Pig-to-non-human primate heart transplantation: the final step toward clinical xenotransplantation?

Abstract Background The demand for donated human hearts far exceeds the number available. Xenotransplantation of genetically modified porcine organs provides an alternative. In 2000, an Advisory Board of the International Society for Heart and Lung Transplantation (ISHLT) set the benchmark for commencing clinical cardiac xenotransplantation as consistent 60% survival of non-human primates after life-supporting porcine heart transplantations. Recently, we reported the stepwise optimization of pig-to-baboon orthotopic cardiac xenotransplantation, finally resulting in consistent success with four recipients surviving 90 (n = 2), 182 and 195 days. Here we report on four additional recipients, supporting the efficacy of our procedure. Results The first two additional recipients succumbed to porcine CMV (PCMV) infections on days 15 and 27, respectively. In two further experiments, PCMV infections were successfully avoided, and three months survival was achieved. Throughout all long-term experiments, heart, liver and renal functions remained within normal ranges. Post-mortem cardiac diameters were slightly increased when compared to the time of transplantation, but with no detrimental effect. There were no signs of thrombotic microangiopathy. The current regimen enabled the prolonged survival and function of orthotopic cardiac xenografts in altogether six out of eight baboons, of which four were now added. These results exceed the threshold set by the ISHLT Advisory Board. Conclusions The results of our current and prior experimental cardiac xenotransplantations together fulfill for the first time the preclinical efficacy suggestions. PCMV-positive donor animals must be avoided.