November 17, 2025
3 min read
Transplant Rejection Is a Major Hurdle for Pig Organs. Scientists Are Solving the Problem
In a successful transplant in a man with brain death, scientists prevented the immune system from attacking a genetically modified pig kidney for 61 days, the longest such an experiment has lasted
Robert Montgomery prepares a pig kidney for transplant into a brain-dead man in New York in July 2023.
Scientists have successfully stopped a pig kidney from being rejected by its human recipient. The organ survived for 61 days in the recipient, a 57-year-old brain-dead man in the United States, the longest a genetically modified pig organ has survived in a brain-dead person.
In two papers published in Nature today, researchers describe the main factors that cause the human immune system to reject transplanted organs. Researchers say the findings will improve outcomes for living people who receive organs from other people, or from animals.
“In my mind, this is the first evidence of how to reverse rejection,” says Muhammad Mohiuddin, a clinician researcher at the University of Maryland School of Medicine in Baltimore, who led the first pig-heart transplant into a living person in 2022.
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In the past three years, around a dozen living people have received organs from genetically modified pigs, including hearts, kidneys, livers and a thymus. But most of these organs were eventually removed after losing function or no longer providing enough benefit to justify the immunosuppression treatment required. Other recipients died shortly after the transplant.
Along with the pig kidney, the male recipient also received the pig’s thymus, a small gland that taught the man’s immune system to recognize the pig’s cells as part of the body. The thymus probably played a big role in helping the pig organ survive for longer, says co-author of the studies, Robert Montgomery, a surgeon and researcher at the New York University Langone Transplant Institute in New York City. In past experiments with non-human primates, he says, the modified kidney survived better when transplanted with the thymus than without it.
Avoiding rejection
The latest pig-organ transplant was performed on 14 July 2023 at New York University Langone in New York City. The kidney and thymus were taken from a pig supplied by Revivicor, a subsidiary of biotechnology firm United Therapeutics, based in Virginia. The pigs had a single genetic modification, removing gene GGAT1, to stop the production of a sugar called alpha-gal on cells. Alpha-gal has been found to cause organ rejection in transplant surgeries in non-human primates.
Immediately after the transplant, the kidney appeared healthy and produced urine. But 33 days after the procedure, the kidney’s function suddenly declined, and a biopsy showed that the organ was being rejected and damaged by antibodies. The team replaced the person’s plasma and gave them steroids and a drug called pegcetacoplan, which stopped pig cells being tagged for destruction by the immune system. But on day 49, another biopsy showed a different type of rejection, in which inflammatory cells had infiltrated the kidney’s surface. This was treated with an immunosuppressant that destroys T cells and stopped the organ from being rejected. Kidney function was also fully restored. The research team chose to end the experiment at 61 days.
Immune system investigation
Following the transplant, the team also analysed the person’s blood to map how the immune system responded on a molecular level. They showed that the pig kidney increasingly expressed genes associated with rejection, such as CXCL9, CXCL10 and CXCL11, and their expression decreased after the rejection was stopped. High levels of macrophages and natural killer cells, a type of T cell, which are part of the innate immune system, were observed on day 33. Mohiuddin says this suggests that T cells play a more prominent role in rejection than was previously thought. He adds that analysing the transplant recipient’s blood could help clinicians to identify and treat rejection early.
Montgomery says the case could also inform which pig genetic modifications are necessary. Most pig organs come from pigs that have had at least 10 genetic modifications to reduce the risk of rejection. Montgomery says only removing GGATI was enough to prevent immediate organ rejection. Scientists can breed pigs with this modification, whereas pigs with multiple modifications need to be cloned, he adds.
But Montgomery and his colleagues acknowledge that the efficacy of using organs from pigs with minimal genetic edits needs to be validated in further experiments in brain-dead and living people. His team are working on clinical trials with United Therapeutics. They have previously transplanted a kidney with the same modification into one living person, which failed within two months owing to the recipients’ pre-existing heart failure.
This article is reproduced with permission and was first published on November 13, 2025.
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