Robert Montgomery prepares a pig kidney for transplant into a brain-dead man in New York in July 2023.Credit: Shelby Lum/AP via Alamy
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 papers1,2 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.
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