Immune characterization of a xenogeneic human lung cross-circulation support system

Improved approaches to expanding the pool of donor lungs suitable for transplantation are critically needed for the growing population with end-stage lung disease. Cross-circulation (XC) of whole blood between swine and explanted human lungs has previously been reported to enable the extracorporeal...

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Bibliographic Details
Published in:Science advances 2023-03, Vol.9 (13), p.eade7647-eade7647
Main Authors: Wu, Wei K, Stier, Matthew T, Stokes, John W, Ukita, Rei, Patel, Yatrik J, Cortelli, Michael, Landstreet, Stuart R, Talackine, Jennifer R, Cardwell, Nancy L, Simonds, Elizabeth M, Mentz, Meredith, Lowe, Cindy, Benson, Clayne, Demarest, Caitlin T, Alexopoulos, Sophoclis P, Shaver, Ciara M, Bacchetta, Matthew
Format: Article
Language:English
Subjects:
Animals
Biomedicine and Life Sciences
Health and Medicine
Humans
Immunosuppression Therapy
Lung
Lung Transplantation
SciAdv r-articles
Swine
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Summary:Improved approaches to expanding the pool of donor lungs suitable for transplantation are critically needed for the growing population with end-stage lung disease. Cross-circulation (XC) of whole blood between swine and explanted human lungs has previously been reported to enable the extracorporeal recovery of donor lungs that declined for transplantation due to acute, reversible injuries. However, immunologic interactions of this xenogeneic platform have not been characterized, thus limiting potential translational applications. Using flow cytometry and immunohistochemistry, we demonstrate that porcine immune cell and immunoglobulin infiltration occurs in this xenogeneic XC system, in the context of calcineurin-based immunosuppression and complement depletion. Despite this, xenogeneic XC supported the viability, tissue integrity, and physiologic improvement of human donor lungs over 24 hours of xeno-support. These findings provide targets for future immunomodulatory strategies to minimize immunologic interactions on this organ support biotechnology.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.ade7647