Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs

Ahmed E. Hozain, John D. O’Neill, Meghan R. Pinezich, Yuliya Tipograf, Rachel Donocoff, Katherine M. Cunningham, Andrew Tumen, Kenmond Fung, Rei Ukita, Michael T. Simpson, Jonathan A. Reimer, Edward C. Ruiz, Dawn Queen, John W. Stokes, Nancy L. Cardwell, Jennifer Talackine, Jinho Kim, Hans Willem Snoeck, Ya Wen Chen, Alexander RomanovCharles C. Marboe, Adam D. Griesemer, Brandon A. Guenthart, Matthew Bacchetta, Gordana Vunjak-Novakovic

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1102-1113
Number of pages12
JournalNature Medicine
Volume26
Issue number7
DOIs
StatePublished - 1 Jul 2020

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