Cellular dynamics in pig-to-human kidney xenotransplantation.
Single-cell and longitudinal multi-omic profiling of pig-to-human kidney xenografts reveals time-resolved human immune infiltration and early signs of antibody-mediated rejection, even without hyperacute rejection.
Background
Genetically engineered porcine kidneys are being explored to address the shortage of human donor organs, but the physiological effects on the xenografts and the recipient immune response remain poorly characterized. Decedent (brain-dead) human models allow detailed study of the early cross-species immune interactions that will shape future clinical xenotransplantation.
Study design
Investigators performed single-cell RNA sequencing and longitudinal bulk RNA sequencing of porcine kidneys transplanted into human recipients, alongside longitudinal single-cell sequencing of recipient peripheral blood mononuclear cells. This multimodal approach traced the species origin of infiltrating cells and dissected xenograft-recipient interactions over time.
Key findings
Although no hyperacute rejection was detected, the analyses found endothelial cell and immune activation indicating early antibody-mediated rejection. Human immune cell infiltration appeared by roughly 12 hours and interferon-gamma-induced chemokine expression by about 48 hours post-transplantation, with corresponding two-phase recipient immune responses; a rapid increase in proliferative cells suggested activation of a porcine tissue-repair program.
Clinical implications
The time-resolved map of xenograft-recipient immune dynamics highlights specific cellular and molecular targets, including the humoral arm of rejection, that could guide gene-editing strategies and immunosuppression regimens. These insights are intended to optimize xenotransplantation outcomes as the field moves toward clinical trials.
Category
Transplant
Source
Med
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