Nature Communications (Apr 2024)
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,
- Paige M. Porrett
Affiliations
- Matthew D. Cheung
- Department of Surgery, University of Alabama at Birmingham
- Rebecca Asiimwe
- Department of Surgery, University of Alabama at Birmingham
- Elise N. Erman
- Department of Surgery, University of Alabama at Birmingham
- Christopher F. Fucile
- Informatics Institute, University of Alabama at Birmingham
- Shanrun Liu
- Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham
- Chiao-Wang Sun
- Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham
- Vidya Sagar Hanumanthu
- Flow Cytometry & Single Cell Core Facility, University of Alabama at Birmingham
- Harish C. Pal
- Flow Cytometry & Single Cell Core Facility, University of Alabama at Birmingham
- Emma D. Wright
- Department of Surgery, University of Alabama at Birmingham
- Gelare Ghajar-Rahimi
- Department of Surgery, University of Alabama at Birmingham
- Daniel Epstein
- Department of Surgery, University of Alabama at Birmingham
- Babak J. Orandi
- Department of Surgery, University of Alabama at Birmingham
- Vineeta Kumar
- Department of Medicine, University of Alabama at Birmingham
- Douglas J. Anderson
- Department of Surgery, University of Alabama at Birmingham
- Morgan E. Greene
- Department of Surgery, University of Alabama at Birmingham
- Markayla Bell
- Department of Surgery, University of Alabama at Birmingham
- Stefani Yates
- Department of Surgery, University of Alabama at Birmingham
- Kyle H. Moore
- Department of Medicine, University of Alabama at Birmingham
- Jennifer LaFontaine
- Department of Surgery, University of Alabama at Birmingham
- John T. Killian
- Department of Surgery, University of Alabama at Birmingham
- Gavin Baker
- Department of Surgery, University of Alabama at Birmingham
- Jackson Perry
- Department of Surgery, University of Alabama at Birmingham
- Zayd Khan
- Department of Surgery, University of Alabama at Birmingham
- Rhiannon Reed
- Department of Surgery, University of Alabama at Birmingham
- Shawn C. Little
- Department of Surgery, University of Alabama at Birmingham
- Alexander F. Rosenberg
- Informatics Institute, University of Alabama at Birmingham
- James F. George
- Department of Surgery, University of Alabama at Birmingham
- Jayme E. Locke
- Department of Surgery, University of Alabama at Birmingham
- Paige M. Porrett
- Department of Surgery, University of Alabama at Birmingham
- DOI
- https://doi.org/10.1038/s41467-024-47454-7
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
