In May 2022, the first patient in the world to receive a heart transplant from a genetically modified pig survived two months. At 57, he suffered from end-stage heart failure and arrhythmia. Scientifically, this patient underwent a xenotransplantation – that is to say a surgical procedure aimed at transplanting a healthy graft into a patient from a biological species different from that of the recipient. In this specific case, a man received an organ from a pig.
More recently, a study, published on August 18, 2023 in the scientific journal The Lancet, elucidated the mechanisms involved in the immune response occurring after the transplantation of genetically modified pig kidneys in humans.
The “Multidimensional Approaches in Organ Transplantation” research team from Paris Cité University, Inserm and AP-HP, led by Prof. Alexandre Loupy at the Institute of Multi-Organ Transplantation and regenerative medicine Pitor de Paris, in collaboration with the NYU Langone Health Institute in the United States, has identified therapeutic solutions to prevent rejection of the transplanted organ.
Organ donation suffers from a shortage and France is struggling to convince donors. As of January 1, 2023, 10,810 patients were on the active waiting list for all organs combined. Faced with this tense situation, xenotransplantation represents a promising solution. The choice of pig is not random as this animal is considered the ideal donor species due to many morphological similarities between pig and human organs.
“Their use has historically been limited by interspecies immunological barriers, in particular by the natural presence in the human bloodstream of antibodies directed against xenoantigens present on the surface of porcine cells, responsible for a hyperacute rejection phenomenon which inexorably leads to graft loss within minutes,” the researchers report.
“This is a true revolution in transplantation and in the medical community in general. What once sounded like science fiction has now become reality thanks to biotechnologies that have made it possible to prevent hyperacute rejection. However, the immune response of patients receiving this type of transplant had not yet been characterized. However, this is essential to increase the chances of success of the xenograft. We therefore designed a study and brought together a multidisciplinary group of experts to decipher these complex phenomena of xenograft rejection in humans,” says Prof. Alexandre Loupy, PU-PH, nephrologist at Necker Hospital (AP-HP) , world expert in rejection.
For what results? Researchers found that patients showed early signs of a form of rejection that were nearly invisible with standard microscopy technologies. “We have demonstrated a very particular form of rejection, sharing both molecular characteristics of an intraspecies and interspecies immune response. The localization of the inflammatory cells was also unusual, as they were mainly concentrated in porcine glomeruli, i.e. kidney blood filters, whereas they are classically distributed throughout the circulation of grafts in human transplantation,” reports Dr. Alessia Giarraputo, researcher and co-first author of the study.
