Since the first attempt in 1968, survival following pig-to-primate liver xenotransplantation (LXT) has been limited. We evaluated a model utilizing α-1,3-galactosyltransferase knockout donors, continuous post-transplant infusion of human prothrombin concentrate complex and immunosuppression including anti-thymocyte globulin, FK-506, methylprednisone and co-stimulation blockade (belatacept, n=3 or anti-CD40mAb, n=1) to extend survival. Baboon #1 remained well until POD25 when euthanasia was required due to cholestasis and plantar ulcers. Baboon #2 was euthanized following a seizure on POD5, despite normal LFTs and no apparent pathology. Baboon # 3 demonstrated initial stable liver function, but was euthanized on POD8 due to worsening LFTs. Pathology revealed C4d positivity, extensive hemorrhagic necrosis and a focal CMV inclusion. Baboon # 4 was clinically well with stable LFTs until POD29, when euthanasia was again necessitated by plantar ulcerations as well as rising LFTs. Final pathology was C4d negative and without evidence of rejection, inflammation or TMA. Thus, nearly one-month rejection-free survival has been achieved following LXT in 2 of 4 continuous recipients, demonstrating that the porcine liver can support life in primates for several weeks and is encouraging for potential clinical application of LXT as a bridge to allotransplantation for patients with acute-on-chronic or fulminant hepatic failure.

To our knowledge, this is the first evidence of histologically viable porcine lung grafts beyond 7 days in baboons. Our results indicate that GalT-KO pig lungs are highly susceptible to acute humoral rejection and that this may be mitigated by transgenic expression of hCD47.

Purpose of Review There continues to be 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 has been limited to 9 days, initially due to hyperacute rejection which has been ameliorated through use of genetically engineered donor organs, but ultimately due to profound thrombocytopenia, thrombotic microangiopathy (TMA), and bleeding. More recently, demise secondary to lethal coagulopathy was avoided with LXT of α(1,3)-galactosyltransferase (GT) knockout (GTKO), CMV-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 two 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.