World-first pig lung transplant functions for nine days in human
Researchers have achieved a milestone in xenotransplantation by successfully transplanting a genetically modified pig lung into a brain-dead human recipient, where it remained viable and functional for nine days without hyperacute rejection or infection, according to research published in Nature Medicine.
Pig lungs
In a world-first achievement that could revolutionise organ transplantation, researchers have successfully demonstrated that a genetically modified pig lung can function in a human recipient for over nine days. The groundbreaking study, published in Nature Medicine on 25 August 2025, represents the first documented instance of cross-species lung transplantation and marks a pivotal development in addressing the critical global shortage of donor organs.
The historic procedure, led by Jianxing He and colleagues from Guangzhou Medical University, transplanted a lung from a six-gene-edited pig into a 39-year-old brain-dead male recipient. The lung xenograft maintained viability and functionality over the course of the 216 hours of monitoring without signs of hyperacute rejection or infection – a breakthrough that has eluded scientists for decades.
Sophisticated genetic engineering enables immune tolerance
The success hinged on sophisticated genetic modifications that transformed a standard pig organ into one compatible with human physiology. Using CRISPR gene-editing technology, the research team systematically removed three key xenoantigens – GGTA1, B4GALNT2, and CMAH – that typically trigger devastating immune responses in cross-species transplantation.
Simultaneously, they incorporated three human protective genes: CD55, CD46, and thrombomodulin (TBM), creating a biological bridge between species. This six-gene modification strategy represents years of careful genetic engineering designed to fool the human immune system into accepting the foreign organ.
Blood gas measurements from the transplanted lung demonstrated remarkable functional capacity, with partial pressure of oxygen reaching 100 mmHg at 40% fraction of inspired oxygen – performance levels approaching those of healthy human lungs.
Early complications reveal remaining challenges
Despite avoiding the feared hyperacute rejection that has historically doomed xenotransplantation attempts, the procedure encountered significant hurdles that light the way forward. Severe oedema resembling primary graft dysfunction emerged at 24 hours post-transplantation, likely due to ischaemia–reperfusion injury – a common complication even in human-to-human lung transplants.
More concerning were signs of antibody-mediated rejection appearing on days three and six. Immunological analysis revealed prominent deposits of immunoglobulin G along the alveolar septum, indicating the recipient’s immune system was mounting a coordinated attack against the foreign tissue. However, these deposits showed partial resolution by day nine, suggesting the immunosuppressive regimen was gaining control.
Intensive immunosuppression strategy proves partially effective
The medical team deployed an arsenal of immunosuppressive drugs to prevent rejection, including rabbit anti-thymocyte globulin, basiliximab, rituximab, eculizumab, tofacitinib, tacrolimus, mycophenolate mofetil, and tapering steroids. This comprehensive approach represented state-of-the-art immunosuppression, yet still could not completely prevent immune recognition of the xenograft.
The authors acknowledge that “improvements are needed to optimise both the genetic modifications made in the donor pig and the immunosuppressive drugs needed to avoid immune-mediated rejection of the lung and to maintain long-term function.”
Biosafety protocols address cross-species infection risks
A critical dimension of the research involved unprecedented pathogen surveillance to address infection risks inherent in xenotransplantation. The team conducted metagenomic and meta-transcriptomic analyses, detecting low levels of porcine lymphotropic herpesvirus-1 and PLHV-3 in the donor lung whilst confirming negative results for porcine endogenous retrovirus-C (PERV-C – a crucial safety milestone.
Infection markers procalcitonin and C-reactive protein in the recipient’s blood showed declining trends, suggesting no active cross-species pathogen transmission occurred during the monitoring period.
Transformative implications for global organ shortage crisis
This breakthrough comes at a critical juncture as organ shortage reaches crisis proportions worldwide. Current waiting lists for lung transplantation continue expanding, with many patients dying whilst awaiting suitable donors. Previous xenotransplantation successes with kidneys and hearts in brain-dead recipients had raised hopes, but lung transplantation remained the holy grail due to the organ’s unique physiological complexity.
The lung’s high blood flow, external air exposure, and dense concentration of endothelial antigens make it particularly susceptible to immune attack and ischaemia–reperfusion injury. Unlike kidneys or hearts, lungs cannot be easily supported by mechanical devices, making successful xenotransplantation even more challenging.
Future research pathways emerge from pioneering work
While acknowledging that “substantial challenges relating to organ rejection and infection remain,” the authors emphasise that their work provides crucial insights for future development. The study demonstrates that genetically modified pig lungs can maintain basic viability and function in humans – a fundamental prerequisite for eventual clinical translation.
The research team concludes that “further preclinical studies are necessary before clinical translation of this procedure,” but their work establishes a foundation for refined genetic modifications, enhanced immunosuppressive protocols, and improved preservation strategies.
Reference
He, J., Shi, J., Yang, C., et. al. (2025). Pig-to-human lung xenotransplantation into a brain-dead recipient. Nature Medicine. https://doi.org/10.1038/s41591-025-03861-x
