GalT‐KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD47 on porcine blood vessels. (12th March 2018)

• Record Type: Journal Article
• Authors: Watanabe, Hironosuke; Sahara, Hisashi; Nomura, Shunichiro; Tanabe, Tatsu; Ekanayake‐Alper, Dilrukshi K.; Boyd, Lennan K.; Louras, Nathan J.; Asfour, Arsenoi; Danton, Makenzie A.; Ho, Siu‐Hong; Arn, Scott J.; Hawley, Robert J.; Shimizu, Akira; Nagayasu, Takeshi; Ayares, David; Lorber, Marc I.; Sykes, Megan; Sachs, David H.; Yamada, Kazuhiko
• Is Part Of: Xenotransplantation. Volume 25:Number 5(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-03-12
• Subjects: hCD47 -- lung transplantation -- pig to baboon -- xenotransplantation; Xenografts -- Periodicals; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/xen.12391
• Languages: English
• ISSNs: 0908-665X

Abstract

Abstract: Background: Despite recent progress in survival times of xenografts in non‐human primates, there are no reports of survival beyond 5 days of histologically well‐aerated porcine lung grafts in baboons. Here, we report our initial results of pig‐to‐baboon xeno‐lung transplantation (XLTx). Methods: Eleven baboons received genetically modified porcine left lungs from either GalT‐KO alone (n = 3), GalT‐KO/humanCD47(hCD47)/hCD55 (n = 3), GalT‐KO/hD47/hCD46 (n = 4), or GalT‐KO/hCD39/hCD46/hCD55/TBM/EPCR (n = 1) swine. The first 2 XLTx procedures were performed under a non‐survival protocol that allowed a 72‐hour follow‐up of the recipients with general anesthesia, while the remaining 9 underwent a survival protocol with the intention of weaning from ventilation. Results: Lung graft survivals in the 2 non‐survival animals were 48 and >72 hours, while survivals in the other 9 were 25 and 28 hours, at 5, 5, 6, 7, >7, 9, and 10 days. One baboon with graft survival >7 days, whose entire lung graft remained well aerated, was euthanized on POD 7 due to malfunction of femoral catheters. hCD47 expression of donor lungs was detected in both alveoli and vessels only in the 3 grafts surviving >7, 9, and 10 days. All other grafts lacked hCD47 expression in endothelial cells and were completely rejected with diffuse hemorrhagic changes and antibody/complement deposition detected in association with early graft loss. Conclusions: To our knowledge, this is the first evidence of histologically viable porcine lung grafts beyond 7 days in baboons. Our results indicate that GalT‐KO pig lungs are highly susceptible to acute humoral rejection and that this may be mitigated by transgenic expression of hCD47.