title: Which anti-platelet therapies might be beneficial in xenotransplantation?
abstract: Xenotransplantation could provide an unlimited and elective supply of grafts, once mechanisms of graft loss and vascular injury are better understood. The development of α-1,3-galactosyltransferase gene-knockout (GalT-KO) swine with the removal of a dominant xeno-antigen has been an important advance; however, delayed xenograft and acute vascular reaction in GalT-KO animals persist. These occur, at least in part, because of humoral reactions that result in vascular injury. Intrinsic molecular incompatibilities in the regulation of blood clotting and extracellular nucleotide homeostasis between discordant species may also predispose to thrombophilia within the vasculature of xenografts. Although limited benefits have been achieved with currently available pharmacological anti-thrombotics and anti-coagulants, the highly complex mechanisms of platelet activation and thrombosis in xenograft rejection also require potent immunosuppressive interventions. We will focus on recent thromboregulatory approaches while elucidating appropriate anti-platelet mechanisms. We will discuss potential benefits of additional anti-thrombotic interventions that are possible in transgenic swine and review recent developments in pharmacological anti-platelet therapy.
authors.affiliation: Liver Center and Transplantation Institute, Department of Medicine and Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. mschmelz@bidmc.harvard.edu
authors.forename: Moritz
authors.initials: M
authors.lastname: Schmelzle
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cowan
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D005700:Galactosyltransferases / Q000235:genetics / Q000502:physiology; D055786:Gene Knockout Techniques; D006084:Graft Rejection / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D015539:Platelet Activation / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013552:Swine; D013927:Thrombosis / Q000503:physiopathology; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D005700:Galactosyltransferases; C530267:alpha-1,3-galactosyltransferase 1, porcine