Spatiotemporal immune atlas of the first clinical-grade, gene-edited pig-to-human kidney xenotransplant

Autor: Paige Porrett, Matthew Cheung, Rebecca Asiimwe, Elise Erman, Christopher Fucile, Shanrun Liu, Chiao-Wang Sun, Vidya Hanumanthu, Harish Pal, Emma Wright, Gelare Ghajar-Rahimi, Daniel Epstein, Babak Orandi, Vineeta Kumar, Douglas Anderson, Morgan Greene, Markayla Bell, Stefani Yates, Kyle Moore, Jennifer Lafontaine, John Killian, Gavin Baker, Jackson Perry, Rhiannon Reed, Shawn Little, Alexander Rosenberg, James George, Jayme Locke
Rok vydání: 2023
Popis: 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. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages expressed genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft was detected. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.
Databáze: OpenAIRE