In a groundbreaking study recently published in The Lancet, a research team from the University of Paris Cité, Inserm, and AP-HP, led by Professor Alexandre Loupy at the Multi-Organ Transplantation and Regenerative Medicine Institute (PITOR) in Paris, in collaboration with Professor Robert A. Montgomery’s team at the New York Transplantation Institute in the United States, has achieved a major breakthrough in the field of xenotransplantation.

Xenotransplantation, the transplantation of organs from genetically modified pigs into humans, has long held promise as a solution to the global organ shortage. Pigs, due to their physiological and morphological similarities to humans, are considered the ideal donor species. However, the presence of natural antibodies in the human bloodstream directed against pig cell surface antigens has historically led to hyperacute rejection, resulting in rapid graft failure.

Advancements in pig genome editing have now enabled the removal of genes responsible for these antigens, significantly reducing the risk of rejection. In late 2021, Professor Montgomery’s team successfully transplanted genetically modified pig kidneys into two brain-dead human patients. The remarkable outcome marked a significant milestone in the field.

The study, led by Professor Loupy, delved into the patients’ immune responses and revealed a unique form of rejection mediated by antibodies. Despite initial success, these findings underscore the need for a deeper understanding of the immune interactions between humans and pig organs in xenotransplantation.

The innovative approach employed advanced immunology and molecular microscopy technologies to precisely characterize immune cells within the transplanted organs. The results revealed a distinctive rejection pattern involving innate immune cells, a type of immunity shared across species, expressing genes typical of human organ rejection mediated by antibodies.

While this form of rejection poses challenges, it also provides valuable insights. Researchers can now identify molecular targets to optimize genetically modified pig models and develop immunosuppressive treatments. Existing treatments for antibody-mediated rejection in human transplantation may also be adapted for xenotransplantation.

This study opens promising avenues for successful xenotransplantation of genetically modified pig kidneys into living human recipients, with long-term graft survival. Professor Loupy’s team will continue to analyze xenotransplant biopsies, solidifying France’s leadership in xenotransplantation. These pioneering efforts offer hope that the global organ shortage may one day become a distant memory, thanks to the remarkable progress in the field.

Study available here