Gene-edited pig cardiac xenotransplantation as a bridge to allotransplantation in infants: Progress in a pig-to-baboon model.

Gene-edited pig hearts may have an application for critically ill infants who are poor candidates for mechanical support. We established a pediatric animal model of gene-edited pig orthotopic cardiac xenotransplantation (OCXT) in baboons to assess its potential as a bridge to allotransplantation. Fifteen OCXTs were performed from genetically-engineered infantile pigs into size-matched baboons. Maintenance immunosuppression was founded on CD40/CD154 costimulation pathway blockade and rapamycin. After being sustained by xenografts for >4 months, 3 xenograft recipients were selected for transition to cardiac allotransplantation. Outcomes were tracked by invasive hemodynamic monitoring, surface echocardiography, and serial blood tests. After OCXT, 8 of 15 (53%) baboons achieved survival of >1 month, with 6 surviving for >3 months. Mortality was more common early in the study, followed by longer and more uniform survival later. The longest survivor lived >24 months postxenotransplantation. There has been no evidence of significant xeno- or allo-sensitization during xenograft support. The aims of these studies were (1) to demonstrate that a gene-edited pig heart can confer months-long survival in pediatric-sized recipient baboons, and (2) to determine whether prolonged xenograft exposure does not preclude subsequent allotransplantation. Our data suggest that these aims may be achievable and warrant further study.