Advancing Stem Cell-Based Therapy for Type 1 Diabetes

With a 2.25 million US dollar grant provided by the Juvenile Diabetes Research Foundation (JDRF), Prof. Matthias Hebrok, Prof. Heiko Lickert, and Prof. Carolin Daniel from the Helmholtz Munich Diabetes Center, and Prof. Eckhard Wolf from Ludwig Maximilian Universität München (LMU) are investigating methods to protect transplanted islet cells from the recipient's immune system, potentially offering an alternative to insulin therapy for individuals with type 1 diabetes.

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 the 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 Langerhans-Islets of the pancreas. Currently, most patients manage their blood glucose levels through insulin injections, which requires a lot of time and monitoring from the patients themselves and side effects may occur.

But what if it was possible to transplant new functional islet cells into type 1 diabetes patients, so they can produce their own insulin freeing them from daily insulin injections?

Whole pancreas or islet transplantation from cadaveric donors has been explored as alternatives to exogenous insulin, yet the demand far outstrips the supply thus prohibiting its wide application.

For many years, researchers have worked towards generating functional islet cells from stem cells of healthy human donors for cell replacement therapy. 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, thereby freeing the patients from daily time-consuming insulin injections.

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 replacement provides 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 in order to prevent the rejection and subsequent destruction of the transplanted cells from their own immune system.

Scientists from Helmholtz Munich now investigate methods of safeguarding transplanted islet cells from the recipient’s immune system, so islet transplantations could become a realistic alternative to insulin therapy in the future for patients with type 1 diabetes. With a grant of 2.25 million US dollars awarded by the Juvenile Diabetes Research Foundation (JDRF), the teams of Prof. Matthias Hebrok, Prof. Heiko Lickert and Prof. Carolin Daniel from the Helmholtz Munich Diabetes Center together with Prof. Eckhard Wolf from the Ludwig Maximilian Universität München (LMU) aim to understand how the immune system’s rejection of stem cell derived islets is mediated and can be prevented in the recipient.