First human decedent model of orthotopic multi-organ xenotransplantation: Whole liver and bilateral kidneys from a six-gene-edited pig

Abstract

Background: We report orthotopic combined whole-liver and bilateral-kidney xenotransplantation (xeno-CLKT) from a six-gene-edited pig into a 53-year-old human decedent recipient.

Methods: After simultaneous implantation and reperfusion, graft function was monitored for nearly 5 days using continuous clinical assessments. Host responses were further characterized with single-cell RNA sequencing, proteomics, and metabolomics of blood and graft tissues collected before and after transplantation.

Findings: All grafts maintained basic physiological function throughout the observation period, with no evidence of hyperacute rejection. Early post-transplant immune analysis showed expansion of S100A12⁺ neutrophils, which emerged as central hubs in inferred intercellular communication networks. Systems-level metabolomic profiling indicated that post-transplant metabolic patterns remained positively correlated with the recipient's pre-transplant baseline, with generally higher magnitudes.

Conclusions: This study provides initial evidence for the feasibility of pig-to-human orthotopic whole-liver plus bilateral-kidney transplantation and identifies early immune and metabolic features that may inform perioperative management and future clinical translation.

Funding: The research was supported by the Guangxi Key Research and Development Program (AB24010059), the Shenzhen Medical Research Fund (SMAF) (B2302008), and the Guangdong Province Guangdong-Shenzhen Joint Key Project (2023B1515120083).

Keywords: deceased human; immune landscape; metabolomic profile; six-gene-edited pig; translation to humans; xenogeneic combined liver and kidney transplantation.