Med (New York, N.Y.) · 2026
First human decedent model of orthotopic multi-organ xenotransplantation: Whole liver and bilateral kidneys from a six-gene-edited pig.
СтатьяНазвание и аннотация: Перевод в очереди
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Liao Jixiang, An Sanqi, Dong Jianhui, Li ShihJung, Li Jianhui, Dong Lei, Luo Ziyang, Lan Liugen, Wen Ning, Wu Jihua, Wen Jiqiu, Lei Zhiying, Yang Dongge, Li Haibin, Li Minghu, Mo Yan, Chen Luying, Gao Zhao, Liu Xuyang, Qin Haisong, Wang Xiang, Chen Yajing, Yin Wenli, Huang Bihui, Li Wenxing, Oniscu Gabriel, Jiang Wenshi, Pan Dengke, Wang Zhengxin, Zhu Zhijun, Cai Jinzhen, Li Haitao, Gao Juntao, Kuang Xiaocong, Sun Xuyong
Аннотация
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).
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).