GalT‐<scp>KO</scp> pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of <scp>hCD</scp>47 on porcine blood vessels

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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 (<jats:styled-content style="fixed-case">XLT</jats:styled-content>x).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Eleven baboons received genetically modified porcine left lungs from either GalT‐<jats:styled-content style="fixed-case">KO</jats:styled-content> alone (n = 3), GalT‐<jats:styled-content style="fixed-case">KO</jats:styled-content>/human<jats:styled-content style="fixed-case">CD</jats:styled-content>47(<jats:styled-content style="fixed-case">hCD</jats:styled-content>47)/<jats:styled-content style="fixed-case">hCD</jats:styled-content>55 (n = 3), GalT‐<jats:styled-content style="fixed-case">KO</jats:styled-content>/<jats:styled-content style="fixed-case">hD</jats:styled-content>47/<jats:styled-content style="fixed-case">hCD</jats:styled-content>46 (n = 4), or GalT‐<jats:styled-content style="fixed-case">KO</jats:styled-content>/<jats:styled-content style="fixed-case">hCD</jats:styled-content>39/<jats:styled-content style="fixed-case">hCD</jats:styled-content>46/<jats:styled-content style="fixed-case">hCD</jats:styled-content>55/<jats:styled-content style="fixed-case">TBM</jats:styled-content>/<jats:styled-content style="fixed-case">EPCR</jats:styled-content> (n = 1) swine. The first 2 <jats:styled-content style="fixed-case">XLT</jats:styled-content>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 <jats:styled-content style="fixed-case">POD</jats:styled-content> 7 due to malfunction of femoral catheters. <jats:styled-content style="fixed-case">hCD</jats:styled-content>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 <jats:styled-content style="fixed-case">hCD</jats:styled-content>47 expression in endothelial cells and were completely rejected with diffuse hemorrhagic changes and antibody/complement deposition detected in association with early graft loss.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>To our knowledge, this is the first evidence of histologically viable porcine lung grafts beyond 7 days in baboons. Our results indicate that GalT‐<jats:styled-content style="fixed-case">KO</jats:styled-content> pig lungs are highly susceptible to acute humoral rejection and that this may be mitigated by transgenic expression of <jats:styled-content style="fixed-case">hCD</jats:styled-content>47.</jats:p></jats:sec>