[News] World-First Gene-Edited Pig Lung Transplant in China Marks Breakthrough in Xenotransplantation

August 27, 2025 – In a groundbreaking achievement, Chinese scientists from the First Affiliated Hospital of Guangzhou Medical University, led by Professors Xu Xin, Liu Xiaoyou, and He Jianxing, have successfully performed the world’s first gene-edited pig-to-human lung transplant.

Published on August 25, 2025, in Nature Medicine, the study details the transplantation of a genetically modified pig lung into a brain-dead human recipient, with the organ functioning for 216 hours (9 days) without succumbing to hype acute rejection. This milestone, following China’s earlier successes in pig liver and kidney xenotransplants, positions the country at the forefront of addressing the global organ shortage crisis through xenotransplantation.

Overcoming the "Hardest Nut to Crack"

Organ transplantation has saved countless lives, but the severe global shortage of donor organs leaves thousands of patients waiting, many of whom pass away before receiving a transplant.

Xenotransplantation—transplanting organs from one species to another, particularly from gene-edited pigs to humans—has emerged as a promising solution. While pig-to-human kidney and heart transplants have seen significant progress, lung xenotransplantation has remained the most challenging due to the lung’s complex physiology and robust immune responses.

The study, titled “Pig-to-human lung xenotransplantation into a brain-dead recipient,” reports the successful transplantation of a left lung from a pig with six genetic modifications into a 39-year-old male brain-dead recipient. The procedure, conducted with informed consent from the patient’s family and ethical oversight, marks a historic first in cross-species lung transplantation.

Precision Genetic Engineering

The donor pig, a Bama miniature pig provided by Chengdu Zhongke Aoge Biotechnology Co., Ltd., underwent six critical genetic edits to minimize immune rejection:

• Three Gene Knockouts (KO): The genes GGTA1, B4GALNT2, and CMAH, responsible for producing pig cell surface antigens (α-Gal, SDA, Neu5Gc) that trigger hype acute rejection, were removed.

• Three Human Gene Knock-Ins (KI): Human genes CD46, CD55 (complement regulatory proteins), and TBM (thrombomodulin, to prevent blood clotting) were inserted, effectively “cloaking” the pig lung to evade human immune attacks.

  
  

These modifications, achieved through CRISPR-mediated HDR repair, allowed the pig lung to avoid hype acute rejection—a rapid, deadly immune response typically occurring within minutes to hours of transplantation. Post-surgery, the lung exhibited healthy blood flow, a red appearance, and effective gas exchange, demonstrating the success of the genetic and immunosuppressive strategies.

Challenges and Insights

Despite this success, the study revealed significant challenges:

• Primary Graft Dysfunction (PGD): Within 24 hours post-transplant, chest X-rays and CT scans showed severe lung edema and consolidation, indicative of PGD, likely due to ischemia-reperfusion injury. Pathology confirmed macrophage infiltration and tissue swelling.

• Antibody-Mediated Rejection (AMR): By days 3 and 6, biopsies revealed human IgG and complement C4d deposits on alveolar walls, signaling AMR. Serum tests confirmed rising anti-pig IgG levels, indicating immune activation despite a robust immunosuppressive regimen including ant thymocyte globulin, basiliximab, rituximab, eculizumab, tofacitinib, tacrolimus, mycophenolate mofetil, and tapering glucocorticoids.

• Partial Recovery and Late IgM Response: By day 9, IgG deposits decreased, and lung function (compliance and gas exchange) improved. However, a new IgM immune response emerged, suggesting a delayed immune challenge.

The experiment was terminated on day 9 at the family’s request, but the lung maintained vitality and function throughout, with no evidence of pathogen transmission, including pig endogenous retroviruses (PERV), confirmed through metagenomic and met transcriptomic analyses.

Global Context and China’s Leadership

This breakthrough builds on China’s prior achievements in xenotransplantation. In March 2025, a team led by Academician Dou Kefeng at Xijing Hospital, Air Force Medical University, performed the world’s first pig-to-human liver transplant, with the organ functioning for 10 days. Earlier, in March 2025, the same hospital conducted a pig kidney transplant in a living patient with end-stage renal disease, who remains alive and stable 173 days post-surgery—one of only two such patients worldwide.

Globally, xenotransplantation has gained momentum. In 2021, NYU Langone Health performed the first pig-to-human kidney transplant in a brain-dead recipient, followed by the University of Maryland’s pig heart transplant in a living patient in 2022. However, lung xenotransplantation’s unique challenges—intense immune responses, sensitivity to ischemia-reperfusion injury, and infection risks due to environmental exposure—make China’s achievement a standout.

Professor Pan Dengke, founder of Chengdu Zhongke Aoge and a key contributor to the donor pigs, emphasized the complexity of lung xenotransplantation: “The lung’s extensive capillary network and resident macrophage population heighten rejection risks. Our results, while expected within known biological constraints, provide critical mechanistic insights.”

Implications and Future Directions

The study, lauded by experts like Justin Chan of NYU Langone and Beatriz Domínguez-Gil of Spain’s National Transplant Organization, lays a foundation for future research. It highlights the need for further genetic modifications, such as adding human genes like EPCR, vWF, or CD47 to mitigate clotting and inflammation, and optimizing immunosuppressive protocols to control PGD and AMR.

While clinical application remains distant, this research underscores the feasibility of pig-to-human lung transplantation and provides a roadmap for addressing its challenges. With global organ demand far outstripping supply—only 10% of transplant needs met annually, per WHO, and a 1:30 donor-to-patient ratio in China—xenotransplantation offers hope for millions with end-stage organ failure.

Professor He Jianxing, the study’s lead, told Xinhua: “This milestone paves the way for further innovation in xenotransplantation, bringing us closer to clinical translation.” As China continues to lead with pioneering pig liver, kidney, and now lung transplants, the global medical community watches closely, hopeful for a future where organ shortages are a thing of the past.

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