Stem Cells and Diabetes

Diabetes exacts its toll on many Americans, young and old. For years, researchers have painstakingly dissected this complicated disease caused by the destruction of insulin producing islet cells of the pancreas. Despite progress in understanding the underlying disease mechanisms for diabetes, there is still a paucity of effective therapies. For years investigators have been making slow, but steady, progress on experimental strategies for pancreatic transplantation and islet cell replacement. Now, researchers have turned their attention to adult stem cells that appear to be precursors to islet cells and embryonic stem cells that produce insulin.

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Stem Cells and Diabetes 

Introduction

For decades, diabetes researchers have been searching for ways to replace the insulin-producing cells of the pancreas that are destroyed by a patient's own immune system. Now it appears that this may be possible. Each year, diabetes affects more people and causes more deaths than breast cancer and AIDS combined. Diabetes is the seventh leading cause of death in the United States today, with nearly 200,000 deaths reported each year. The American Diabetes Association estimates that nearly 16 million people, or 5.9 percent of the United States population, currently have diabetes.

Diabetes is actually a group of diseases characterized by abnormally high levels of the sugar glucose in the bloodstream. This excess glucose is responsible for most of the complications of diabetes, which include blindness, kidney failure, heart disease, stroke, neuropathy, and amputations. Type 1 diabetes, also known as juvenile-onset diabetes, typically affects children and young adults. Diabetes develops when the body's immune system sees its own cells as foreign and attacks and destroys them. As a result, the islet cells of the pancreas, which normally produce insulin, are destroyed. In the absence of insulin, glucose cannot enter the cell and glucose accumulates in the blood. Type 2 diabetes, also called adult-onset diabetes, tends to affect older, sedentary, and overweight individuals with a family history of diabetes. Type 2 diabetes occurs when the body cannot use insulin effectively. This is called insulin resistance and the result is the same as with type 1 diabetes—a build up of glucose in the blood.

There is currently no cure for diabetes. People with type 1 diabetes must take insulin several times a day and test their blood glucose concentration three to four times a day throughout their entire lives. Frequent monitoring is important because patients who keep their blood glucose concentrations as close to normal as possible can significantly reduce many of the complications of diabetes, such as retinopathy (a disease of the small blood vessels of the eye which can lead to blindness) and heart disease, that tend to develop over time. People with type 2 diabetes can often control their blood glucose concentrations through a combination of diet, exercise, and oral medication. Type 2 diabetes often progresses to the point where only insulin therapy will control blood glucose concentrations.

Each year, approximately 1,300 people with type 1 diabetes receive whole-organ pancreas transplants. After a year, 83 percent of these patients, on average, have no symptoms of diabetes and do not have to take insulin to maintain normal glucose concentrations in the blood. However, the demand for transplantable pancreases outweighs their availability. To prevent the body from rejecting the transplanted pancreas, patients must take powerful drugs that suppress the immune system for their entire lives, a regimen that makes them susceptible to a host of other diseases. Many hospitals will not perform a pancreas transplant unless the patient also needs a kidney transplant. That is because the risk of infection due to immunosuppressant therapy can be a greater health threat than the diabetes itself. But if a patient is also receiving a new kidney and will require immunosuppressant drugs anyway, many hospitals will perform the pancreas transplant.

Over the past several years, doctors have attempted to cure diabetes by injecting patients with pancreatic islet cells—the cells of the pancreas that secrete insulin and other hormones. However, the requirement for steroid immunosuppressant therapy to prevent rejection of the cells increases the metabolic demand on insulin-producing cells and eventually they may exhaust their capacity to produce insulin. The deleterious effect of steroids is greater for islet cell transplants than for whole-organ transplants. As a result, less than 8 percent of islet cell transplants performed before last year had been successful.

More recently, James Shapiro and his colleagues in Edmonton, Alberta, Canada, have developed an experimental protocol for transplanting islet cells that involves using a much larger amount of islet cells and a different type of immunosuppressant therapy. In a recent study, they report that [17], seven of seven patients who received islet cell transplants no longer needed to take insulin, and their blood glucose concentrations were normal a year after surgery. The success of the Edmonton protocol is now being tested at 10 centers around the world.

If the success of the Edmonton protocol can be duplicated, many hurdles still remain in using this approach on a wide scale to treat diabetes. First, donor tissue is not readily available. Islet cells used in transplants are obtained from cadavers, and the procedure requires at least two cadavers per transplant. The islet cells must be immunologically compatible, and the tissue must be freshly obtained—within eight hours of death. Because of the shortage of organ donors, these requirements are difficult to meet and the waiting list is expected to far exceed available tissue, especially if the procedure becomes widely accepted and available. Further, islet cell transplant recipients face a lifetime of immunosuppressant therapy, which makes them susceptible to other serious infections and diseases.