The future looks bright for beta cell therapy in diabetes treatment

During the most recent Alberta Diabetes Institute (ADI) webinar in celebration of the 100th years of insulin discovery, expert speakers Gregory Korbutt, ’85 BSc, ’88 MSc, and Andrew Pepper discussed the current research on cellular therapy for Type 1 diabetes.

During the most recent Alberta Diabetes Institute (ADI) webinar in celebration of the 100th years of insulin discovery, expert speakers Gregory Korbutt, ’85 BSc, ’88 MSc, and Andrew Pepper discussed the current research on cellular therapy for Type 1 diabetes (T1D) treatment and the challenges faced by researchers in this field.

According to the International Diabetes Federation, diabetes cases are expected to increase around 51 per cent by 2045. T1D accounts for approximately 10 per cent of the total number of diabetes cases, and more than 300,000 Canadians suffer from this disease. One hundred years since its discovery, insulin is still the first line of therapy for T1D, but Pepper speculates Frederick Banting and Charles Best, the discoverers of insulin, would be excited about the promising future of beta cell replacement therapy to treat diabetes.

Here are the main messages taken from this webinar.

Challenges in islets transplantation

With the Edmonton Protocol, discovered at the University of Alberta about 20 years ago, pancreatic islets are transplanted from donors into patients with T1D, helping them to achieve insulin-independence. Although the protocol brought great advancement in T1D treatment, there are still challenges with this method, including the use of long-term immune suppressant drugs with systemic side-effects. In addition, the number of patients who need islet transplantation far outweighs the availability of donors, and the inflammatory reaction that occurs post-transplantation causes the loss of a considerable number of transplanted cells. Scientists are looking to improve the efficacy of islet transplantation, with the hope of reaching more people with better results.

Potential sources of beta cells and alternative transplantation sites

The current protocol for islet transplantation uses islets from cadaver donors, which are limited in number. To overcome the low numbers of islets available, other sources of beta cells are under investigation. These include human induced pluripotent stem cells (iPSC), human embryonic stem cells and islets from pigs. Each of these sources comes with its own challenges and manufacturing costs, affecting the production on a large scale. 

Transplantation sites outside the liver—such as subcutaneous devices containing beta cells—are also being tested as alternatives to improve transplant outcomes..  

Improvement of islet engraftment post-transplantation

The success of islet transplantation depends on the prevention of an autoimmune response, which causes transplant rejection. The toxicity of immunosuppressant drugs and the inflammatory process limits the efficacy of islet transplantation, so researchers are testing localized immunomodulation—in which microcapsules, injected with the islets during transplantation, release drugs locally over time—to prevent toxicity and delay rejection. Promising results seen in pre-clinical trials include delayed transplant rejection, improved glucose tolerance and reduced systemic immunosuppression.

Much work ahead

The future of beta cell therapy in diabetes treatment is exciting, but much work is still needed to bring this innovative therapy to patients. Meanwhile, current studies are helping to overcome the common downsides of islet transplantation and will serve as a basis to optimize a multi-drug approach to prevent autoimmune response post-transplantation and to find alternative sites to increase efficacy and efficiency of this process.

Every step in this direction is one step closer to improving the lives of millions of people around the globe.