability in rodents. It is unknown whether complete human organs can be obtained combining anti-apoptotic effects and organ defect models in large animals. In order to avoid ethical issues, this project intends to use cynomolgus monkey stem cells to overexpress the anti-apoptotic gene BCL2 (mkES-BCL2), and study its chimeric ability in FAH-deficient pigs to obtain liver cells and organs with normal physiological functions, and explore a feasible path for human organ regeneration.