American researchers have managed to transplant pancreatic cells capable of producing insulin without the risk of being rejected by the body since they are designed to go unnoticed by the patient’s immune system.
- The transplanted cells have been genetically modified to produce insulin on demand based on the level of glucose detected in the body.
- These cells are activated in the face of white blood cells capable of recognizing it and allow the islets to deactivate at the right time to go unnoticed.
- The next step for researchers is to move into human clinical trials.
Type 1 diabetes is characterized by the slow death of insulin-producing cells in the pancreas. This autoimmune disease most often occurs during childhood or adolescence. To circumvent this problem, American researchers have succeeded in creating insulin-producing cells designed to go unnoticed by the patient’s immune system. They thus avoid being destroyed and can be transplanted without risk of rejection. The results of the study were published on August 19 in the journal Nature.
Produce insulin on demand based on glucose levels
The islets of Langherans are the endocrine cells that secrete insulin in the pancreas and it is these that the researchers managed to recreate and successfully implant in mice. Without these islets, which gradually disappear in the patients concerned, glucose can no longer be stored correctly in the body, leading to hypoglycaemia and long-term risks of stroke, heart attack, kidney failure or even coma. To compensate for the lack of these cells, patients must inject themselves with insulin daily or undergo a transplant which is accompanied by lifelong immunosuppressants to prevent rejection of the graft by the immune system, but this increases the risks. of infections.
To circumvent the problem of defective insulin-producing cells, researchers at the Salk Institute in San Diego (United States) have managed to recreate three-dimensional islets of Langerhans in the laboratory. The cells that compose them have been genetically modified to produce insulin on demand according to the level of glucose detected in the body. This is possible thanks to a “genetic switch”, the ERR-gamma. “When we add the ERR-gamma, the cells have the energy to do their jobsays Michael Downes, co-author of the study. These cells are healthy and robust and can deliver insulin when they sense high glucose levels.”
A product that does not require any device
To evade the immune system, the researchers took inspiration from certain cancer cells. They have developed cells capable of producing a protein called PD-L1 at the right time. This has the particularity of being activated in the face of white blood cells capable of recognizing it and thus allowing the islets to deactivate at the right time to go unnoticed. “By expressing PD-L1, which acts as an immune blocker, transplanted organoids are able to hide from the immune system”, confirms Eiji Yoshihara, first author of the study. This system enabled transplanted mice to successfully control their blood sugar for 50 days.
The next step for researchers is to move into human clinical trials. Tests over a longer period will be carried out on mice in order to verify the duration of action of the transplanted organoids. “We now have a product that could be used in patients without the need for any device”, rejoices Professor Ronald Evans who participated in the study.
