Clinical Research News

The Search for a Cure: Islet Cell Transplantation for Type 1 Diabetes

The past few years have heralded remarkable improvements in the management of type 1 diabetes. Physicians and researchers at Columbia, however, are pushing to move past successful control of the disease, and reach for a cure. One promising experimental procedure, islet cell transplantation—currently in the clinical trials stage—may offer a vital step forward in this quest.

Named after Paul Langerhans, the German scientist who discovered them in 1869, the Islets of Langerhans are clusters of cells in the pancreas that produce hormones.Within the islets, the alpha cells make glucagon, a hormone that raises the level of glucose in the blood, while the beta cells make insulin, which helps the body convert food into energy. In type 1 diabetes, the body's immune system destroys the insulin—producing islet cells. As a result, people who have type 1 diabetes must monitor their blood sugar levels and take regular insulin injections.

(left) Appearance of human pancreatic islets in whole pancreas. (right) Isolated human islets prepared for injection into patient

A complex procedure, islet cell transplantation involves removing islets from a donor pancreas and transferring them into the diabetic patient's liver. Interestingly, islets not only have the ability to grow in the liver, they can also adapt the liver to function as a back-up pancreas. If the procedure is successful, the liver assumes responsibility for regulating blood sugar and producing insulin. Researchers believe islet cell transplantation could completely eliminate the need for insulin injections from the lives of most people with type 1 diabetes—which would be a major breakthrough in the treatment of the disease.

A Minimally Invasive Alternative

Islet transplantation was originally developed as an alternative to pancreas transplantation—a major procedure in which the diabetic patient receives a donor pancreas to replace the damaged organ. Typically, physicians perform a pancreas transplant at the same time as a kidney transplant in patients with diabetesrelated kidney failure. Islet cell transplantation offers a minimally invasive way to achieve the same goal—production of insulin by the patient.

"The major advantage of a pancreatic islet transplant is that it does not involve any kind of major surgery. The procedure of islet transplantation is done by inserting a small needle into the liver, and injecting a fluid solution containing the islets into the liver. It can take less than an hour and can be done using a local anesthetic. It also does not have the risk of post—operative complications, such as inflammation of the pancreas," says Mark A. Hardy, MD, Auchincloss Professor of Surgery at Columbia and Surgicial Director of Pancreatic Islet Transplantation at Columbia University Medical Center.

While Dr. Hardy believes the procedure holds enormous promise for patients with type 1 diabetes, he also emphasizes that it is an experimental procedure which must overcome certain obstacles. "The disadvantage is that you need human pancreases, and donors are a very scarce resource," he explains. "The islet isolation procedure is also relatively complicated. In addition, rejection is an obstacle with any transplant. Immunosuppressive drugs are needed to keep the transplanted islets functioning."

Perfecting the Procedure

• Collecting islet cells from animal donors
• Developing procedures to make human stem cells function as islet cells
• Growth of potential islet cells from bone marrow
• Making islets multiply through genetic engineering

While the procedure remains available at only a few specialized centers such as Columbia, recent outcomes have been very positive. Some patients have been able to stop injecting insulin within a year of the transplant, and no longer have the extremely high blood sugar levels seen in uncontrollable type 1 diabetes.

Dr. Hardy and Kevan C. Herold, MD conducted their first islet cell transplant in January 2004. "We're going through an evolution, which is very exciting," Dr. Hardy says. "I believe islet transplantation will replace whole organ transplantation one day. I think this is one of the few instances where cellular transplantation will replace organ transplantation. The signs all point to more progress."

The winter 2004 issue of our award-winning educational newsletter, "healthpoints," was dedicated to the topic of diabetes. To view a complete pdf of the issue, please click here.