For the first time, surgeons have transplanted a genetically modified pig lung into a brain-dead human, where it functioned for nine days. The study, reported in Nature Medicine, represents a significant milestone in xenotransplantation, a field aimed at addressing the global shortage of donor organs. The World Health Organization estimates that only around 10% of the demand for organ transplants is currently met.
The left lung from a Chinese Bama Xiang pig, genetically modified with six changes to reduce rejection, was transplanted into a 39-year-old brain-dead male. Researchers observed that the lung remained viable over 216 hours, avoided hyperacute rejection, and showed no signs of infection. However, fluid buildup and progressive antibody-mediated damage occurred despite strong immunosuppressive therapy. Experts noted that the recipient’s remaining natural lung likely masked some of the damage.
Challenges of Lung Xenotransplantation
Unlike kidneys or hearts, lungs are particularly challenging for xenotransplantation because they constantly interact with the external environment. This exposes them to pathogens, pollutants, and other stressors, making them highly sensitive to immune reactions. Andrew Fisher of Newcastle University emphasized that while the study is a valuable step forward, it represents only incremental progress, and lung xenotransplantation is not yet ready for patients.
Peter Friend from Oxford added that brain death itself creates inflammation, complicating assessment of the transplant’s function. Researchers stressed the need for further refinement, including optimizing immunosuppressive protocols, improving genetic modifications, enhancing organ preservation, and evaluating long-term graft performance.
Future Directions
Beyond pig-to-human transplants, other strategies are being explored to increase organ availability. These include reconditioning marginal human donor lungs, growing humanized organs in pigs or sheep, and using stem cells to remodel donor organs. Experts note that some of these methods, particularly reconditioning human lungs, could provide solutions in a shorter timeframe and have a significant impact on transplant outcomes.
While xenotransplantation of lungs holds promise, researchers caution that much work remains before pig lungs can be safely used in living patients.
