异种移植
移植
生物
转基因生物
内源性逆转录病毒
免疫系统
器官移植
CD154
遗传增强
免疫学
基因
抗体
医学
遗传学
CD40
细胞毒性T细胞
内科学
基因组
体外
作者
Syed Sikandar Raza,Hidetaka Hara,W.H. Eyestone,David Ayares,David C. Cleveland,David K.C. Cooper
出处
期刊:Comparative Medicine
[American Association for Laboratory Animal Science]
日期:2024-04-01
卷期号:74 (2): 33-48
标识
DOI:10.30802/aalas-cm-23-000030
摘要
The pig has long been used as a research animal and has now gained importance as a potential source of organs for clinical xenotransplantation. When an organ from a wild-type (i. e., genetically unmodified) pig is transplanted into an immunosuppressed nonhuman primate, a vigorous host immune response causes hyperacute rejection (within minutes or hours). This response has been largely overcome by 1) extensive gene editing of the organ-source pig and 2) the administration to the recipient of novel immunosuppressive therapy based on blockade of the CD40/CD154 T cell costimulation pathway. Gene editing has consisted of 1) deletion of expression of the 3 known carbohydrate xenoantigens against which humans have natural (preformed) antibodies and 2) the introduction of human 'protective' genes. The combination of gene editing and novel immunosuppressive therapy has extended life-supporting pig kidney graft survival to greater than 1 y and of pig heart survival to up to 9 mo. This review briefly describes the techniques of gene editing, the potential risks of transfer of porcine endogenous retroviruses with the organ, and the need for breeding and housing of donor pigs under biosecure conditions.
科研通智能强力驱动
Strongly Powered by AbleSci AI