A new worldwide study presented at the ESOT Congress 2025 provides unprecedented insight into one of the most significant barriers to employing animal organs in humans: rejection by the human immune system. 

Dr. Valentin Goutaudier and his team from the Paris Institute for Transplantation and Organ Regeneration and NYU Langone Transplant Institute used advanced imaging techniques to find out how human immune cells attack transplanted pig kidneys. 

This approach enabled the investigators to create the most detailed molecular map of rejection in these experimental transplants. It was discovered that human immune cells were present throughout the pig kidney's filtering system following transplantation. Signs of antibody-mediated rejection, which happens when the immune system attacks the foreign organ using specific proteins called antibodies, appeared as early as Day 10 and reached their highest level by Day 33. The study monitored these immunological responses for up to 61 days. 

"Our findings provide the most precise molecular map yet of how the human immune system interacts with a transplanted pig kidney. Dr Goutaudier highlighted that by identifying certain immune cell behaviours and gene expressions, we can modify anti-rejection therapy and increase transplant viability. 

Rejection remains the most significant challenge in xenotransplantation, which is the act of transferring organs or tissues from animals into humans. According to the World Health Organisation (WHO), organ failure is a serious global health issue, with millions in need of life-saving transplants. In many nations, the demand for kidneys greatly exceeds the supply. 

The scarcity is particularly acute in the United States, where, according to the US Department of Health and Human Services, over 90,000 people are now on the waiting list for a kidney. Xenotransplantation is viewed as a possible answer to the dilemma, but only if rejection is carefully managed. 

In the study, researchers used advanced bioinformatics techniques to discriminate between human immune cells and pig structural cells in transplanted kidneys. This enabled them to precisely determine how immune cells infiltrated and damaged the tissue. 

Macrophages and myeloid cells, which are white blood cells engaged in early immunological defence and inflammation, were the most common immune cells observed at all time points. This study supports previous findings that they play a critical role in rejecting transplanted pig organs. 

The researchers also investigated specific therapies to decrease these immune responses. When used early on, these therapies effectively reduced the symptoms of immunological assault on transplanted tissue. This finding indicates a vital early "window" in which treatment may be most effective. 

"Understanding the specific immune interactions at a molecular level allows us to develop targeted interventions that can prevent rejection before it escalates," according to Dr Goutaudier. 

These discoveries come as the first US-based clinical trials of pig kidney transplants on living human recipients are expected to begin in 2025. Researchers hope that by combining genetic alterations in donor pigs with targeted anti-rejection medications, such transplants will become a routine, safe, and successful choice. 

Experts emphasise that there is still work to be done. Even with these promising results, any widespread use of genetically engineered pig organs in humans will require extensive safety and efficacy testing, including studies in broad patient populations. 

Nevertheless, the new study marks a significant step towards resolving a global health concern. By disclosing the specific chemical conflicts between human immune cells and donated pig kidneys, it paves the way for smarter, more successful medicines that could alter transplant medicine over the next decade.