Researchers Use Embryonic Stem Cells to Treat Diabetes

Doctors may be one step closer to using stem cells to cure diabetes, according to a new study by researchers at the stem cell engineering company Novacell, Inc. in San Diego who report that they managed to convert human embryonic stem cells into insulin-producing cells.

Insulin is the chemical produced in the pancreas that allows the body to regulate blood-sugar levels — and it is precisely the substance that many of those with diabetes lack.

The researchers, who reported their findings in the journal Nature Biotechnology, found that when they injected these human cells into diabetic mice, the treatment alleviated diabetes in the rodents.

According to Dr. Emmanuel Baetge, primary study investigator and chief scientific officer at Novocell, Inc., the new technique used by his team will provide doctors with a bulk supply of clean, uncontaminated insulin-secreting cells for use in diabetes patients.

"This is a much more controlled process, and you basically are sure of getting the same quality of cell every time you do the implant," Baetge explained.

"Currently, a patient would have to wait and wait for a cadaver organ to become available, and even then there is a high risk of the cells from that organ being infected or contaminated," he said. "If we instead use embryonic stem cells then we can also make unlimited numbers of these cells and have an unlimited source that we can stockpile and have available whenever a patient is ready for it."

Stem cell experts not directly involved with the research agreed that it represents an exciting advancement.

"Theoretically, an infinite number of insulin-producing cells can be generated [using this technique]," said Dr. Curt Freed, director of the Neurotransplantation Program for Parkinson's Disease at the University of Colorado School of Medicine.

The Problems With Cell Transplants

Scientists derive human embryonic stem cells from human embryos or human fetal tissue. Because stem cells have the potential to grow into any one of the body's more than 200 cell types, diabetes researchers have been searching for decades for a way to grow stem cells into insulin-producing cells — which, in those with diabetes, are destroyed by the patient's own immune system.

The only similar treatment currently in use for diabetes involves injecting patients with pancreatic islet cells — the cells in the pancreas that secrete insulin and other hormones. These are usually harvested from cadavers.

However, any time a new cell is introduced into the body, our immune system treats it as any other foreign invader and attempts to reject it.

Thus, patients receiving islet cell transplants are required to also receive medications that reduce their immune response to prevent rejection of the cells. As a result, less than 8 percent of islet cell transplants performed before last year were successful, according to the National Institutes of Health (NIH).

An Endless Stockpile of Cells

With this new method, scientists were able to grow insulin-producing cells in mice after about one to three months.

The advance comes at a time when diabetes affects more people and causes more deaths each year than breast cancer and AIDS combined, according to NIH statistics. Diabetes is the seventh leading cause of death in the United States, with nearly 200,000 deaths reported each year. The American Diabetes Association estimates that nearly 16 million people, or 5.9 percent of the U.S. population, currently have diabetes.

Because there is a constant shortage of cadaver islet cells available for transplant, many experts believe having a "stockpile" of islet cells derived from embryonic stem cells would immensely benefit a huge number of diabetes patients.

"Islet cell transplants will always be extremely limited," Freed said. "It is my understanding that the islets from the pancreases of two cadaver donors are needed to treat one diabetic person."

According to Dr. Jeffrey Bluestone, director of the University of California at San Francisco Diabetes Center and board member for Novocell, Inc., there are too few pancreases available and, such being the case, islet cell transplants are limited to those patients with "Brittle" diabetes, meaning that they have had diabetes for such a long time that they can no longer distinguish the symptoms of hypoglycemia, or low blood sugar.

"Also, the patients [receiving islet cell transplants] need to be small — usually 150 pounds or less — because of the limited number of islets that can be obtained from each cadaveric pancreas," Bluestone said. "So, in general, a greater source of islets would have a very positive effect for the many diabetics in need of transplantation."

Hurdles Remain

But despite the enormous potential for this technique to free possibly millions of Americans from their diabetes, some experts remain doubtful that this technology will be available to the public any time soon.

Many diabetes and stem cell experts believe there are a number of hurdles to overcome before this technique could replace the traditional method of transplanting islet cells from cadaver organs.

Dr. Anne Peters, director of University of Southern California's Clinical Diabetes Programs, said this study fails to provide an answer for one of the most pressing issues faced by any diabetes patient receiving any form of islet cell transplantation: What guarantee would doctors have that the transplanted insulin-producing cells would not be destroyed by the body, just as the diabetic patient's own cells were?

"What would happen to these cells in that environment?" Peters said.

Also, just as with current methods of islet cell transplantation, the body will still recognize the insulin-producing cells grown from human embryonic stem cells as being foreign. Therefore, diabetes patients undergoing this new technique will still require immunosuppressant therapies, most of them for their entire lives.

Moreover, one of the biggest concerns about injecting patients with embryonic stem cells is that these cells have the potential to develop into cancerous tumors.

"The study does show that these [human embryonic stem cells] might have developed to a point where they appear to be no longer [tumor-forming]," said Dr. Bryon Petersen, associate professor in the department of pathology at the University of Florida College of Medicine. "This is a good thing, but what needs to follow is just how long will these cells stay fully differentiated — to make these cells no longer a threat to the patient's long-term health."

But despite the hurdles that scientists face, there is little doubt that these findings have opened countless doors for research on diabetes and other genetic diseases.

"This is an extraordinary breakthrough by scientists at Novocell," Freed said. "This discovery holds promise for everyone with insulin-requiring diabetes. While outcomes of clinical trials are unpredictable, these cells are likely to be tested in patients soon."

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