NEW YORK, NY (Nov. 13, 2025)--A study of a pig kidney that flourished for two months in a brain-dead recipient shows that a protocol developed by Columbia University immunologists can help prevent long-term rejection of a xenotransplant.
In the study, surgeons at New York University Langone Health transplanted a pig kidney and the same animal's thymus gland into a 57-year-old man with glioblastoma who had been declared brain-dead at the hospital. The study was published in Nature.
Studying xenotransplants (organs from other species) in brain-dead individuals gives researchers more extensive details about how a transplanted organ is working and how the recipient's immune system is reacting than is possible with living patients. But until now, xenotransplant studies in decedents have been short, ending one or two weeks after the surgery.
"In our study, we obtained an unprecedented number of tissue, blood, and fluid samples from the recipient, allowing us to monitor immunological changes over time and identify ways to improve the success of xenotransplantation," says Megan Sykes, director of the Columbia Center for Translational Immunology, one of the study's co-leaders who developed the thymus-kidney strategy.
Pig thymus reduces rejection
Over the past three decades, Sykes and her colleagues have studied how to train a transplant recipient's immune system to tolerate a donated organ, including xenotransplants.
In animal studies, Sykes and her team have found that transplanting tissue from a donor's thymus—which teaches immune cells to distinguish between native and foreign tissue—along with the replacement organ reduces the immune attack on the donated organ, producing remarkable long-term results.
The approach also seemed to work in the decedent.
"Our analyses suggested that the transplanted pig thymus may have helped to restrain the recipient's immune system from attacking the kidney."
The thymus also may have prevented a dangerous loss of proteins from the body, which has hampered xenotransplants in living patients. "One of the kidney's jobs is to keep proteins in the body and prevent their release into urine," Sykes says. "With the thymo-kidney transplant, we saw no evidence of this complication."
Attack by recipient's immune system still a challenge
Despite the calming presence of the pig thymus, Sykes's analyses found immunological challenges that still need to be addressed to improve long-term outcomes with xenotransplants.
One month after transplantation, a rejection episode that was thought to be caused by antibodies occurred. However, studies in the Sykes lab implicated the recipient's own T cells that existed before the transplant in attacking the pig kidney. The rejection episode was successfully treated by temporarily eliminating the recipient's T cells.
The researchers also found new antibodies directed against the donor organ after the transplant, but not against the pig antigens predicted to pose a problem (and which have been edited by some xenotransplant developers).
"These antibodies are directed at other unknown pig antigens, and I think it will be really important to identify them to improve future xenotransplants," Sykes says.
Minimal gene editing required
The pig kidney transplanted in this study had been genetically edited to eliminate the alpha-gal sugar molecule on pig organs, wich causes immediate rejection when the organs are transplanted into humans.
Though some suppliers have made many other genetic modifications to pig organs to lower the risk of rejection, the minimally edited organ performed surprisingly well for two months.
"At two months, the kidney was still functioning fine with no major problems," Sykes says. "It suggests that extensive genetic editing of the donor pig organ may not be as important as controlling the response from the patient's pre-existing T cells in recipients who do not have high levels of antibodies before the transplant."
Minimally edited pig organs are also easier to produce, promising a greater supply for patients than more rarefied pig organs.
Future directions
Though results from decedent studies may not apply to all xenotransplants in living recipients, there is a need to continue such studies. "Additional studies in decedents can help us improve xenotransplants," Sykes says.
"But it is a big sacrifice on the part of the family, and they must ultimately decide when the study stops. The family of the recipient in this study was very generous. What we've learned has been invaluable and will help us advance the science of xenotransplantation."
Additional information
The study, "Physiology and immunology of pig-to-human decedent kidney xenotransplant," by Robert A Montgomery and Jeffrey M. Stern, et al., was published in Nature on Nov. 13.
