Genetically Modified Porcine-to-Human Cardiac Xenotransplantation

TLDR

The study aims to identify mechanisms underlying post‑transplant complications. A genetically modified pig heart with ten gene edits was transplanted into a 57‑year‑old patient on ECMO, with CD40‑based immunosuppression. The graft functioned initially but failed abruptly on day 49 with edema, necrosis, and no evidence of rejection, leading to death on day 60. Funding was provided by the University of Maryland Medical Center and School of Medicine.

Abstract

A 57-year-old man with nonischemic cardiomyopathy who was dependent on venoarterial extracorporeal membrane oxygenation (ECMO) and was not a candidate for standard therapeutics, including a traditional allograft, received a heart from a genetically modified pig source animal that had 10 individual gene edits. Immunosuppression was based on CD40 blockade. The patient was weaned from ECMO, and the xenograft functioned normally without apparent rejection. Sudden diastolic thickening and failure of the xenograft occurred on day 49 after transplantation, and life support was withdrawn on day 60. On autopsy, the xenograft was found to be edematous, having nearly doubled in weight. Histologic examination revealed scattered myocyte necrosis, interstitial edema, and red-cell extravasation, without evidence of microvascular thrombosis - findings that were not consistent with typical rejection. Studies are under way to identify the mechanisms responsible for these changes. (Funded by the University of Maryland Medical Center and School of Medicine.).