Genetic engineering of pigs for xenotransplantation to overcome immune rejection and physiological incompatibilities: The first clinical steps
作者全名："Lei, Tiantian; Chen, Lin; Wang, Kejing; Du, Suya; Gonelle-Gispert, Carmen; Wang, Yi; Buhler, Leo H."
作者地址："[Lei, Tiantian; Chen, Lin; Wang, Kejing] Chongqing Med Univ, Women & Childrens Hosp, Chongqing Hlth Ctr Women & Children, Dept Pharm, Chongqing, Peoples R China; [Du, Suya] Univ Elect Sci & Technol China, Sichuan Canc Hosp & Inst, Sichuan Canc Ctr, Sch Med,Dept Clin Pharm, Chengdu, Sichuan, Peoples R China; [Gonelle-Gispert, Carmen; Buhler, Leo H.] Univ Fribourg, Fac Sci & Med, Fribourg, Switzerland; [Wang, Yi] Univ Elect Sci & Technol China, Sichuan Acad Med Sci, Dept Crit Care Med, Chengdu, Peoples R China; [Wang, Yi] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Chengdu, Peoples R China"
通信作者："Gonelle-Gispert, C; Buhler, LH (通讯作者)，Univ Fribourg, Fac Sci & Med, Fribourg, Switzerland.; Wang, Y (通讯作者)，Univ Elect Sci & Technol China, Sichuan Acad Med Sci, Dept Crit Care Med, Chengdu, Peoples R China.; Wang, Y (通讯作者)，Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Chengdu, Peoples R China."
来源：FRONTIERS IN IMMUNOLOGY
关键词：genetically modified pigs; immunological rejection; innate and adaptive immune responses; coagulation dysfunction; systemic inflammation; pig-to-nonhuman primate xenotransplantation; clinical trials of xenotransplantation
摘要："Xenotransplantation has the potential to solve the shortfall of human organ donors. Genetically modified pigs have been considered as potential animal donors for human xenotransplantation and have been widely used in preclinical research. The genetic modifications aim to prevent the major species-specific barriers, which include humoral and cellular immune responses, and physiological incompatibilities such as complement and coagulation dysfunctions. Genetically modified pigs can be created by deleting several pig genes related to the synthesis of various pig specific antigens or by inserting human complement- and coagulation-regulatory transgenes. Finally, in order to reduce the risk of infection, genes related to porcine endogenous retroviruses can be knocked down. In this review, we focus on genetically modified pigs and comprehensively summarize the immunological mechanism of xenograft rejection and recent progress in preclinical and clinical studies. Overall, both genetically engineered pig-based xenografts and technological breakthroughs in the biomedical field provide a promising foundation for pig-to-human xenotransplantation in the future."
基金机构："National Science Foundation of China [81802504, 81872207]; Sichuan Science and Technology Bureau [2022YTH0005, 2021YJ0564, 2019YFS0439]; Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0855]; Sichuan Medical Association [Q19037]; Chengdu Science and Technology Bureau [2021-YF05-00225-SN]; Insuleman foundation; Child foundation; foundation la Colombe"
基金资助正文："This study was sponsored by the National Science Foundation of China (81802504, 81872207), the Sichuan Science and Technology Bureau (2022YTH0005, 2021YJ0564 and 2019YFS0439), the Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0855), Sichuan Medical Association (Q19037), and Chengdu Science and Technology Bureau (2021-YF05-00225-SN). LB and CG-G are supported by the Insuleman foundation, Child foundation and the foundation la Colombe"