In a world-first, researchers in China successfully transplanted a genetically modified pig lung into a brain-dead human patient, where it functioned for nine days.
The milestone experiment, led by scientists at the First Affiliated Hospital of Guangzhou Medical University, sheds light on both the promise and obstacles of xenotransplantation.
Why Scientists Are Exploring Xenotransplantation
The shortage of suitable human donor organs remains a critical barrier for patients awaiting transplants. Xenotransplantation – using genetically modified pig organs – offers a potential bridge solution until human organs become available.
Researchers have previously tested pig kidneys and livers in human patients, with varying levels of success. Each organ, however, presents its own challenges due to differences in structure, function, and immune response.
Inside the Groundbreaking Procedure
The patient, a 39-year-old man declared brain-dead after a brain hemorrhage, received the pig lung with full family consent. Surgeons transplanted the left lung from a genetically engineered “six-gene-edited” Bama miniature pig. This donor pig was specifically modified using CRISPR to minimize immune rejection and inflammatory responses.
During surgery, the pig lung was carefully connected to the patient’s airways, arteries, and veins. Immunosuppressive drugs were administered and adjusted as researchers monitored the patient’s body for rejection signals.
Early Progress and Emerging Complications
In the critical hours after the transplant, the lung functioned without hyperacute rejection, a major initial concern in xenotransplantation. However, by 24 hours, swelling and fluid accumulation (pulmonary edema) were observed, likely caused by restored blood flow.
By days three and six, antibody-mediated rejection damaged the transplanted tissue further. This damage led to primary graft dysfunction, a severe lung injury seen in human transplants and the leading cause of lung transplant failure. Some recovery signs were detected by day nine, but researchers decided to terminate the experiment.
Why Lungs Pose Unique Challenges
Lungs present greater challenges than other organs in xenotransplantation because of their constant exposure to external air and pathogens. They must act as both a functional respiratory organ and a frontline immune defense system. This dual role makes them highly sensitive to immune rejection and inflammation.
Key Findings and Future Directions
The experiment demonstrated that pig lungs can be transplanted into humans without triggering immediate hyperacute rejection, an important step forward.
However, researchers emphasized the need to refine several areas, including genetic modifications, immunosuppressive regimens, and lung preservation techniques.
“The early onset of pulmonary edema underscores the importance of preventing primary graft dysfunction in future xenogeneic lung transplantation,” the research team noted.
They added that advancing this work requires better long-term strategies, including immune regulation and improved graft survival beyond the acute phase.
A Step Toward Expanding the Organ Supply
Over 100,000 patients worldwide await organ transplants every year, with donor shortages leaving many untreated. While pig organs are not yet a permanent solution, they may provide crucial temporary support for critically ill patients.
This experiment provides essential insights into immune, physiological, and genetic barriers that must be overcome. By building on these findings, future studies could bring xenotransplantation closer to clinical practice, offering new hope to patients in urgent need of transplants.