Diabetes researcher's goal: Make insulin-producing cells in lab

January 29, 2013 | by agervais

As people diagnosed with type 1 diabetes know all too well, their disease is caused by their own immune system's destruction of insulin-producing cells in the pancreas. Treatments exist, but there is no long-term  cure.

Pancreas, highlighted In diabetes, the body destroys insulin-producing cells in the pancreas, highlighted here.

Insulin can stabilize blood sugar levels, but dosage is sometimes difficult to determine and manage, resulting in hypoglycemia. Over time, poor management of blood sugar levels can lead to kidney failure, cardiovascular disease and stroke.

Because nothing is as good as one’s own cells, some City of Hope investigators have been focused on finding a way to replace pancreatic cells destroyed by the disease. One method is through islet cell transplantation.

In this approach, pancreatic islets, which contain the insulin-producing cells, are transplanted from deceased donors to  patients with diabetes.  City of Hope investigators have conducted phase I clinical trials in this area and have been able to help patients decrease their use of insulin or become insulin independent for at least one year.

Still, this is a costly approach. It takes two donor pancreases to provide enough islet cells to conduct the procedure. Further, pancreases are in short supply. As a result, only 1 percent of those patients who would be eligible for islet cell transplantation are able to benefit from it. Thus, it is urgent that scientists be able to find other sources of insulin-producing cells.

Hsun Teresa Ku, Ph.D., an assistant professor in the Department of Diabetes and Metabolic Diseases Research,  is among the researchers studying the problem. She’s determined to produce islet cells in the laboratory, thereby decreasing reliance on donor pancreases.

Ku is delving into the roots of the disease, studying stem cells that are integral to creating a renewable supply of cells for transplantation.

Stem cells are able to both self-renew and mature into cells with highly specialized functions. Ku’s research indicates that it may be possible to promote the transformation of stem cells into pancreatic insulin-producing cells. If a successful method for creating insulin-producing cells can be established, there would  be a nearly unlimited source of these cells for transplantation, and the roadblock to cell therapy due to insufficient donor organs would be eliminated.

Ku recently won support for her work via a $60,000 grant from the Ella Fitzgerald Charitable Foundation. The award will advance Ku’s research activities and help her achieve her ultimate goal of moving these cells into clinical trials for type 1 diabetes.

In order to enhance the conversion of stem cells into insulin-producing cells, Ku will study molecular signals that may play important roles in adult stem cell self-renewal and maturation. She will be studying two signaling molecules, called Wnt and Notch. Wnt enhances self-renewal of adult pancreatic stem cells; inhibiting Notch signaling increases production of insulin.

Ku believes that by manipulating both the Wnt and Notch signals, she can increase the number of insulin-producing cells derived from adult stem cells.

Her work will have a significant impact on scientists’ understanding of the biology of adult pancreatic stem cells, and will enhance their ability to transform these cells into insulin-producing cells for the treatment of type 1 diabetes. The project has the potential to generate an unlimited source of cells for transplantation, facilitating the expansion of islet transplant treatment as a viable therapy for type 1 diabetes.

With diabetes now affecting more than 25 million people in the United States at a cost of $174 billion in disease treatment and management – representing roughly one out of every $10 spent on health care in the United States – the stakes are enormous.

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