Current opinion in organ transplantation · 2017
Liver xenotransplantation.
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Patel Madhukar S, Louras Nathan, Vagefi Parsia A
Аннотация
PURPOSE OF REVIEW: There continues to be an inadequate organ supply and lack of effective temporary support, for patients with liver failure. The purpose of this review is to discuss recent progress in the field of orthotopic pig-to-nonhuman primate (NHP) liver xenotransplantation (LXT).
RECENT FINDINGS: From 1968 to 2012, survival in pig-to-NHP LXT was limited to 9 days, initially due to hyperacute rejection which has been ameliorated through use of genetically engineered donor organs, but ultimately because of profound thrombocytopenia, thrombotic microangiopathy, and bleeding. Most recently, however, demise secondary to lethal coagulopathy has been avoided with LXT of α(1,3)-galactosyltransferase knockouts and cytomegalovirus-negative porcine xenografts into baboons receiving exogenous administration of coagulation factors and co-stimulation blockade, establishing that a porcine liver is capable of supporting NHP life for nearly a month.
SUMMARY: Continued consistent achievement of pig-to-NHP LXT survival beyond 2 weeks justifies consideration of a clinical application as a bridge to allotransplantation for patients with acute hepatic failure. Further genetic modifications to the donor, as well as additional studies, are required in order to apply LXT as destination therapy.
RECENT FINDINGS: From 1968 to 2012, survival in pig-to-NHP LXT was limited to 9 days, initially due to hyperacute rejection which has been ameliorated through use of genetically engineered donor organs, but ultimately because of profound thrombocytopenia, thrombotic microangiopathy, and bleeding. Most recently, however, demise secondary to lethal coagulopathy has been avoided with LXT of α(1,3)-galactosyltransferase knockouts and cytomegalovirus-negative porcine xenografts into baboons receiving exogenous administration of coagulation factors and co-stimulation blockade, establishing that a porcine liver is capable of supporting NHP life for nearly a month.
SUMMARY: Continued consistent achievement of pig-to-NHP LXT survival beyond 2 weeks justifies consideration of a clinical application as a bridge to allotransplantation for patients with acute hepatic failure. Further genetic modifications to the donor, as well as additional studies, are required in order to apply LXT as destination therapy.