Chinese researchers have transplanted a lung from a genetically modified pig into a patient with confirmed brain death for the first time in the world. The organ remained viable and functional throughout the nine-day experiment, although complications were not avoided. The article was published in the journal Nature Medicine.
The idea of transplanting animal organs into humans (xenotransplantation) has been around for a long time, but genome editing systems, including CRISPR-Cas, have opened the way to its practical application. They can be used to remove the main antigens of an animal, insert human genes into the genome, and inactivate embedded viruses to improve tissue compatibility with the human body.
The first experiments in transplanting genetically modified pig kidneys and hearts were performed on brain-dead patients, and both organs have since been transplanted into fully living people in the United States. Chinese researchers reported the first transplant of a GM pig liver in addition to one in a brain-dead person with liver failure in May 2025 — the organ functioned for 10 days before being routinely removed. The lung is a more difficult organ to transplant because it is easily damaged and exposed to the surrounding air (which increases the risk of infection), and such experiments have not yet been conducted.
To prepare for the transplant, the Chinese company Clonorgan Biotechnology introduced six modifications into the genome of a Bama Xiang pig: they switched off the GGTA1, B4GALNT2 and CMAH genes responsible for the production of xenoantigens, and inserted the human genes CD55, CD46 and TBM, which regulate the complement system and modulate the immune response. Xin Xu from Guangzhou Medical University and colleagues took the left lung from a 22-month-old male GM pig weighing 70 kilograms and prepared it for transplantation.
The recipient was a 39-year-old man with confirmed brain death after hemorrhage, who could not become an organ donor due to contraindications. The operation was performed by median sternotomy, the cold ischemia time was 206 minutes. Immunosuppression with rabbit thymoglobulin, mycophenolate mofetil and tacrolimus was started the day before the operation, the last two drugs and methylprednisolone were administered daily thereafter. Postoperative immunosuppression and anti-inflammatory therapy also included basiliximab, rituximab, eculizumab, tofacitinib and belatacept.
The patient underwent continuous physiological, biochemical, and immunological monitoring, and graft biopsies were performed. After reperfusion, the transplanted lung was viable, expressed human transgenes, and was functional, with a fraction of oxygen uptake of 40 percent. Radiographs at 6 and 24 hours showed decreased lung transparency. CT one day after the procedure revealed a consolidation in the lower part of the lung, reminiscent of primary graft dysfunction (possibly due to reperfusion injury). Histology showed severe inflammatory edema with infiltration of CD68-positive cells and elevated levels of interleukin 6 and 10. B- and NK-cell levels fluctuated in the early postoperative period, while T-cell levels gradually increased from the third day.
On the third and sixth days after the intervention, immunoglobulin G deposits were observed in the xenograft along the alveolar septa; by the ninth day, they had significantly decreased. The level of immunoglobulin M was initially low, but increased by the ninth day, indicating secondary immune activation. Beginning on the third day, pronounced activation of the complement system was also observed. There were no signs of active infection, including that caused by porcine pathogens. The graft remained viable for 216 hours of the experiment, acute rejection did not occur, and hemodynamic parameters remained stable. After the planned period, the recipient was disconnected from life support systems.
The pilot experiment demonstrated the fundamental possibility of xenotransplantation of a genetically modified pig lung without acute rejection. However, despite the modifications, a pronounced immune response was observed, both cellular and humoral. This indicates the need to refine the immunosuppressive and anti-inflammatory therapy protocol, primarily by including blockade of the CD40 signaling pathway and suppression of interleukins and the complement system.
We wrote about xenotransplantation in detail in the article “About Pigs and People”.
