<p>The shortage of donors is a major challenge for transplantation; however, organs from genetically modified pigs can serve as ideal supplements<sup><CitationRef CitationID="CR1">1</CitationRef>,<CitationRef CitationID="CR2">2</CitationRef></sup>. Until now, porcine hearts and kidneys have been successively transplanted into humans<sup><CitationRef AdditionalCitationIDS="CR4 CR5 CR6" CitationID="CR3">3</CitationRef>–<CitationRef CitationID="CR7">7</CitationRef></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.</p>

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Gene-modified pig-to-human liver xenotransplantation

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

摘要

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 humans37. 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.