Gene-Modified Pigs as Donors for Liver Xenotransplantation: How Many Modifications Are Needed?

Liver transplantation is currently the only viable treatment option for patients suffering from end-stage liver disease or acute liver failure. However, the scarcity of organ donors poses a major challenge for liver transplants. Pigs are a promising candidate for future organ xenotransplantation, potentially serving as a clinical bridge to allotransplantation. However, utilization of pigs as donors to human faced complications such as hyperacute rejection (HAR), thrombocytopenia, blood coagulation dysfunction, and physiological function disorders. Recent advances in genetically modified pig development bring clinical xenotransplantation closer to reality. In this review, we present an overview of the history of pig liver xenotransplantation, summarize the latest progress in pig-to-nonhuman primate liver transplantation models, and focus on optimizing genetic modification combinations of donor pigs to solve inflammation problems, ameliorate blood system dysfunction, break biological incompatibility between pigs and nonhuman primates/humans and prolong the survival time of liver xenografts.