Unlocking the Beta Cell
Beta cells are the insulin-secreting cells of the pancreas. They are contained within islets (or islets of Langerhans) — cell clusters found within the pancreas. Islets are responsible for producing glucagon (alpha cells), insulin (beta cells), and somatostatin (delta cells). Destruction of the insulin-producing beta cells results in type 1 diabetes, so the search for a cure has focused on finding a healthy replacement for these cells.
One way to replace beta cell function and re-establish insulin independence is through a pancreas transplant. The procedure, however, is relatively rare. Only 426 pancreas transplants were performed in the United States in 2007, due both to a lack of available organs and to the risk of potential toxicity of the immunosuppressive drugs required post-transplant.
More common is the combined kidney-pancreas transplant, which 796 patients underwent in the same year. The reason kidney-pancreas transplants are more common than pancreas-only transplants is the strict regimen of immunosuppressant drugs required for any transplant procedure. People with type 1 diabetes are already at risk for autoimmune problems and are more prone to infections, so further suppression of the immune system is risky.
Organs for transplant are still in much greater demand than supply. According to the United Network for Organ Sharing, in 2007 the number of people on the waiting list for organ transplants was twice as much as the number of available donors.
However, because of the high incidence of chronic kidney failure in people with diabetes, the need for a kidney transplant is higher than in the general population. If a patient has developed end-stage renal disease and requires a kidney transplant and accompanying immunosuppressive therapy anyway, the logic is that doing a simultaneous pancreas transplant typically can't hurt and can only help in most cases.
The Edmonton Protocol
Since only 2 percent of the pancreas is composed of islets, a transplant of islets only is less invasive and has a much quicker recovery time than a full pancreas transplant. The Edmonton Protocol is a procedure for transplanting pancreatic islets into people with type 1 diabetes in an effort to reverse their diabetes.
The procedure, which was developed at the University of Alberta (Canada), involves infusing healthy, insulin-producing islets into the portal vein through a catheter. They are carried through the bloodstream to the liver, where they attach and begin functioning. The Edmonton Protocol also involves treating the patient post-transplant with a specialized steroid-free immunosuppressive cocktail of the drugs daclizumab, tacrolimus, and sirolimus.
Dr. James Shapiro, the lead researcher behind the Edmonton Protocol, first published the protocol and its remarkable success rates in the New England Journal of Medicine in 2000. Since that time, clinical trials of the procedure have expanded and are taking place in research institutions throughout North America.
Islet transplantation has been under development since 1976, when the first successful animal islet transplant was performed by Dr. Paul Lacy, a researcher funded by the Juvenile Diabetes Research Foundation (JDRF).
One of the major obstacles in widespread application of islet transplantation is an inadequate supply of islets. The Edmonton Protocol involves infusion of a larger volume of freshly harvested islets than previous islet transplantation methods used. In fact, two donated cadaver pancreases are required for each islet transplant procedure.
And in 2006, Shapiro made headlines again by joining forces with Kyoto University in the world's first living donor islet transplant. Given the shortage of donated organs in the United States and abroad, this is where stem cell research may hold a prominent role in the search for a cure.
In 2007, the Collaborate Islet Transplant Registry (CITR) reported one-year success rates (as measured by at least one episode of insulin independence of fourteen consecutive days or more) of 67 percent, a significant advance over dismal pre-Edmonton rates of less than 10 percent. However, at three years after the first islet infusion, only 16 percent of recipients remain insulin independent.
On a more promising note, those islet transplant patients who have eventually gone back on insulin tend to have less erratic blood glucose levels and fewer incidents of severe hypoglycemia. Still, many challenges remain in improving islet cell transplantation outcomes.