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

Authors :
Cheung MD
Asiimwe R
Erman EN
Fucile CF
Liu S
Sun CW
Hanumanthu VS
Pal HC
Wright ED
Ghajar-Rahimi G
Epstein D
Orandi BJ
Kumar V
Anderson DJ
Greene ME
Bell M
Yates S
Moore KH
LaFontaine J
Killian JT Jr
Baker G
Perry J
Khan Z
Reed R
Little SC
Rosenberg AF
George JF
Locke JE
Porrett PM
Source :
Nature communications [Nat Commun] 2024 Apr 11; Vol. 15 (1), pp. 3140. Date of Electronic Publication: 2024 Apr 11.
Publication Year :
2024

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.<br /> (© 2024. The Author(s).)

Details

Language :
English
ISSN :
2041-1723
Volume :
15
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
38605083
Full Text :
https://doi.org/10.1038/s41467-024-47454-7