100 years ago, researchers purified insulin and transformed the lives of people with diabetes. Breakthroughs in stem cell research are providing potential opportunities to transform the next 100 years of treatment.

While technology has certainly improved, people with type 1 diabetes (T1D) conceptually treat their disease in much the same way as patients were treated a century ago. People with T1D lack insulin, a hormone required to process sugar into energy. To survive, patients must replace this insulin. For the last 100 years, diabetics have injected themselves multiple times a day with insulin using a syringe or a pump, but today, scientists are attempting to revolutionize this treatment using stem cells.   

T1D is an autoimmune disease where the body kills the cells in the pancreas that normally make insulin to control blood sugar levels, known as β (beta) cells. Unfortunately, the pancreas cannot regenerate β cells, and consequently people with T1D must rely on supplemental insulin for their entire lives. This process is not as precise as having functional β cells and reliance on lifelong insulin has tremendous health and economic burdens.

Scientists are working to use stem cells to replace β cells and provide a new type of treatment. Pluripotent stem cells are a versatile type of stem cell that can be coaxed into most cell types found in our bodies, including pancreatic β cells. Researchers have succeeded in turning stem cells into β cells, which can now be transplanted into patients to produce the necessary insulin. If this treatment is successful, it could potentially cure people of T1D, and the patients would no longer need to inject themselves with insulin (learn more in this short video from the Harvard Stem Cell Institute, USA).

The process of turning stem cells into β cells in the laboratory is sophisticated. Scientists working in the lab first had to determine how to replicate the way the pancreas develops in the human body. Given the limited knowledge of human fetal development, stem cell biologists conducted many studies to determine the specific genes that regulate β cell development in humans. During the last 15 years, several research groups have independently used this information to successfully make β cells from stem cells, creating a path forward for stem cell-based T1D treatments.

Strikingly, researchers found that β cells derived from stem cells in the lab can perform the key functions of their counterparts found in the human body, including making insulin in response to sugar. When transplanted into diabetic mice, stem cell-derived β cells can regulate sugar metabolism and improve the mouse’s diabetic condition. Importantly, the mice survive without supplemental insulin – an important preclinical result that set the stage for clinical trials.      

Last year, the U.S. Food Drug Administration (FDA) approved the first clinical trial of a pluripotent stem cell-based therapy for treating T1D. Initiated by ISSCR past-president Douglas Melton, PhD, Harvard University, USA and Vertex Pharmaceuticals, this trial tests whether transplanting stem cell-derived β cells in people with T1D is effective and safe.

In October 2021, the scientific team carrying out this clinical trial reported initial positive results from their first patient, Brian Shelton. After relying on supplemental insulin for about 40 years, Brian was able to produce his own insulin 90 days after receiving a single infusion of stem cell-derived insulin-producing β cells, nearly eliminating his dependency on insulin injections.

In an alternative approach to transplanting mature β cells, another biotechnology company, ViaCyte, is transplanting what are called stem cell-derived precursor cells, which mature and become functional once in the human body. The unique aspect of this strategy is that the immature cells have the ability to develop into β cells as well as other cell types that regulate sugar metabolism.

ViaCyte released preliminary results from its clinical trial in December 2021. The company reported on 15 patients and saw that the transplanted stem cell-derived precursor cells did indeed mature into cells that regulated sugar metabolism in people with T1D.

Together, these initial clinical trial results demonstrate the potential to use stem cell-derived cell products to treat people with T1D.

Before these therapies receive approval outside of clinical trials, further studies are necessary. It is important to test these treatments in more patients, examine possible long-term effects, and better protect the transplanted cells from attack by the patient’s immune system. 

These achievements in stem cell research are important milestones that move us closer to a cure for T1 diabetes and that have the potential to benefit the estimated 9 million people worldwide like Brian who are living with the chronic disease.

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Blog by guest contributor S.C. Jacky Sun, PhD candidate in the labs of Ed Stanley and Andrew Elefanty at the Murdoch Children’s Research Institute, Melbourne.