A review of pig liver xenotransplantation: Current problems and recent progress

作者：Xuan Zhang, Xiao Li, Zhao-Xu Yang, Kaishan Tao, Quancheng Wang, Bin Dai, Shibin Qu, Wei Peng, Hong Zhang, David K. C. Cooper, Kefeng Dou · 发表于：Xenotransplantation · 年份：2019 · DOI：10.1111/xen.12497 · 被引用次数：48 · 研究领域：Xenotransplantation and immune response、Organ Transplantation Techniques and Outcomes、Liver physiology and pathology

Pig liver xenotransplantation appears to be more perplexing when compared to heart or kidney xenotransplantation, even though great progress has been achieved. The relevant molecular mechanisms involved in xenogeneic rejection, including coagulopathy, and particularly thrombocytopenia, are complex, and need to be systematically investigated. The deletion of expression of Gal antigens in the liver graft highlights the injurious impact of nonGal antigens, which continue to induce humoral rejection. Innate immunity, particularly mediated by macrophages and natural killer cells, interplays with inflammation and coagulation disorders. Kupffer cells and liver sinusoidal endothelial cells (LSECs) together mediate leukocyte, erythrocyte, and platelet sequestration and phagocytosis, which can be exacerbated by increased cytokine production, cell desialylation, and interspecies incompatibilities. The coagulation cascade is activated by release of tissue factor which can be dependent or independent of the xenoreactive immune response. Depletion of endothelial anticoagulants and anti-platelet capacity amplify coagulation activation, and interspecies incompatibilities of coagulation-regulatory proteins facilitate dysregulation. LSECs involved in platelet phagocytosis and transcytosis, coupled with hepatocyte-mediated degradation, are responsible for thrombocytopenia. Adaptive immunity could also be problematic in long-term liver graft survival. Currently, relevant evidence and study resul...