Nature biomedical engineering · 2026
Orthotopic liver xenotransplantation from gene-modified pig to decedent human.
СтатьяНазвание и аннотация: Перевод в очереди
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Tao Kaishan, Yang Zhaoxu, Zhang Xuan, Zhang Hongtao, Lin Zhibin, Yue Shuqiang, Yang Yanling, Song Wenjie, Wang Desheng, Liu Zhengcai, Li Haimin, Chen Yong, Zhou Jingshi, Ding Rui, Sun Shiren, Yu Ming, Li Jipeng, Duan Weixun, Wang Zhe, Wang Jingwen, Liu Jiayun, Zheng Minwen, Zhang Xijing, Yin Wen, Qin Weijun, Bian Dongmei, Li Lin, Li Min, Xu Hao, Wei Dan, Zhang Hong, Zhang Li, Wang Quancheng, Duan Juanli, Lu Zhihong, Dong Hailong, Pan Dengke, Wang Lin, Dou Kefeng
Аннотация
Xenotransplantation offers a critical solution to global organ shortages. Recent reports show that genetically engineered porcine livers can provide auxiliary metabolic support in human recipients and non-human primates. However, orthotopic pig-to-human liver xenotransplantation remained a challenge owing to the liver immunological and physiological complexity. Here we report the orthotopic pig-to-human liver xenotransplantation in a brain-deceased individual. Throughout the 11-day observation period, the xenograft maintains continuous albumin and bile production with normal composition, albeit at a relatively low level. Systemic haemodynamic stability is maintained, although suboptimal hepatic perfusion resulting from microthrombosis occurred, which likely contributed substantially to late-phase hepatic functional decline. Coagulation abnormalities manifest as progressive thrombocytopenia and reduced clotting factor activity. Histopathological analysis reveals scant T/B cell infiltration and immunoglobulin G deposition, yet demonstrates prominent innate immune activation and immunoglobulin M-mediated complement activation. While certain positive indicators emerge, critical challenges including endothelial damage, microthrombosis and coagulopathy remain. This study highlights the importance of genetic engineering and targeted immunosuppressive approaches to advance the clinical translation of xenogeneic liver transplantation.