Abstract
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.
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Data availability
These data are not publicly accessible due to ethical and institutional restrictions safeguarding research subject privacy. De-identified recipient data supporting the findings of this study are available upon request from the corresponding author, subject to ethics and institutional approval. Requests will be reviewed within 2 weeks.
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Acknowledgements
We thank the family of the decedent for their invaluable contribution to the advancement of lung xenotransplantation and scientific research. We also thank the clinical and laboratory teams at the First Affiliated Hospital of Guangzhou Medical University and the National Clinical Centre for Respiratory Disease, including the lung xenotransplantation clinical team (Y. Zeng, J. Mao, L. Wang, W. Shen, J. Zhang, T. Xing, Y. Xue, J. Fan, Y. Ouyang and X. Zhang), the nursing team (Y. Chen, D. Huang, R. Li, X. Li, M. Kuang and X. Li), anesthesiologist Y. Zhou, laboratory staff (W. Wang, L. Liu, Z. Huang and M. Yu) and the organ procurement organization personnel (L. Wang, L. Wang, Y. Wang and K. Li) for their unwavering support. We acknowledge L. Burdorf and C. Laird’s team for their pioneering work on NHP lung xenotransplantation, which inspired this research, particularly in the experimental design.
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J.H., J.S., C.Y., G.P., C.J., H.L., P.H., X.L., Z.Z., C.C., D.P., Z.Y., W.G., H.T.L., Z.C., M.L., H.R.L., Y.Z., W.H., K.J., T.F.C.-Y., A.J.R., A.L., X.L. and X.X. contributed to the conception and design of the study. J.S., C.Y., G.P., C.J., H.L., P.H., X.L., Z.Z., C.C., D.P., Z.Y., W.G., H.T.L., Z.C., M.L., H.R.L., Y.Z. and W.H. performed the data collection and analysis. J.H., X.L. and X.X. supervised the project. J.H., J.S., C.Y., G.P., X.L. and X.X. drafted the manuscript, with critical revisions from J.H., K.Z., J.S., X.L., Y.Z., N.Z. and X.X. All authors reviewed and approved the final manuscript.
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D.P. is a co-founder of Chengdu Clonorgan Biotechnology Co. Ltd, Chengdu, China. The other authors declare competing interests.
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Nature Medicine thanks Hidetaka Hara and Eckhard Wolf for their contribution to the peer review of this work. Primary Handling Editor: Michael Basson, in collaboration with the Nature Medicine team.
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He, J., Shi, J., Yang, C. et al. Pig-to-human lung xenotransplantation into a brain-dead recipient. Nat Med (2025). https://doi.org/10.1038/s41591-025-03861-x
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DOI: https://doi.org/10.1038/s41591-025-03861-x
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