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

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doi: 10.1038/s41591-025-03861-x.

Online forward of print.

Jianxing He^#^{1

2}, Jiang Shi^#^{3

4}, Chao Yang^#^{3

4}, Guilin Peng^#^{3

4}, Chunrong Ju^#⁴, Yi Zhao³, Hui Liu⁵, Ping He⁶, Xiaoqing Liu⁷, Zuopeng Zhang⁸, Chuanbao Chen⁴, Dengke Pan⁹, Zifeng Yang¹⁰, Wenda Guang¹⁰, Hongtao Li¹¹, Zhonghua Chen^{12

13}, Menyang Liu⁴, Hengrui Liang³, Weiqing Huang⁸, Kyeongman Jeon¹⁴, Toyofumi F Chen-Yoshikawa¹⁵, A Justin Rucker¹⁶, Amos Lal¹⁷, Nanshan Zhong^{18

19

20}, Kang Zhang^{21

22}, Xiaoyou Liu²³, Xin Xu^{24

25}

Affiliations

¹ Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Centre for Respiratory Disease, Guangzhou, China. [email protected].
² Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China. [email protected].
³ Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Centre for Respiratory Disease, Guangzhou, China.
⁴ Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
⁵ Department of Anesthesiology, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
⁶ Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
⁷ Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
⁸ Department of Emergency Medicine, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
⁹ Chengdu Clonorgan Biotechnology Co. Ltd, Chengdu, China.
¹⁰ State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
¹¹ Animal Experiment Center, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
¹² Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹³ Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.
¹⁴ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
¹⁵ Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁶ Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC, USA.
¹⁷ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁸ Department of Allergy and Clinical Immunology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou, China.
¹⁹ Guangzhou National Laboratory, Guangzhou, China.
²⁰ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou, China.
²¹ National Clinical Eye Research Center of Eye Hospital and Institute for Clinical Data Science, Wenzhou Medical University, Wenzhou, China.
²² Institute for AI in Medicine and Faculty of Medicine, Macau University of Science and Technology, Macau, China.
²³ Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China. [email protected].
²⁴ Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Centre for Respiratory Disease, Guangzhou, China. [email protected].
²⁵ Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China. [email protected].

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Jianxing He et al.

Nat Med.

2025.

doi: 10.1038/s41591-025-03861-x.

Online forward of print.

Authors

Affiliations

¹ Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Centre for Respiratory Disease, Guangzhou, China. [email protected].
² Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China. [email protected].
³ Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Centre for Respiratory Disease, Guangzhou, China.
⁴ Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
⁵ Department of Anesthesiology, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
⁶ Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
⁷ Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
⁸ Department of Emergency Medicine, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
⁹ Chengdu Clonorgan Biotechnology Co. Ltd, Chengdu, China.
¹⁰ State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
¹¹ Animal Experiment Center, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China.
¹² Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹³ Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.
¹⁴ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
¹⁵ Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁶ Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC, USA.
¹⁷ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁸ Department of Allergy and Clinical Immunology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou, China.
¹⁹ Guangzhou National Laboratory, Guangzhou, China.
²⁰ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou, China.
²¹ National Clinical Eye Research Center of Eye Hospital and Institute for Clinical Data Science, Wenzhou Medical University, Wenzhou, China.
²² Institute for AI in Medicine and Faculty of Medicine, Macau University of Science and Technology, Macau, China.
²³ Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China. [email protected].
²⁴ Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Centre for Respiratory Disease, Guangzhou, China. [email protected].
²⁵ Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Centre for Respiratory Disease, Guangzhou, China. [email protected].

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Abstract

Genetically engineered pig lungs haven’t beforehand been transplanted into people, leaving key questions unanswered concerning the human immune response within the context of a xenotransplanted lung and the opportunity of hyperacute rejection. Here, we report a case of pig-to-human lung xenotransplantation, by which a lung from a six-gene-edited pig was transplanted right into a 39-year-old brain-dead male human recipient following a mind hemorrhage. The lung xenograft maintained viability and performance over the course of the 216 hours of the monitoring interval, with out indicators of hyperacute rejection or an infection. Severe edema resembling main graft dysfunction was noticed at 24 hours after transplantation, probably attributable to ischemia-reperfusion damage. Antibody-mediated rejection appeared to contribute to xenograft injury on postoperative days 3 and 6, with partial restoration by day 9. Immunosuppression included rabbit anti-thymocyte globulin, basiliximab, rituximab, eculizumab, tofacitinib, tacrolimus, mycophenolate mofetil and tapering steroids, with changes made throughout the postoperative interval primarily based on assessments of immune standing. Although this examine demonstrates the feasibility of pig-to-human lung xenotransplantation, substantial challenges regarding organ rejection and an infection stay, and additional preclinical research are essential earlier than medical translation of this process.

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Conflict of curiosity assertion

Competing pursuits: D.P. is a co-founder of Chengdu Clonorgan Biotechnology Co. Ltd, Chengdu, China. The different authors declare competing pursuits.

References

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

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