Incidence of hyperacute rejection in pig-to-primate transplantation using organs from hDAF-transgenic donors

作者：Henk‐Jan Schuurman, Gilda Pino‐Chavez, M. J. Phillips, Lucy J. Thomas, David J. White, Emanuele Cozzi · 发表于：Transplantation · 年份：2002 · DOI：10.1097/00007890-200204150-00024 · 被引用次数：114 · 研究领域：Xenotransplantation and immune response、Virus-based gene therapy research、Animal Genetics and Reproduction

BACKGROUND: Cynomolgus monkeys or baboons received under immunosuppression kidney or heart grafts from pigs transgenic for human decay-accelerating factor (hDAF) or from control pigs. Hyperacute rejection (HAR) is often difficult to differentiate from nonimmunological causes of organ or recipient dysfunction (NIC), and therefore, a thorough pathology review of all cases with 0-4 days survival (inclusive) was conducted. METHODS: Pathology slides were blinded and together with limited clinical data reviewed by two pathologists. After unblinding, data were compared with the original diagnosis made during the course of the program, and a final diagnosis was reached considering the complete clinical dataset. RESULTS: Life-supporting kidney transplantation was performed in 245 cynomolgus monkeys (234 hDAF, 11 controls), of which 102 cases had 0-4 day survival. None of the hDAF cases showed HAR, whereas this occurred in 27% of controls (P<10-6). Heterotopic heart transplantation was performed in 65 monkeys (57 hDAF, 8 controls), of which 41 cases had 0-4 day survival. HAR was observed in 7% of hDAF cases and in 57% of controls (P=0.002). Heterotopic heart transplantation in baboons was performed in 33 animals (28 hDAF, 5 controls), of which 15 cases had 0-4 day survival. HAR was observed in 11% of hDAF cases and in 20% of controls. Sixteen baboons were subjected to orthotopic heart transplantation, all from hDAF donors, out of which eight survived 0-4 days. The incidence of HAR was ...