Researchers at NYU Langone Health have identified and addressed a key challenge in xenotransplantation, the process of transplanting animal organs into humans. The study focused on genetically modified pig kidneys, which are being explored as an option to increase organ availability for patients with late-stage kidney disease. According to the U.S. Centers for Disease Control and Prevention, over 800,000 Americans have advanced kidney disease but only about 3 percent receive a transplant each year.
The team transplanted a gene-edited pig kidney into a brain-dead human recipient whose body was donated for research. Over 61 days, they collected samples from tissue, blood, and body fluids more frequently than would be possible in living patients or primates. This allowed them to observe immune responses during both tolerance and rejection episodes.
In findings published in Nature on November 13, researchers mapped immune activity between the human host and the pig kidney. They discovered that both antibodies and T cells played roles in driving rejection of the transplanted organ.
After identifying these immune reactions, the team successfully reversed rejection using a combination of drugs already approved by the Food and Drug Administration that target both antibody and T cell activity. There were no signs of permanent damage or decreased kidney function after this intervention.
“Our results better prepare us for anticipating and addressing harmful immune reactions during pig-organ transplantation in living humans,” said study lead author Robert Montgomery, MD, PhD, Professor of Surgery at NYU Grossman School of Medicine. “This sets the stage for more successful clinical trials in the near future.”
Dr. Montgomery also noted that their findings confirm a pig kidney can function as a replacement for a human one.
A second report published in Nature provided further detail through multi-omics analysis—a method integrating data on gene function, expression levels, proteins, and other factors—to understand complex immune mechanisms involved in rejection.
By measuring approximately 5,100 genes expressed by both human and pig cells within the transplanted organ over two months, researchers identified every type of immune cell present and tracked their behavior throughout rejection events.
Three main immune responses were observed: one driven by innate immunity on postoperative day (POD) 21; another led by macrophages (a specific white blood cell population) on POD 33; and finally a response dominated by T cells on POD 45. Researchers could detect these attacks up to five days before they became visible in tissue using blood biomarkers.
“Our multi-omics analysis uncovers various biomarkers that shows promise as an early-warning system for pig organ rejection,” said co-lead author Eloi Schmauch, PhD.
“The specific immune reactions revealed in our investigation provide clear pig and human targets for therapies to improve the success of xenotransplantation to address the dire shortage of available organs,” said senior author Brendan Keating, PhD.
Dr. Keating indicated that future work will focus on identifying molecular targets involved in these damaging immune responses using data from DNA, RNA, and protein analyses generated during this study. He added that further studies involving additional deceased donors or live patients are necessary to validate these results.
The gene-edited pig organ used was supplied by Revivicor (a United Therapeutics subsidiary). Funding came from multiple sources including National Institutes of Health grants as well as support from Yosemite, United Therapeutics, Imam Abdulrahman bin Faisal University, Vaisala Fund, Aarne Koskelon Foundation, Antti and Tyyne Soininen Foundation, and Finnish Cultural Foundation.
Disclosures indicate Dr. Montgomery consults with several organizations including ProCure On-Demand; Spanish Society of Transplantation; Transplant Society; LiveOnNY; National Kidney Foundation; Sanofi-Aventis U.S.; Lung Biotechnology (United Therapeutics); PBC BioMed; eGenesis; Recombinetics—with all relationships managed according to NYU Langone Health policies.
Senior authorship on related clinical studies included Megan Sykes at Columbia University while Brian Piening at Providence Health served as co-lead author on multi-omics work. Additional collaborators represented institutions such as Seer Inc., University Paris Cité, Cordelier Research Center Paris, Revivicor Virginia, United Therapeutics Maryland among others.
NYU Langone Health is recognized nationally for patient outcomes and has received top rankings from Vizient Inc. four years running among academic medical centers across the country. It offers comprehensive services across seven inpatient locations plus extensive outpatient facilities in New York area and Florida along with tuition-free medical schools in Manhattan and Long Island.
