Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs.
Ahmed E HozainJohn D O'NeillMeghan R PinezichYuliya TipografRachel DonocoffKatherine M CunninghamAndrew TumenKenmond FungRei UkitaMichael T SimpsonJonathan A ReimerEdward C RuizDawn QueenJohn W StokesNancy L CardwellJennifer TalackineJinho KimHans-Willem SnoeckYa-Wen ChenAlexander RomanovCharles C MarboeAdam D GriesemerBrandon A GuenthartMatthew D BacchettaGordana Vunjak-NovakovicPublished in: Nature medicine (2020)
Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24 h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering.
Keyphrases
- endothelial cells
- induced pluripotent stem cells
- pluripotent stem cells
- end stage renal disease
- cardiovascular disease
- newly diagnosed
- chronic kidney disease
- magnetic resonance imaging
- stem cells
- high throughput
- computed tomography
- bone marrow
- magnetic resonance
- extracorporeal membrane oxygenation
- ejection fraction
- risk factors
- peritoneal dialysis
- drug induced