Gene-modified pig-to-human liver xenotransplantation

The shortage of donors is a major challenge for transplantation; however, organs from genetically modified pigs can serve as ideal supplements<sup>1,2</sup>. Until now, porcine hearts and kidneys have been successively transplanted into humans<sup>3-7</sup>. 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 10 days. Two hours after portal vein reperfusion of the xenograft, goldish bile was produced, increasing to 66.5 ml 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 3 days 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.

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Publication Details

Journal
Nature
Published
2025-03-26
DOI
https://doi.org/10.1038/s41586-025-08799-1
Citations
76
Primary Topic
Xenotransplantation and immune response
Type
article
Field-Weighted Citation Impact
152.49
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article

Gene-modified pig-to-human liver xenotransplantation

Dengke Pan, Hailong Dong, Zhibin Lin, Dan Wei et al.
76 citations
Nature
Xenotransplantation and immune response
152.49
article

Gene-modified pig-to-human liver xenotransplantation

Dengke Pan, Hailong Dong, Zhibin Lin, Dan Wei, Kefeng Dou, Zhengcai Liu, Shuqiang Yue, Xijing Zhang, Haojie Xu, Kaishan Tao, Min Li, Zhe Wang, Weixun Duan, Haimin Li, Zhao-Xu Yang, Jiayun Liu, Yanling Yang, Rui Ding, Jipeng Li, Xuan Zhang, Lin Wang, Hong Zhang, Jingwen Wang, Wen‐Jin Yin, Desheng Wang, Ming Yu, Lin Li, Shiren Sun, Wenjie Song, Minwen Zheng, Hongtao Zhang, Yong Chen, Donglong Bian, Weijun Qin, Juanli Duan
article en
76 citations

Abstract

The shortage of donors is a major challenge for transplantation; however, organs from genetically modified pigs can serve as ideal supplements<sup>1,2</sup>. Until now, porcine hearts and kidneys have been successively transplanted into humans<sup>3-7</sup>. 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 10 days. Two hours after portal vein reperfusion of the xenograft, goldish bile was produced, increasing to 66.5 ml 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 3 days 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.

NatureVol. 641(8064)
Xijing Hospital (CN), Air Force Medical University (CN)
Openalex Percentile: Top 0%
Xenotransplantation and immune response
152.49
DOIOpen Access PDFOpenAlex
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