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GalT‐ KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD 47 on porcine blood vessels
Author(s) -
Watanabe Hironosuke,
Sahara Hisashi,
Nomura Shunichiro,
Tanabe Tatsu,
EkanayakeAlper Dilrukshi K.,
Boyd Lennan K.,
Louras Nathan J.,
Asfour Arsenoi,
Danton Makenzie A.,
Ho SiuHong,
Arn Scott J.,
Hawley Robert J.,
Shimizu Akira,
Nagayasu Takeshi,
Ayares David,
Lorber Marc I.,
Sykes Megan,
Sachs David H.,
Yamada Kazuhiko
Publication year - 2018
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12391
Subject(s) - baboon , xenotransplantation , lung , medicine , transplantation , andrology , lung transplantation , pathology
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 ( XLT x). Methods Eleven baboons received genetically modified porcine left lungs from either GalT‐ KO alone (n = 3), GalT‐ KO /human CD 47( hCD 47)/ hCD 55 (n = 3), GalT‐ KO / hD 47/ hCD 46 (n = 4), or GalT‐ KO / hCD 39/ hCD 46/ hCD 55/ TBM / EPCR (n = 1) swine. The first 2 XLT x 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. hCD 47 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 hCD 47 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 hCD 47.