Yilmaz, SezaiSahin, TolgaSaglam, Kutay2024-08-042024-08-0420201941-66281941-6636https://doi.org/10.1007/s12029-020-00495-9https://hdl.handle.net/11616/99474Purpose Liver transplantation is the most important achievement in the twentieth and twenty-first century. It is the gold standard treatment for hepatocellular carcinoma. However, it provides the best results when performed under strict selection criteria. Nevertheless, organ supply is overwhelmed by the number of patients on the waiting list. There are certain strategies to expand the donor pool such as split liver transplantation, use of extended criteria donors, and living donor liver transplantation. Xenotransplantation can also be a strategy in decreasing the organ shortage. We reviewed the current status of xenotransplantation. Methods We evaluated the historical attempts of xenotransplantation to humans and also made a summary of the preclinical studies in the field. Results Molecular biology and genetic engineering are developing with an incredible speed. There are great achievements made in cell therapy, 3D bioprinting of the organs, and ultimately xenotransplantation. There is a vast amount of problems to be handled before evaluating the efficacy of xenotransplantation in the treatment of hepatocellular carcinoma. Major problems include antibody-mediated rejection to antigens such as galactose alpha 1-3 galactose, N- glycolylneuraminic acid, beta 1,4-Nacetylgalactosaminyltransferase, lethal thrombocytopenia, and erythrocyte sequestration. Antibody mediated rejection to these specific antigens are addressed using gene editing technology including CRISPR Cas9, TALEN and other recombination methods. Although hyperacute rejection is reduced, long-term survival could not be achieved in experimental models. Conclusion The future is yet to come, there are developments made in the field of genetic editing, immunosuppressive medication, and pretransplant desensitization techniques. Therefore, we believe that xenotransplantation will be in clinical practice, at least for treatment of critically ill patients.eninfo:eu-repo/semantics/closedAccessLiver transplantationXenotransplantationGenetic engineeringTransgenic pigsHepatocellular carcinomaReview Article514120912143283322210.1007/s12029-020-00495-92-s2.0-85089732066Q3WOS:000562325600001N/A