Session Time: 6:00pm-7:00pm
Presentation Time: 6:05pm-6:10pm
*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.
To cite this abstract in AMA style:Goerlich C, Griffith B, Singh A, Zhang T, Tatarov I, Lewis B, Sentz F, Hershfeld A, Odonkor P, Williams B, Strauss E, Tabatabai A, Bhutta A, Ayares D, Kaczorowski D, Mohiuddin M. Life-supporting Multi-gene Cardiac Xenografts From Swine Demonstrate Survival >8 Months and Preclinical Efficacy for Human Clinical Trials [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/life-supporting-multi-gene-cardiac-xenografts-from-swine-demonstrate-survival-8-months-and-preclinical-efficacy-for-human-clinical-trials/. Accessed September 24, 2021.
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