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<p>Genetically engineered pig lungs have not previously been transplanted into humans, leaving key questions unanswered regarding the human immune response in the context of a xenotransplanted lung and the possibility of hyperacute rejection. Here, we report a case of pig-to-human lung xenotransplantation, in which a lung from a six-gene-edited pig was transplanted into a 39-year-old brain-dead male human recipient following a brain hemorrhage. The lung xenograft maintained viability and functionality over the course of the 216 hours of the monitoring period, without signs of hyperacute rejection or infection. Severe edema resembling primary graft dysfunction was observed at 24 hours after transplantation, potentially due to ischemia–reperfusion injury. Antibody-mediated rejection appeared to contribute to xenograft damage on postoperative days 3 and 6, with partial recovery by day 9. Immunosuppression included rabbit anti-thymocyte globulin, basiliximab, rituximab, eculizumab, tofacitinib, tacrolimus, mycophenolate mofetil and tapering steroids, with adjustments made during the postoperative period based on assessments of immune status. Although this study demonstrates the feasibility of pig-to-human lung xenotransplantation, substantial challenges relating to organ rejection and infection remain, and further preclinical studies are necessary before clinical translation of this procedure.</p>

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Pig-to-human lung xenotransplantation into a brain-dead recipient

  • 期刊论文

  • 发表日期：

    2025年8月25日

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  • Jianxing He,
  • Jiang Shi,
  • Chao Yang,
  • Guilin Peng,
  • Chunrong Ju,
  • Yi Zhao,
  • Hui Liu,
  • Ping He,
  • Xiaoqing Liu,
  • Zuopeng Zhang,
  • Chuanbao Chen,
  • Dengke Pan,
  • Zifeng Yang,
  • Wenda Guang,
  • Hongtao Li,
  • Zhonghua Chen,
  • Menyang Liu,
  • Hengrui Liang,
  • Weiqing Huang,
  • Kyeongman Jeon,
  • Toyofumi F. Chen-Yoshikawa,
  • A. Justin Rucker,
  • Amos Lal,
  • Nanshan Zhong,
  • Kang Zhang,
  • Xiaoyou Liu,
  • Xin Xu

摘要

Genetically engineered pig lungs have not previously been transplanted into humans, leaving key questions unanswered regarding the human immune response in the context of a xenotransplanted lung and the possibility of hyperacute rejection. Here, we report a case of pig-to-human lung xenotransplantation, in which a lung from a six-gene-edited pig was transplanted into a 39-year-old brain-dead male human recipient following a brain hemorrhage. The lung xenograft maintained viability and functionality over the course of the 216 hours of the monitoring period, without signs of hyperacute rejection or infection. Severe edema resembling primary graft dysfunction was observed at 24 hours after transplantation, potentially due to ischemia–reperfusion injury. Antibody-mediated rejection appeared to contribute to xenograft damage on postoperative days 3 and 6, with partial recovery by day 9. Immunosuppression included rabbit anti-thymocyte globulin, basiliximab, rituximab, eculizumab, tofacitinib, tacrolimus, mycophenolate mofetil and tapering steroids, with adjustments made during the postoperative period based on assessments of immune status. Although this study demonstrates the feasibility of pig-to-human lung xenotransplantation, substantial challenges relating to organ rejection and infection remain, and further preclinical studies are necessary before clinical translation of this procedure.