Consistent Success in Life-supporting Porcine Cardiac Xenotransplantation

Primates receiving heart transplants from genetically engineered pigs have survived more than six months, a new study reveals.

Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. The results reported in the article show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure the long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. A consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation. The study, in which four baboons lived in good health for several months after surgery, brings xenotransplantation one step closer to the clinic,