Cardiac xenotransplantation: From imagination to achievable practice

Table 2 Comparative summary of the human clinical evidence in cardiac xenotransplantation

Case	Evidence model	Donor genotype	Preservation strategy	Immunosuppression	Follow-up duration	Dominant complications	Key limitations	Ref.
University of Maryland, January 2022	Living compassionate-use recipient	10-gene-edited pig (GGTA1/CMAH/B4GALNT2 knockout, GHR knockout; hCD46, hCD55, hTBM, hEPCR, hCD47, hHMOX1 transgenes)	Not fully reported in the primary publication	Investigational anti-CD40 costimulation blockade combined with mycophenolate mofetil and corticosteroids	60 days (recipient died on POD 60)	Progressive diastolic dysfunction from POD 47; capillary injury with complement deposition; PCMV/PRV reactivation within the graft; IVIG-associated rise in anti-pig IgG	Single compassionate-use case; non-approved investigational agents; latent donor viral infection missed by conventional screening; mechanism of graft failure multifactorial and incompletely resolved	[14,15]
University of Maryland, September 2023	Living compassionate-use recipient	10-gene-edited pig (same editing platform)	Not fully reported	Costimulation blockade with intensified complement-directed therapy	Approximately 40 days (died October 30, 2023)	Early antibody-mediated rejection on biopsy at 2 weeks; subsequent anti-pig antibody surge with progressive graft injury and renal failure	Single compassionate-use case; antibody-mediated rejection emerged despite a healthier recipient, enhanced donor screening, and complement inhibition	[16,17]
NYU Langone, 2022 (two cases)	Deceased (brain-dead) recipient research model	10-gene-edited pig	Standard clinical procurement and preservation	Conventional allotransplant-style immunosuppression without investigational agents	Protocol-defined observation period of 66 hours (not patient survival)	Functional decline in one graft attributed to donor-recipient size mismatch; no rejection and no zoonotic transmission observed	Very short observation window; brain-death physiology does not model living recipients; cannot inform on long-term survival, chronic rejection, or infection risk	[18]

POD: Postoperative day; PCMV/PRV: Porcine cytomegalovirus/porcine roseolovirus; IVIG: Intravenous immunoglobulin; GHR: Growth hormone receptor; hTBM: Human thrombomodulin; hEPCR: Human endothelial protein C receptor; hHMOX1: Human heme oxygenase-1; NYU: New York University.