What Are the Immune Obstacles to Liver Xenotransplantation Which Is Promising for Patients with Hepatocellular Carcinoma
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REVIEW ARTICLE
What Are the Immune Obstacles to Liver Xenotransplantation Which Is Promising for Patients with Hepatocellular Carcinoma? Sezai Yilmaz 1,2
&
Tolga Sahin 1
&
Kutay Saglam 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose 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 ⍺1-3 galactose, N- glycolylneuraminic acid, β1,4-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. Keywords Liver transplantation . Xenotransplantation . Genetic engineering . Transgenic pigs . Hepatocellular carcinoma
Abbreviations AFP AMR ATG β4GalNT2 Gal ⍺1-3 Gal GPC-3
Alpha fetoprotein Antibody-mediated rejection Thymoglobulin Acetylgalactosaminyl transferase Galactose ⍺1-3 galactose Glypican-3
* Sezai Yilmaz [email protected] 1
Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280 Malatya, Turkey
2
Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Elazig Yolu 10. Km, 44280 Malatya, Turkey
HCC HIV hTERT LTx KO MAGE-A MDSC NY-ESO-1 (CTAG1B) Neu5Gc SSX-2
Hepatocellular carcinoma Human immunodeficiency virus Human telomerase reverse transcriptase Liver transplantation Knockout Melanoma antigen gene A Myeloid-derived suppressor cells Cancer testis a
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