P245

9-day survival and control of thrombocytopenia following liver xenotransplantation in baboons using GalT-KO swine grafts

Christian Schuetz¹, Karen Kim¹, Nahel Elias¹, Gregory Veillette¹, Isaac Wamala¹, Rex Smith², Simon Robson³, Benedict Cosimi¹, David Sachs¹, Martin Hertl¹

Departments of ¹Surgery and ²Pathology, Massachusetts General Hospital; ³Gastroenterology, Beth Israel Deaconess Hospital; Boston, MA, United States

Despite recent progress in stem cell research and tissue engineering, xenotransplantation remains the best near-term hope for satisfying the critical limitation imposed on the field of liver transplantation by the severe shortage of cadaveric allogeneic organs. The recent production of alpha1,3-galactosyl transferase knockout (GalT-KO) miniature swine has made it possible to evaluate xenotransplantation of pig livers in a clinically relevant pig-to-non-human primate model in the absence of natural anti-Gal antibodies. Here we report our initial experiences with GalT-KO liver transplants in baboons in order to evaluate their potential advantage over liver transplants from standard miniature swine utilized previously, for which maximum survivals of only 3 days were achieved. The first of our recipient baboons suffered from systemic hypoxia, alkalosis and pulmonary edema postoperatively which impacted the graft and resulted in subnormal hepatic function. The second recipients xenogenic liver graft functioned normally. Nevertheless both animals exhibited severe Thrombocytopenia requiring massive transfusion of Red blood cells. We were able to maintain the platelet count at over 40,000/mm ³ leading to a survival period of 9 days, the longest reported survival of a pig-to-primate liver transplant to date. There were no signs of rejection or hepatic failure in the second recipient. Nevertheless, the ultimately lethal coagulopathy observed in this recipient, despite control of thrombocytopenia, suggests that additional causes of coagulation disorders in this model will still need to be addressed.