title: Current status of hepatocyte xenotransplantation.
abstract: The treatment of acute liver failure, a condition with high mortality, comprises optimal clinical care, and in severe cases liver transplantation. However, there are limitations in availability of organ donors. Hepatocyte transplantation is a promising alternative that could fill the medical need, in particular as the bridge to liver transplantation. Encapsulated porcine hepatocytes represent an unlimited source that could function as a bioreactor requiring minimal immunosuppression. Besides patients with acute liver failure, patients with alcoholic hepatitis who are unresponsive to a short course of corticosteroids are a target for hepatocyte transplantation. In this review we present an overview of the innate immune barriers in hepatocyte xenotransplantation, including the role of complement and natural antibodies; the role of phagocytic cells and ligands like CD47 in the regulation of phagocytic cells; and the role of Natural Killer cells. We present also some illustrations of physiological species incompatibilities in hepatocyte xenotransplantation, such as incompatibilities in the coagulation system. An overview of the methodology for cell microencapsulation is presented, followed by proof-of-concept studies in rodent and nonhuman primate models of fulminant liver failure: these studies document the efficacy of microencapsulated porcine hepatocytes which warrants progress towards clinical application. Lastly, we present an outline of a provisional clinical trial, that upon completion of preclinical work could start within the upcoming 2-3 years.
authors.affiliation: Visceral and Transplantation Surgery, Department of Surgery, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland. Electronic address: Raphael.meier@hcuge.ch.
authors.forename: Raphael P H
authors.initials: RPH
authors.lastname: Meier
authors.affiliation: Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Nalu
authors.initials: N
authors.lastname: Navarro-Alvarez
authors.affiliation: Visceral and Transplantation Surgery, Department of Surgery, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.affiliation: Visceral and Transplantation Surgery, Department of Surgery, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Schuurman
authors.affiliation: Cell Transplantation and Regenerative Medicine, Department of Laboratory Medicine, Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Stephen
authors.initials: S
authors.lastname: Strom
authors.affiliation: Visceral and Transplantation Surgery, Department of Surgery, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Leo H
authors.initials: LH
authors.lastname: Bühler
mesh_terms: D000818:Animals; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D007113:Immunity, Innate; D007165:Immunosuppression Therapy / Q000379:methods; D017114:Liver Failure, Acute / Q000628:therapy; D016031:Liver Transplantation / Q000379:methods*; D013552:Swine; D014183:Transplantation, Heterologous / Q000379:methods
keywords: Acute liver failure; Alcoholic hepatitis; Animal models of liver failure; Cell transplantation; Innate immunity; Physiologic species incompatibilities; Porcine hepatocytes; Xenotransplantation