Collaborators from NYU Langone Health and Revivicor, funded by NIH and others, published these findings in Nature on November 13, 2025, signaling progress toward trials.

Researchers transplanted a gene-edited pig kidney into a brain-dead human recipient with a beating heart to monitor immune responses over 61 days, enabling detailed tissue, blood, and fluid analysis not feasible in living patients or primates.

New NYU Langone Health study reveals immune mechanisms behind pig-to-human kidney rejection and demonstrates how to reverse rejection in a brain-dead donor model, informing future clinical trials.

The work shows a sequence of immune events, with early humoral and innate responses and later T-cell–driven rejection, guiding targeted immunomodulation strategies.

Rejection was reversed using FDA-approved drugs that tempered both antibody and T-cell responses, with no lasting kidney damage after intervention.

Early-warning biomarkers were identified that could predict rejection up to five days before clinical signs, enabling proactive management.

Two Nature papers delineate immune waves: innate response around day 21, macrophage-driven activity around day 33, and T-cell–driven rejection around day 45, with biomarkers offering early warning signals.

Multi-omics integration highlighted potential therapeutic targets and pathways, including SPP1/Osteopontin and CXCL9+ macrophages, to guide immunomodulation and biomarker discovery.

Clinical translation hinges on validating findings across more decedents and live patients, with ongoing exploration of targeted therapies based on identified antibodies and T cells.

Early humoral and innate responses dominate the first weeks, with plasmablasts, NK cells, and dendritic cells rising between days 10 and 28, followed by clonal expansion of IgG/IgA-producing B cells leading to antibody-mediated rejection by day 33.

Complement activation involving both human and pig components was observed, and blocking post-abMR complement helped attenuate human complement activity, suggesting a therapeutic leverage to extend graft survival.

Multi-omics analysis tracked about 5,100 expressed genes and immune cell types day by day, providing granular snapshots of rejection and systemic biomarkers.