Type 1 Diabetes (T1D) arises when a person’s own immune system mistakenly kills the insulin-producing beta cells in the pancreas. Beta cells normally produce insulin in a highly regulated manner to control blood sugar levels. Without these cells to regulate blood sugar levels, high or very low blood sugar levels can cause nerve damage, kidney damage, blindness, heart, and circulation problems—and without insulin treatment, even death. Insulin has saved millions of lives by turning diabetes from a death sentence to a chronic illness. But even with the best possible insulin administration, glucose is not perfectly controlled. Patients remain at risk for life-threatening long-term complications, not to mention the impact of constant monitoring of glucose, dietary restrictions and multiple daily insulin injections on their quality of life. While pharmaceutical insulin can control Type 1 diabetes, it does not replace the insulin-producing beta cells. Treatment, therefore, is an ongoing daily process.
Patients must monitor their dietary intake very closely; they must either inject themselves frequently with pharmaceutical insulin, or suffer serious side effects and damage to their bodies as a result of blood sugar reaching toxic levels. In the United States alone, Type 1 diabetes patients self-administer 11 million insulin injections daily to manage their illness. The estimated cost of diagnosed diabetes is $245 billion, a 41% increase over the last 5 years. In addition to the large financial cost of T1D, the personal burden of the disease on patients and their families is tremendous.
With the support of the California Institute for Regenerative Medicine (CIRM), researchers have begun to explore a revolutionary concept: what if, instead of trying to replace the function of the beta cells by injecting insulin, we could replace the lost beta cells themselves?
A group of pioneering scientists at ViaCyte, in collaboration with the University of California, San Francisco, is attempting to do just that, taking an innovative approach to treat T1D using embryonic stem cells. Their work is jointly funded by CIRM and the International Juvenile Diabetes Research Foundation (JDRF).
After many years of work, the ViaCyte-UCSF scientific team perfected a recipe to turn human embryonic stem cells into pancreatic progenitor cells, which are capable of maturing into fully functional, insulin-producing beta cells, as well as other cells
important to pancreatic function.
In order to deliver these cells into the body, ViaCyte scientists have also engineered an encapsulation device designed to keep immune cells out, protecting the cells inside from destruction while allowing the free flow of oxygen, nutrients, sugar, and proteins. Cells inside the device are able to sense glucose and respond by producing insulin, which easily exits into the blood. This system is called the VC-01 product candidate. In animal models, the implanted VC-01 product functionally cures experimental diabetes.
In September 2014, a human clinical trial began at University of California, San Diego. The goal of this trial is to find out if the VC-01 product is safe and can regulate blood sugar levels in humans like it has in mice. The results of this trial will be pivotal, and may be important next steps towards revolutionizing the way we approach diabetes treatment.
The VC-01 concept was born from the vision that stem cells can be used to replace any specialized cells that are missing in disease. Advancing this vision has only become possible in the last 10 years. Thanks in large part to funding for stem cell research from the CIRM and JDRF, we have come a long way in a short amount of time.
1. T. Schulz et al. A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells. Public Library of Science One (2012), Vol 7, Issue 5, e37004. http://viacyte.com/wp-content/uploads/TSchulz-et-al.-2012.pdf
2. Kelly et al. Cell-surface markers for the isolation of pancreatic cell types derived from human embryonic stem cells. Nature Biotechnology (2011), 29: 750-756.http://viacyte.com/wp-content/uploads/Kelly_Nature_Biotech_07_2011.pdf
3. McCall et al. Are stem cells a cure for diabetes? Clinical Science (2010), 118: 87-97. http://viacyte.com/wp-content/uploads/McCall_-Science.pdf
4. Baetge. Production of ß-cells from human embryonic stem cells. Diabetes, Obesity and Metabolism (2008),10: 186-194. http://viacyte.com/wp-content/uploads/Baetge_20081.pdf
5. Kroon et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cell in vivo. Nature Biotechnology (2008), 26: 443-452. http://viacyte.com/wp-content/uploads/AU2-web.pdf
6. McLean et al. Activin A efficiently specifies definitive endoderm from human embryonic stem cells only when phosphatidylinositol 3-kinase signaling is suppressed. Stem Cells (2007), 25: 29-38. http://viacyte.com/wp-content/uploads/McLean-2007-Ly-paper.pdf
7. D’Amour et al. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nature Biotechnology (2006), 24: 1392-1401. http://viacyte.com/wp-content/uploads/DAmour_Nature_Biotech_10_2006.pdf
8. D’Amour et al. Efficient differentiation of human embryonic stem cells to definitive endoderm. Nature Biotechnology (2005), 23: 1534-1541. http://viacyte.com/wp-content/uploads/DAmour_Nature_Biotech_10_2005.pdf