Pig-to-human lung xenotransplantation into a brain-dead recipient

Abstract

Genetically engineered pig lungs have not previously been transplanted into humans, leaving key questions unanswered regarding the human immune response in the context of a xenotransplanted lung and the possibility of hyperacute rejection. Here, we report a case of pig-to-human lung xenotransplantation, in which a lung from a six-gene-edited pig was transplanted into a 39-year-old brain-dead male human recipient following a brain hemorrhage. The lung xenograft maintained viability and functionality over the course of the 216 hours of the monitoring period, without signs of hyperacute rejection or infection. Severe edema resembling primary graft dysfunction was observed at 24 hours after transplantation, potentially due to ischemia-reperfusion injury. Antibody-mediated rejection appeared to contribute to xenograft damage on postoperative days 3 and 6, with partial recovery by day 9. Immunosuppression included rabbit anti-thymocyte globulin, basiliximab, rituximab, eculizumab, tofacitinib, tacrolimus, mycophenolate mofetil and tapering steroids, with adjustments made during the postoperative period based on assessments of immune status. Although this study demonstrates the feasibility of pig-to-human lung xenotransplantation, substantial challenges relating to organ rejection and infection remain, and further preclinical studies are necessary before clinical translation of this procedure.