Lung xenotransplantation: From the first human milestone to the path of clinical translation

Yubing Fang; Jiani Gao; Minjue Shan; Di Lu; Shusen Zheng; Chang Chen

doi:10.59717/j.xinn-med.2026.100264

The Innovation Medicine > 2026 Vol. 4 > No. 4 > 100264

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Lung xenotransplantation: From the first human milestone to the path of clinical translation

1.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200000, China
2.
Tongji University School of Medicine, Shanghai 200000, China
3.
Clinical Center for Thoracic Surgery Research, Tongji University, Shanghai 200000, China
4.
Department of Hepatobiliary and Pancreatic Surgery, NHC Key Laboratory of Combined Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
5.
Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou 310000, China
6.
General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310000, China
7.
These authors contributed equally

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Corresponding authors: zjuludi@zju.edu.cn (D.L.); zyzss@zju.edu.cn (S.Z.); chenthoracic@163.com (C.C.)
Received Date: March 25, 2026

Accepted Date: September 18, 2026

Published Online: September 20, 2026

The Innovation Medicine 4(4), https://doi.org/10.59717/j.xinn-med.2026.100264 | Cite this article

GRAPHICAL ABSTRACT

GRAPHICAL ABSTRACT

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Lung transplantation faces donor shortage; xenotransplantation using gene-edited pigs offers promise.
  
  In 2025, a gene-edited pig lung was transplanted into a brain-dead human, preventing hyperacute rejection.
  
  However, the nine-day observation showed severe primary graft dysfunction and antibody-mediated injury.
  
  This review analyzes lung xenograft barriers and a shift from passive camouflage to active immune remodeling.
  
  Clinical translation needs integrated solutions: donor production, biosafety, perfusion, and monitoring.

ABSTRACT

ABSTRACT

Lung transplantation remains the only curative treatment for end-stage lung diseases, yet a critical shortage of donor organs persists. Xenotransplantation using genetically modified pigs has emerged as a promising solution, with recent breakthroughs in cardiac and renal xenotransplantation demonstrating clinical feasibility. However, the unique anatomical and physiological characteristics of the lung pose distinct challenges that have delayed progress in pulmonary xenotransplantation. The first reported transplantation of a gene-edited pig lung into a brain-dead human recipient in 2025 represents a pivotal milestone, successfully preventing hyperacute rejection through triple-gene knockout combined with transgenic expression of human complement regulatory proteins and thrombomodulin. Yet the nine-day observation window revealed persistent challenges, including severe primary graft dysfunction and active antibody-mediated injury, highlighting that current genetic modifications remain inadequate for achieving long-term graft survival. This review systematically analyzes the layered immunological and physiological barriers to lung xenotransplantation and evaluates evolving intervention strategies that reflect a paradigm shift from passive molecular camouflage toward active immunological remodeling. Looking beyond biological barriers, successful clinical translation requires integrated solutions spanning scalable donor production systems, surgical adaptation, rigorous biosafety frameworks, ex vivo perfusion platforms, and non-invasive monitoring technologies. Ultimately, the success of lung xenotransplantation will depend not on isolated technological breakthroughs but on the systematic integration of genetic engineering, immune modulation, and translational infrastructure, offering new hope to patients with end-stage lung disease.

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Fang Y., Gao J., Shan M., et al. (2026). Lung xenotransplantation: From the first human milestone to the path of clinical translation. The Innovation Medicine 4:100264. https://doi.org/10.59717/j.xinn-med.2026.100264

Fang Y., Gao J., Shan M., et al. (2026). Lung xenotransplantation: From the first human milestone to the path of clinical translation. The Innovation Medicine 4:100264. https://doi.org/10.59717/j.xinn-med.2026.100264

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