Medical, surgical and technological advancements in organ transplantation continue to expand life-saving treatment options for patients with end-stage lung disease, but transplantation remains limited by the low availability of donor organs. As chronic respiratory disease is the third-leading cause of death worldwide1, the need for innovative solutions to reduce associated morbidity and mortality is imperative. In 2020, lung transplantation remains the only definitive cure for end-stage lung disease, which has poor prognosis due to disease severity, insufficient donor lung availability and high rates of chronic allograft dysfunction. Strategies to increase organ supply involve utilizing extended criteria lungs, developing new technologies to recover donor lungs for transplantation and generating transplantable organs from xenogeneic sources, such as genetically engineered swine. Currently, the most utilized approach is to recover standard and extended criteria lungs by normothermic EVLP9. However, evidence of cellular regeneration in injured human lungs has not been robustly demonstrated in EVLP studies. To increase the quality and duration of extracorporeal lung support and investigate the potential for cellular regeneration, our group previously reported the development of an organ support platform in a swine model. While EVLP of healthy swine lungs perfused with whole blood has been reported, a study of injured swine lungs placed on EVLP with whole blood demonstrated insufficient recovery and resulted in impaired oxygenation and poor performance after transplantation13. In contrast, cross-circulation of severely injured swine lungs with a swine host enabled substantial cellular regeneration and functional recovery. Unlike EVLP systems, cross-circulation provides extracorporeal lungs with complete systemic support, including hepatic, pancreatic, renal and neurohormonal regulation, thereby enabling robust maintenance of healthy lungs outside the body for 4d… Continue reading.