Cytokine profiles in Tibetan macaques following α‐1,3‐galactosyltransferase‐knockout pig liver xenotransplantation

作者：Zhuochao Zhang, Xiao Li, Hong Zhang, Xuan Zhang, Hui Chen, Dengke Pan, Hongchen Ji, Liang Zhou, Juan Ling, Jingshi Zhou, Shuqiang Yue, Desheng Wang, Zhao-Xu Yang, Kaishan Tao, Kefeng Dou · 发表于：Xenotransplantation · 年份：2017 · DOI：10.1111/xen.12321 · 被引用次数：35 · 研究领域：Xenotransplantation and immune response、Organ Transplantation Techniques and Outcomes、T-cell and B-cell Immunology

BACKGROUND: Pig-to-nonhuman primate orthotopic liver xenotransplantation is often accompanied by thrombocytopenia and coagulation disorders. Furthermore, the release of cytokines can trigger cascade reactions of coagulation and immune attacks within transplant recipients. To better elucidate the process of inflammation in liver xenograft recipients, we utilized a modified heterotopic auxiliary liver xenotransplantation model for xeno-immunological research. We studied the cytokine profiles and the relationship between cytokine levels and xenograft function after liver xenotransplantation. METHODS: Appropriate donor and recipient matches were screened using complement-dependent cytotoxicity assays. Donor liver grafts from α1,3-galactosyltransferase gene-knockout (GTKO) pigs or GTKO pigs additionally transgenic for human CD47 (GTKO/CD47) were transplanted into Tibetan macaques via two different heterotrophic auxiliary liver xenotransplantation procedures. The cytokine profiles, hepatic function, and coagulation parameters were monitored during the clinical course of xenotransplantation. RESULTS: Xenograft blood flow was stable in recipients after heterotopic auxiliary transplantation. A Doppler examination indicated that the blood flow speed was faster in the hepatic artery (HA) and hepatic vein (HV) of xenografts subjected to the modified Sur II (HA-abdominal aorta+HV-inferior vena cava) procedure than in those subjected to our previously reported Sur I (HA-splenic artery+HV-l...