A medical team at Hospital Universitario La Paz in Madrid has developed an experimental technique aimed at enabling the recipient’s body to tolerate a transplanted organ as if it were its own. The procedure, based on a “double graft”, combines organ transplantation with hematopoietic stem cells from the same donor, which undergo a purification process in the laboratory. The aim is to create a state of immune tolerance that could drastically reduce —and in some cases even eliminate— the immunosuppressive medication that patients need to take for the rest of their lives.

Antonio Pérez Martínez and Megan Sykes – MadMoviex / CNIO

The first results have been observed in two patients with particularly complex medical histories. One of them, who received a multivisceral transplant in 2020 after having rejected two previous transplants, has had a properly functioning graft for more than six years and now requires only a minimal dose of an immunosuppressive drug. Another patient, who had rejected three kidney transplants over two decades, received a kidney from his brother in 2021 using this technique and, more than five years later, the organ remains fully functional with greatly reduced medication. In both cases, tests have shown that the immune system recognises the new organ while remaining able to respond to external threats.

The project, led by doctors Antonio Pérez Martínez and Francisco Hernández-Oliveros, draws on decades of research into so-called mixed chimerism and the induction of immune tolerance. The Spanish National Transplant Organisation (ONT), which supported the project from its early stages, believes that, if the results are confirmed, the strategy could substantially change the lives of transplant patients, particularly children. Long-term immunosuppression is associated with side effects and, in addition, the limited lifespan of transplanted organs means that some patients have to undergo further transplants. Pérez Martínez wrote his doctoral thesis on the work of researcher Megan Sykes, one of the pioneers who revived the idea of inducing tolerance through early exposure to cells from another individual, a process known as transient mixed chimerism.

The researchers have already launched a phase I clinical trial involving another ten patients to assess the feasibility and safety of the procedure. For the time being, the technique is being used in living-donor kidney transplants, although the team hopes to extend it to other organs and centres through future multicentre trials. The scientific community considers the initial results promising, but stresses that its safety and effectiveness will need to be confirmed in a larger number of patients before it can become routine clinical practice. The ultimate goal is to develop a personalised therapy that can extend the survival of transplanted organs and reduce dependence on immunosuppressive treatments.

Source: Eldiario.es