Researchers Overcome Immune Rejection in Pioneering Pig Kidney Transplant

A significant advancement in xenotransplantation has emerged as researchers successfully addressed the immune rejection challenges associated with transplanting genetically modified pig kidneys into humans. This breakthrough is particularly vital given that over 800,000 Americans suffer from late-stage kidney disease, yet only 3 percent receive a transplant annually, according to the U.S. Centers for Disease Control and Prevention.

To expand the availability of donor organs, experts have turned to genetically engineered pig kidneys. These modifications aim to prevent the human immune system from recognizing the animal organ as foreign, thereby reducing the likelihood of rejection. Despite these advances, immune reactions in recipients can still lead to organ damage and failure post-surgery.

Groundbreaking Research at NYU Langone Health

The study, spearheaded by researchers at NYU Langone Health, involved the transplantation of a genetically modified pig kidney into a brain-dead recipient. This individual had a functioning heart and was on a ventilator, with his family generously donating his body for scientific research. Over a period of 61 days following the transplant, the team collected various samples, enabling them to investigate immune cell interactions in a way that is not possible with living patients or primates.

In their first report, published on November 13, 2023, in the journal Nature, the researchers created a comprehensive map of immune activity in both the pig kidney and the human recipient. They discovered that rejection was primarily driven by antibodies and T cells—both crucial components of the immune system. Once these immune responses were identified, the researchers successfully reversed rejection using a combination of FDA-approved drugs that mitigated both antibody and T cell activity. Notably, there was no indication of permanent damage or diminished kidney function following this intervention.

Dr. Robert Montgomery, the lead author and chair of the Department of Surgery at NYU Langone Transplant Institute, emphasized the importance of this study, stating, “Our results better prepare us for anticipating and addressing harmful immune reactions during pig-organ transplantation in living humans.”

Detailed Immune Analysis and Future Directions

The second report in Nature provided an in-depth examination of the immune responses observed during the study. The research team conducted a multi-omics analysis, integrating data on gene function, expression, and protein activity to better understand the complexities of the immune system’s response to the transplant.

By analyzing approximately 5,100 expressed human and pig genes in the xenograft, the authors identified various immune cell types, monitored their behavior over the two-month observation period, and documented the rejection process in daily snapshots. The findings highlighted three significant immune responses against the pig kidney on specific postoperative days, driven by different components of the immune system.

Dr. Eloi Schmauch, co-lead author of the study, noted that the researchers were able to detect immune attacks up to five days before any clinical signs became apparent. “Our multi-omics analysis uncovers various biomarkers that shows promise as an early-warning system for pig organ rejection,” he stated.

Dr. Brendan Keating, senior author of the study, reiterated the significance of these findings, saying, “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.”

Looking ahead, the team plans to explore the specific molecules targeted by the immune response using the extensive data generated from their analysis. Further studies involving other human decedents and live patients are necessary to validate these promising results.

The modified pig organ used in this research was supplied by Revivicor, a subsidiary of United Therapeutics. Funding for the studies came from several National Institutes of Health grants and private organizations, ensuring a robust financial backing for this groundbreaking research.

As the field of xenotransplantation progresses, these findings represent a hopeful step toward addressing the critical shortage of available organs for transplantation, potentially transforming the lives of countless individuals in need.