OPPORTUNITIES IN ISLET TRANSPLANTATION
Advances in islet transplantation have been extraordinary since the procedure was attempted in the mid-1980s, when the rate of insulin independence at one year was around 10 percent. However, additional research is necessary to optimize the procedure and make it available to the broader range of type 1 diabetes patients.

Approximately 6,000 human pancreases are available each year in the U.S. for islet transplantation — far fewer than the number needed to treat the 30,000 new cases of disease, let alone the approximately 1-2 million existing type 1 diabetes patients. Researchers are developing renewable sources of insulin-producing cells for transplantation, as described below. At the same time researchers are working to: improve the efficiency of islet isolation; achieve insulin independence using islets obtained from one pancreas per recipient; and explore the potential of living-donor islet transplantation.

Islet transplantation, like transplantation of a solid organ such as the heart or liver, requires recipients to take a daily regimen of immunosuppressive drugs that prevent rejection. These drugs can have severe side effects and, generally, are not suitable for use in type 1 diabetic children. Additional research is needed to develop agents that allow long-term survival of transplanted islets or that enable patients to withdraw from the drugs without losing the new islets. Approaches to thwart immune recognition of transplanted islets by "encapsulating" islets to physically protect them from the immune system require further investigation.

BENEFITS OF THIS RESEARCH
Although islet transplantation in its current form can only be provided to a few individuals with the most severe form of type 1 diabetes, it is life altering therapy in the most positive way for those people. Despite the observation that insulin independence is often not permanent, the ability to control blood sugar levels with insulin shots is significantly improved and hypoglycemia unawareness is reversed, allowing patients to resume normal activities, such as driving a car without the fear of losing consciousness. In the long term, as islet transplantation protocols become safer and more routine, it may also be possible to extend the benefits of transplantation to the treatment of type 2 diabetes patients who have lost beta cell function.


OPPORTUNITIES IN CELL AND REGENERATIVE MEDICINE FOR TYPE 1 DIABETES
Integrating and expanding on recent advances in beta cell biology will help researchers reach the goals of developing a renewable, universal supply of insulin-producing beta cells for a safe and effective cell-based therapy and for developing therapeutics that regenerate beta cells for type 1 diabetes.

In order to develop a renewable beta cell source or find ways to regenerate such cells within the body, scientists must understand what makes a beta cell unique by mapping out the complex networks of signaling mechanisms that control normal beta cell development and function.

Researchers are capitalizing on progress in stem cell biology by exploring ways to coax immature embryonic stem cells into cells that produce and release insulin in response to glucose and developing robust, scalable processes that lend themselves to large-scale production.

It is critical to translate the tantalizing evidence of beta cell regeneration in animal models into clinical strategies for regenerating or expanding islet mass in human patients. Investigators have also found that the number of pancreatic islets increases in humans under certain conditions that include type 2 diabetes, obesity, and pregnancy. Understanding how new islets are formed under those circumstances in animals and humans could help identify potential drug targets to allow investigators to develop novel methods or drugs to regenerate islets in type 1 diabetes patients. Another promising approach involves the production of insulin-producing cells from organs that share the same developmental origins as the pancreas, namely the liver or the gut.

BENEFITS OF THIS RESEARCH
In type 2 diabetes, patients often "burn out" their beta cells over time and become reliant on insulin therapy, much like type 1 diabetes patients. Thus, both type 1 and type 2 diabetes patients will ultimately benefit from research to establish a renewable, safe, and reliable supply of beta cells for transplantation or a strategy to regenerate a patient's own cells. A replenishable source of beta cells would extend the benefits of transplantation to far more patients than can be treated with cadaveric islets. Alternatively, a strategy for regenerative therapy for type 1 diabetes could potentially be used to treat patients who may not prove to be suitable candidates for transplantation, such as children and adolescents, and could be used more efficiently than transplantation in the diabetes population.