Stem cell-based therapy

According to data from the World Health Organization (WHO), millions of individuals worldwide are living with type 1 diabetes. This condition is marked by insufficient insulin production in pancreatic islet cells, requiring the daily administration of insulin to effectively manage the disease. The underlying cause of type 1 diabetes is a loss of insulin-producing beta-cells in the so-called islets of Langerhans of the pancreas. Most patients manage their blood glucose levels through insulin injections, which involves a lot of time and monitoring from the patients themselves and can have side effects.

Whole pancreas or islet transplantation from deceased donors have been explored as alternatives to regular insulin doses, yet demand far outstrips supply, standing in the way of wide application. “For many years, researchers have looked for ways of transplanting functional new islet cells into people with type 1 diabetes, so that they can produce their own insulin, thus freeing them from daily time-consuming insulin injections,” says Professor Eckhard Wolf, Chair of Molecular Animal Breeding and Biotechnology at the Gene Center Munich. Stem cell-based replacement therapy has emerged as a promising alternative approach to restore islet function in diabetic patients and is currently being tested in first-in-human clinical trials. The key components of this therapy are islet cells derived via the directed differentiation of donor pluripotent stem cells, a specific type of stem cell that has the ability to form a wide range of cell types.

While islet cell replacement delivers improved blood glucose management for patients, it is important to note that there is still a significant risk of side effects. The immune system of the recipient may respond to the newly transplanted islet cells leading to rejection. Currently, patients undergoing islet transplantation are faced with the use of long-term immunosuppression to prevent the rejection and subsequent destruction of the transplanted cells by their own immune system.

With the aid of a grant worth 2.25 million US dollars from the Juvenile Diabetes Research Foundation (JDRF), scientists from LMU, the Helmholtz Diabetes Center, and the Technical University of Munich (TUM) are now investigating methods for safeguarding transplanted islet cells from the recipient’s immune system, so that islet transplantations could become a realistic alternative to insulin therapy in the future for patients with type 1 diabetes. “We want to understand how the immune system’s rejection of stem cell derived islets is mediated and can be prevented in the recipient,” explains Wolf, one of the LMU scientists involved in the project.