第四军医大学窦科峰研究团队报道了基因修饰猪到人的肝脏异种移植。这一研究成果于2025年3月26日发表在国际顶尖学术期刊《自然》上。

供体短缺是移植面临的主要挑战；然而，来自转基因猪的器官可以作为理想的补充物。到目前为止，猪的心脏和肾脏已经被陆续移植到人类身上。在这项研究中，异位辅助移植的主题是将六基因编辑的猪肝捐赠给脑死亡受体。在随后的10天内监测移植物功能、血流动力学以及受体的免疫和炎症反应。异种移植门静脉再灌注2小时后产生黄胆汁，术后第10天升高至66.5。手术后猪肝源性白蛋白也增加。丙氨酸转氨酶水平维持在正常范围内，而天冬氨酸转氨酶水平在术后第1天升高，然后迅速下降。猪肝动脉、门静脉和肝静脉血流速度保持在可接受水平。虽然术后早期血小板数量下降，但最终恢复到正常水平。组织学分析表明，猪肝再生能力强，无排斥反应。抗胸腺细胞球蛋白抑制T细胞活性，手术后几天B细胞活性增加3，然后用利妥昔单抗抑制。围手术期免疫球蛋白G和免疫球蛋白M水平无明显变化。C反应蛋白和降钙素原水平最初升高，然后迅速下降。直到研究完成，异种移植物仍保持功能。

附：英文原文

Title: Gene-modified pig-to-human liver xenotransplantation

Author: Tao, Kai-Shan, Yang, Zhao-Xu, Zhang, Xuan, Zhang, Hong-Tao, Yue, Shu-Qiang, Yang, Yan-Ling, Song, Wen-Jie, Wang, De-Sheng, Liu, Zheng-Cai, Li, Hai-Min, Chen, Yong, Ding, Rui, Sun, Shi-Ren, Yu, Ming, Li, Ji-Peng, Duan, Wei-Xun, Wang, Zhe, Wang, Jing-Wen, Liu, Jia-Yun, Zheng, Min-Wen, Zhang, Xi-Jing, Yin, Wen, Qin, Wei-Jun, Bian, Dong-Mei, Li, Lin, Li, Min, Lin, Zhi-Bin, Xu, Hao, Wei, Dan, Zhang, Hong, Duan, Juan-Li, Pan, Deng-Ke, Dong, Hai-Long, Wang, Lin, Dou, Ke-Feng

Issue&Volume: 2025-03-26

Abstract: The shortage of donors is a major challenge for transplantation; however, organs from genetically modified pigs can serve as ideal supplements1,2. Until now, porcine hearts and kidneys have been successively transplanted into humans3,4,5,6,7. In this study, heterotopic auxiliary transplantation was used to donate a six-gene-edited pig liver to a brain-dead recipient. The graft function, haemodynamics, and immune and inflammatory responses of the recipient were monitored over the subsequent 10days. Two hours after portal vein reperfusion of the xenograft, goldish bile was produced, increasing to 66.5ml by postoperative day 10. Porcine liver-derived albumin also increased after surgery. Alanine aminotransferase levels remained in the normal range, while aspartate aminotransferase levels increased on postoperative day 1 and then rapidly declined. Blood flow velocity in the porcine hepatic artery and portal and hepatic veins remained at an acceptable level. Although platelet numbers decreased early after surgery, they ultimately returned to normal levels. Histological analyses showed that the porcine liver regenerated capably with no signs of rejection. T cell activity was inhibited by anti-thymocyte globulin administration, and B cell activation increased 3days after surgery and was then inhibited by rituximab. There were no significant peri-operative changes in immunoglobulin G or immunoglobulin M levels. C-reactive protein and procalcitonin levels were initially elevated and then quickly declined. The xenograft remained functional until study completion.

DOI: 10.1038/s41586-025-08799-1

Source: https://www.nature.com/articles/s41586-025-08799-1