*Purpose: Cardiac xenotransplantation has been proposed to bridge the gap in organ shortage for those in end-stage heart failure without the opportunity to receive a heart. Recently, it has been shown that survival of a non-human primate recipient with a genetically engineered (GE) porcine- cardiac xenograft can be achieved up to 6 months in the orthotopic position with the addition of temsirolimus, blood pressure and heart rate control. We investigate an alternative means to achieve long-term survival, without the use of these adjuncts. We used “Multi-gene” edited pigs as xenograft donors with the addition of multiple human transgenes for complement regulation, thromboregulation, anti-inflammation and growth.

*Methods: Baboons weighing 15-30 kg were used as recipients for life supporting cardiac xenografts. Weight-matched swine with multi-gene constructs were used as donors (table 1). Cardiac preservation was performed using an XVIVO© Perfusion system with XHS blood cardioplegia induction. Recipient blood pressure and heart rate were not controlled and temsirolimus was not administered after transplantation.

*Results: Group 1 xenografts functioned well between 84-95 days, but ultimately succumbed to antibody mediated rejection and diastolic heart failure. Group 2 xenografts functioned well over 6 months. One was electively euthanized on post-transplant day #182 for histologic examination. The second recipient underwent an endomyocardial biopsy on post-transplant day #220, with survival ongoing greater than 240 days exhibiting excellent graft function. Both demonstrated normal histology without evidence of rejection.

*Conclusions: Xenografts with multiple transgenes and knockouts produce durable long-term survival and demonstrate pre-clinical efficacy to pursue the first human clinical trials. Consideration should be those with CMAHKO and GHRKO.

« Back to 2021 American Transplant Congress