Gel particles against rejection
Researchers at Georgia Tech University, the University of Louisville and the University of Michigan have developed a method of influencing key cells of the immune system, ensuring their tolerance to transplanted insulin-producing islets of Langerhans. If the results obtained in experiments on mice are confirmed in clinical studies, the approach proposed by the authors will allow the treatment of type 1 diabetes mellitus without long-term complications of immunosuppression.
The new method involves the introduction of synthetic hydrogel particles to the patient simultaneously with donor insulin-producing islands, presenting a protein known as a Fas ligand (FasL) to immune T-effector cells. Effector T lymphocytes are responsible for rejection of donor transplants and, after activation, express the Fas receptor, which makes them susceptible to Fas-mediated apoptosis (cell death).
As part of the experiment, Fas-ligand presenting particles were mixed with live Langerhans islands and injected into mice with chemically induced diabetes mellitus under a renal capsule or into epididymal adipose tissue – an analogue of the omentum in humans. To retain cells and gel particles in the transplantation zone, they were injected into a capsule made of biodegradable polyethylene glycol hydrogel, which gradually releases endothelial growth factor, which promotes the engraftment of islets.
The presence of Fas-ligand-presenting particles in the graft ensured the development of local tolerance to foreign material. At the same time, the recipients developed a normal systemic immune response to the introduction of donor antigens. A short course of the immunosuppressant rapamycin further enhanced the immunomodulatory effect of Fas-ligand-bearing particles. As a result, the transplanted islets remained in the body and did not cause the development of a rejection reaction for more than 200 days.
According to the authors, the hydrogel can be prepared two weeks before transplantation and used with any donor islets of Langerhans. They plan to test its effectiveness in conditions of more complex immune systems and for longer periods of time. They also hope that the scope of the developed approach will not be limited to the transplantation of Langerhans islets and over time it will demonstrate its effectiveness in bone marrow transplantation, as well as donor organs.
Article by Devon M. Headen et al. Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance published in the journal Nature Materials.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Georgia Institute of Technology: Biomaterial Particles Educate Immune System to Accept Transplanted Islets.