Attenuation of hyperacute dysfunction and coagulopathy in GalT-KO pulmonary xenotransplantation

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The results of both heart and kidney GalT-KO swine-to-primate studies have been more encouraging than for lung xenotransplantation. This may be because research in pulmonary xenotransplantation is limited. Here, we evaluated 1) whether GalT-KO lungs could prevent hyper-acute pulmonary xenograft dysfunction using ex-vivo lung perfusion or in-vivo orthotopic left lung transplant model and 2) the effect of carbon monoxide (CO) on reducing the development of microangiopathy (CO-treated animals). GalT-KO lungs exhibited stable pulmonary function compared with wild-type lungs when perfused with human blood in an ex-vivo perfusion model, which was confirmed by the in-vivo transplant model. Although, thrombotic microangiopathy ultimately developed in all grafts of the CO-treated animals, the degree of microangiopathy was reduced in these animals. Reduction of the innate immune response by CO treatment would be one of the therapeutic strategies for prolonging pulmonary xenograft survival.