A team of Chinese researchers has performed a pig-to-human lung transplant for the first time.

A team of Chinese researchers from Guangzhou University has achieved a new milestone in cross-species transplant research by transplanting a genetically modified pig lung into a brain-dead human for the first time . The organ remained viable and functional for nine days, according to the results of the study, published Monday in the journal Nature Medicine.

The discovery opens another small door to the possibility that, in the future, the shortage of human organs for transplantation could be resolved with xenotransplantation , which consists of transplanting from one species to another. Previous studies have already demonstrated the feasibility of doing this with kidneys, hearts, and livers from genetically modified pigs to humans. In fact, last March, the journal 'Nature' published the findings of another group of Chinese researchers who performed the first genetically modified pig liver transplant in 2024 on a 50-year-old brain-dead person. After 10 days, they evaluated the condition of the organ and the recipient and verified its proper functioning.

In the US, there have also been recent reports of pig-to-human kidney transplants, such as that of Towana Looney , the oldest recipient of a functioning pig organ transplant. She was the third person in the world to receive a kidney transplant from a genetically modified pig, and it functioned well for more than four months, outperforming previous cases, although it ultimately had to be removed due to acute rejection. And in 2022, also in the US , a pig's heart beat for the first time inside a human body for two months. David Bennett, 57, who was given up for dead due to serious heart conditions, received the organ from a genetically modified animal in a historic transplant.

However, lung transplantation presents different challenges than transplantation of other solid organs, due to its anatomical and physiological complexity.

"The significance of this breakthrough lies in the fact that, until now, xenotransplant experiments in humans had been limited to kidneys, hearts, and livers, but never to lungs. This organ poses an even greater challenge due to its delicate physiological balance: it receives extremely high blood flow and is continuously exposed to ambient air, making it particularly vulnerable," says Beatriz Domínguez-Gil, current director of the National Transplant Organization (ONT). Speaking to SMC Spain, the expert believes this study is particularly relevant because "it constitutes proof of concept that, with further improvements, lung xenotransplantation could in the future become a real option for saving lives" because "the clinical need is enormous."

There are many respiratory diseases that may be candidates for a transplant, but " around 80% of the indications are for COPD , also known as emphysema, and pulmonary fibrosis . The other 20% are for other types of more rare respiratory diseases, many of them orphan, without specific treatment, because they are low in prevalence," says, in statements to ABC, Dr. Víctor Mora, pulmonologist at the Marqués de Valdecilla University Hospital, medical coordinator of the Lung Transplant Program and member of the Interventional Pulmonology, Lung Function and Transplant Area of ​​SEPAR.

According to the Global Observatory on Donation and Transplantation (GODT), coordinated by the National Transplant Organization (NTO) as a collaborating center of the World Health Organization (WHO), 8,236 lung transplants were performed worldwide in 2024, representing a 6% increase compared to the previous year. However, the NTO director warns, demand far exceeds organ availability . In the European Union alone, 2,221 patients received a lung transplant in 2024, compared to the 3,926 who remained on the waiting list throughout that year; of these, 216 died before accessing the transplant. In Spain, the world leader in this practice, 623 transplants were performed in 2024, representing a rate of 13.1 per million population, the highest rate in the world.

Patients who require transplants are those in very advanced stages of the disease. And although Spain has been a world leader for 30 years in the number of donors per million population, there is an organ shortage. "We have an imbalance between the number of patients with respiratory diseases who could be candidates for a transplant and the number of donors we have, which forces us to be very selective with the recipient candidates on the waiting list. We include those with the greatest likelihood of success," explains Dr. Mora.

In this study, Dr. Jianxing He and his colleagues transplanted the left lung of a genetically modified pig into a 39-year-old man declared brain dead after four clinical evaluations, while retaining the deceased patient's remaining lung. They monitored the function of the transplanted lung and the response of the human immune system.

The pig from which the lung was obtained had undergone six genetic modifications using CRISPR to make it more compatible with humans by removing antigens that could activate the recipient's defense system after the transplant. The authors observed that the lung was not immediately rejected by the immune system and remained viable and functional for 9 days. However, they detected signs of lung damage 24 hours after the transplant and signs of antibody-mediated lung rejection 3 and 6 days later, so the experiment was terminated on day nine.

The authors believe these findings represent a first step toward pig-to-human lung transplantation . However, they acknowledge that improvements are needed to optimize both the genetic modifications made to the donor pig and the immunosuppressive drugs needed to prevent immune-mediated lung rejection and maintain long-term lung function.

Lung transplantation is the most difficult of all organs. "One of the problems is that it's technically more complex because many anatomical aspects and technical issues come into play during the surgery. But it's also difficult on an immunological and infectious level, the two main problems after any type of transplant. It's one of the organs that requires the highest level of immunosuppression because it has a higher rejection rate, which forces us to be very aggressive and significantly lower our defenses, and this greatly increases the risk of infection in an organ that's the only one open to the outside world. The kidney, liver, and heart are sterile organs, but the lung, with each breath, is in contact with the environment, and the number of infections is more frequent," explains Dr. Mora.

"Within the race between North American and Chinese researchers to position themselves in the promising world of xenotransplantation, and following experiences in living humans and/or brain-dead patients with kidneys, hearts, and livers, the group from the University of Guangzhou (China) has tackled what is probably the most delicate and complex organ when it comes to achieving a functioning transplant: the lung ," says Rafael Matesanz, creator and founder of the National Transplant Organization (ONT). In statements to SMC, the former director of the ONT points out as "positive data" the fact that there was no hyperacute rejection or infection derived from the graft, which apparently maintained reasonable functionality during the study period. "However, edema was recorded in the first few days, probably due to ischemia-reperfusion, and signs of rejection in the following days. Given the time limitation of the brain-death situation, it is not possible to assess its evolution. Apart from the fact that, by preserving the native lung with good function, the assessment of the functional evolution of the graft is complicated," he clarifies.

Aside from demonstrating that this type of intervention can be performed, for Matesanz, " there are more unknowns than answers derived from this study. It is evident that further research will be necessary, but the possibility of achieving good outcomes in one of these lungs in a patient, with acceptable survival, seems remote and, of course, much more complicated than in the case of a kidney or liver."