Genetically Modified Porcine-to-Human Cardiac Xenotransplantation

This brief report details the first successful transplantation of a genetically modified pig heart into a 57-year-old man with end-stage nonischemic cardiomyopathy, who was ineligible for human heart transplantation. The pig heart, engineered with 10 gene edits to mitigate immune rejection (including inactivation of GGTA1 and introduction of human genes like CD46 and THBD), functioned normally for 49 days before sudden diastolic failure occurred. Immunosuppression involved CD40 blockade, B-cell depletion, and complement inhibition. Despite initial success, the graft eventually failed due to unexplained myocardial thickening and necrosis, without typical rejection pathology. Postmortem analysis revealed interstitial edema and vascular damage. The case highlights advancements in xenotransplantation while underscoring unresolved challenges, such as zoonotic risks (e.g., porcine cytomegalovirus) and graft durability.

This brief report details the first successful transplantation of a genetically modified pig heart into a 57-year-old man with end-stage nonischemic cardiomyopathy, who was ineligible for human heart transplantation. The pig heart, engineered with 10 gene edits to mitigate immune rejection (including inactivation of GGTA1 and introduction of human genes like CD46 and THBD), functioned normally for 49 days before sudden diastolic failure occurred. Immunosuppression involved CD40 blockade, B-cell depletion, and complement inhibition. Despite initial success, the graft eventually failed due to unexplained myocardial thickening and necrosis, without typical rejection pathology. Postmortem analysis revealed interstitial edema and vascular damage. The case highlights advancements in xenotransplantation while underscoring unresolved challenges, such as zoonotic risks (e.g., porcine cytomegalovirus) and graft durability.