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

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. 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.

Acceptance of xenotransplantation by patients waiting for organ donation: A qualitative study

“…Although immune responses to animal‐to‐human transplants are uncertain, xenotransplantation is rapidly approaching the clinical arena 25 . Although technology and science advances, what will be done will be as much as people accept.…”

“…Although immune responses to animal-to-human transplants are uncertain, xenotransplantation is rapidly approaching the clinical arena. 25 Although technology and science advances, what will be done will be as much as people accept. In this study, the majority of the participants had a positive opinion about the acceptance of xenotransplantation and were encouraged by the idea that transplantation from animals might be possible in the future.…”