title: Clinical pig liver xenotransplantation: how far do we have to go?
abstract: As pigs are currently the preferred species for organ xenotransplantation, initial experience in liver xenotransplantation with wild-type (WT) pigs, advances in the development of genetically modified pigs, and recent studies using livers from them are reviewed. The xenotransplantation of livers from pigs transgenic for the human complement regulatory protein (CRP) CD55 or from α1,3-galactosyltransferase gene-knockout pigs+/- additionally transgenic for the CRP CD46 (GTKO/CD46 pigs) is associated with the survival of approximately 1 week. Satisfactory hepatic function has been documented, lending support to the concept that the pig liver might provide a bridge to allotransplantation. However, although significant features of rejection have not been documented, the development of an immediate thrombocytopenia after graft reperfusion is problematic and leads to spontaneous hemorrhage within the body cavities, native organs, and graft. Current studies are being directed to understand the factors causing the activation, aggregation, or phagocytosis of platelets, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes, and Kupffer cells. If this problem can be resolved, a clinical trial of pig liver xenotransplantation as a bridge to allotransplantation may be both feasible and justified.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
authors.forename: Burcin
authors.initials: B
authors.lastname: Ekser
authors.forename: Bruno
authors.initials: B
authors.lastname: Gridelli
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Veroux
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001792:Blood Platelets / Q000378:metabolism; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism; D006084:Graft Rejection; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000378:metabolism; D010215:Papio; D013552:Swine; D013921:Thrombocytopenia / Q000209:etiology; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D018958:CD55 Antigens; D051916:Membrane Cofactor Protein