In a recent article published in the journal Nature, an international consortium of researchers, including members from the Paris Institute for Transplantation and Organ Regeneration (PITOR) – Université Paris Cité/Inserm/AP-HP –, the University of Maryland School of Medicine, the University of Alberta, and NYU Langone Health, analyzes the lessons learned from the first clinical xenotransplantations of porcine organs (kidneys, hearts, livers, lungs). They propose a new approach to monitor and prevent the rejection of porcine grafts in humans.
Addressing the global organ shortage, recent advances in genomic editing have enabled the creation of genetically modified pigs whose organs largely evade the human immune system. Since 2021, several successful xenotransplantations have been performed, demonstrating that hyperacute rejection, a major obstacle, can be overcome. Graft survival, ranging from a few days to nearly nine months, proves the viability of this approach.
However, these successes have revealed new forms of immune injury to the graft, often invisible to conventional monitoring methods. The Nature article, titled "Multimodal precision diagnostics in clinical xenotransplantation," highlights the importance of integrating precision diagnostic approaches to identify these hidden mechanisms of rejection and graft damage earlier and with greater accuracy.
« The field has reached a historic milestone by demonstrating that genetically modified porcine organs can function in humans, » states Alexandre Loupy, director of PITOR. « The next challenge is to detect graft rejection and injury phenomena early enough to intervene effectively. Precision diagnostics could be the missing piece enabling xenotransplantation to become a widely accessible therapy. »
Multimodal diagnostic approaches have detected persistent activation of innate immunity, early episodes of human antibody-mediated rejection, complement-mediated injury to the graft, and molecular signatures that distinguish immunological rejection from ischemia-reperfusion injury. These discoveries pave the way for new therapeutic targets.
« Several of the most important discoveries from the first human xenotransplantations have come from advanced diagnostic platforms rather than conventional pathology, » explains Raphael P. H. Meier, co-first author of the study. « This suggests that the future of xenotransplantation will depend on our ability to integrate different sources of biological information within a unified clinical framework. »
The authors propose a four-pillar strategy: creating international databases, continuous and non-invasive patient monitoring, tissue diagnostic techniques combining histopathology and molecular profiling, and advanced research platforms integrating artificial intelligence. These tools aim to identify graft injury mechanisms in real-time and tailor treatments.
« The question is no longer whether porcine organs can function in humans, » concludes Erwan Morgand, co-first author of the study. « The real challenge now is to understand why grafts eventually fail and how to intervene before damage becomes irreversible. Precision diagnostic tools offer a concrete path to achieve this. »
Xenotransplantation, which involves transplanting cells, tissues, or organs from one species to another, could offer a sustainable solution to the organ shortage. The first clinical trials of kidney transplantation from genetically modified pigs received approval from the U.S. FDA in 2025.
