Spatiotemporal immune atlas of a clinical-grade gene-edited pig-to-human kidney xenotransplant

Matthew D. Cheung, Rebecca Asiimwe, Elise N. Erman, Christopher F. Fucile, Shanrun Liu, Chiao-Wang Sun, Vidya Sagar Hanumanthu, Harish C. Pal, Emma D. Wright, Gelare Ghajar-Rahimi, Daniel Epstein, Babak J. Orandi, Vineeta Kumar, Douglas J. Anderson, Morgan E. Greene, Markayla Bell, Stefani Yates, Kyle H. Moore, Jennifer LaFontaine, John T. Killian, Gavin Baker, Jackson Perry, Zayd Khan, Rhiannon Reed, Shawn C. Little, Alexander F. Rosenberg, James F. George, Jayme E. Locke and Paige M. Porrett ()
Additional contact information
Matthew D. Cheung: University of Alabama at Birmingham
Rebecca Asiimwe: University of Alabama at Birmingham
Elise N. Erman: University of Alabama at Birmingham
Christopher F. Fucile: University of Alabama at Birmingham
Shanrun Liu: University of Alabama at Birmingham
Chiao-Wang Sun: University of Alabama at Birmingham
Vidya Sagar Hanumanthu: University of Alabama at Birmingham
Harish C. Pal: University of Alabama at Birmingham
Emma D. Wright: University of Alabama at Birmingham
Gelare Ghajar-Rahimi: University of Alabama at Birmingham
Daniel Epstein: University of Alabama at Birmingham
Babak J. Orandi: University of Alabama at Birmingham
Vineeta Kumar: University of Alabama at Birmingham
Douglas J. Anderson: University of Alabama at Birmingham
Morgan E. Greene: University of Alabama at Birmingham
Markayla Bell: University of Alabama at Birmingham
Stefani Yates: University of Alabama at Birmingham
Kyle H. Moore: University of Alabama at Birmingham
Jennifer LaFontaine: University of Alabama at Birmingham
John T. Killian: University of Alabama at Birmingham
Gavin Baker: University of Alabama at Birmingham
Jackson Perry: University of Alabama at Birmingham
Zayd Khan: University of Alabama at Birmingham
Rhiannon Reed: University of Alabama at Birmingham
Shawn C. Little: University of Alabama at Birmingham
Alexander F. Rosenberg: University of Alabama at Birmingham
James F. George: University of Alabama at Birmingham
Jayme E. Locke: University of Alabama at Birmingham
Paige M. Porrett: University of Alabama at Birmingham

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. Here, we transplant a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and study the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells are uncommon in the porcine kidney cortex early after xenotransplantation and consist of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages express genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft is detectable. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression may be able to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

Date: 2024
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DOI: 10.1038/s41467-024-47454-7

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