Hepatic Medicine: Evidence and Research (Feb 2024)
Chimeric Livers: Interspecies Blastocyst Complementation and Xenotransplantation for End-Stage Liver Disease
Abstract
Madelyn J Blake,1 Clifford J Steer2 1Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA; 2Departments of Medicine, and Genetics, Cell Biology and Development, University of Minnesota Medical School, Minneapolis, MN, USACorrespondence: Madelyn J Blake, Department of Medicine, University of Minnesota Medical School, 420 Delaware Street SE, MMC 195, Minneapolis, MN, 55455, USA, Email [email protected] Clifford J Steer, Department of Medicine, University of Minnesota Medical School, 420 Delaware Street SE, MMC 36, Minneapolis, MN, 55455, USA, Email [email protected]: Orthotopic liver transplantation (OLT) currently serves as the sole definitive treatment for thousands of patients suffering from end-stage liver disease; and the existing supply of donor livers for OLT is drastically outpaced by the increasing demand. To alleviate this significant gap in treatment, several experimental approaches have been devised with the aim of either offering interim support to patients waiting on the transplant list or bioengineering complete livers for OLT by infusing them with fresh hepatic cells. Recently, interspecies blastocyst complementation has emerged as a promising method for generating complete organs in utero over a short timeframe. When coupled with gene editing technology, it has brought about a potentially revolutionary transformation in regenerative medicine. Blastocyst complementation harbors notable potential for generating complete human livers in large animals, which could be used for xenotransplantation in humans, addressing the scarcity of livers for OLT. Nevertheless, substantial experimental and ethical challenges still need to be overcome to produce human livers in larger domestic animals like pigs. This review compiles the current understanding of interspecies blastocyst complementation and outlines future possibilities for liver xenotransplantation in humans.Keywords: end-stage liver disease, interspecies blastocyst complementation, blastocyst complementation, chimeras, xenotransplantation
