Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs
Daniel Eisenson, Yu Hisadome, Michelle Santillan, Hayato Iwase, Wei‐Li Chen, Akira Shimizu, Alex Schulick, Du Gu, Armaan F. Akbar, Alice L. Zhou, Kristy Koenig, Kasinath Kuravi, Farzana Rahman, Lori Sorrells, Lars Burdorf, Kristina DeSmet, Daniel Warren, Leigh Peterson, Marc I. Lorber, David Ayares, Andrew M. Cameron, Kazuhiko Yamada
Abstract
Xenotransplantation represents a possible solution to the organ shortage crisis and is an imminent clinical reality with long-term xenograft survival in pig-to-nonhuman primate (NHP) heart and kidney large animal models, and short-term success in recent human decedent and clinical studies. However, concerns remain about safe clinical translation of these results, given the inconsistency in published survival as well as key differences between preclinical procurement and immunosuppression and clinical standards-of-care. Notably, no studies of solid organ pig-to-NHP transplantation have achieved xenograft survival longer than one month without CD40/CD154 costimulatory blockade, which is not currently an FDA-approved immunosuppression strategy. We now present consistent survival in consecutive cases of pig-to-NHP kidney xenotransplantation, including long-term survival after >3 hours of xenograft cold preservation time as well as long-term survival using FDA-approved immunosuppression. These data provide critical supporting evidence for the safety and feasibility of clinical kidney xenotransplantation. Moreover, long-term survival without CD40/CD154 costimulatory blockade may provide important insights for immunosuppression regimens to be considered for first-in-human clinical trials.