- The Washington Times - Thursday, June 13, 2002

University of Florida researchers have shown that adult rat liver cells can differentiate into insulin-producing pancreatic cells, a development they are calling a "breakthrough" in diabetes research.

The scientists report that preliminary findings also indicate that when large amounts of the new pancreatic cells are injected into diabetic mice, they can reverse the animals' high blood-sugar levels and make them normal.

High blood sugar is the prime symptom of uncontrolled diabetes, which results from a pancreas that either does not work at all or works poorly and produces little or no insulin, which is needed to metabolize sugar and other food nutrients for energy. Insulin-dependent, or Type I, diabetes occurs when immune cells wage an autoimmune attack on insulin-producing cells in the pancreas, treating the vital organ as if it were an infectious disease.

The discoveries in this study raise the chance the liver someday could provide cells capable of producing insulin for patients with diabetes, say the researchers, whose work is published in this week's issue of the National Academy of Sciences' journal Proceedings.

That would be significant, as it is more "invasive and dangerous" to retrieve stem cells from the pancreas than from the liver, said Dr. Lijun Yang, a University of Florida pathologist who was the lead investigator in the study. Collaborating with her in the research were Ammon B. Peck and Bryon E. Petersen, who also work in the University of Florida pathology department.

In virtually every news report about stem cells the raw materials out of which more specialized tissues develop in the body it is said the cells could have implications in the treatment of life-threatening diseases such as diabetes, Alzheimer's and Parkinson's. But much less attention has been focused on why medical researchers believe that to be true.

In this study, University of Florida scientists isolated stem cells from a cultured adult rat liver and then placed them in a high-sugar solution. The cells began to make insulin, which is not something liver cells normally do.

Dr. Yang said she then borrowed six diabetic mice from a neighboring laboratory. Three were left untreated.

But in the other group of three, one mouse was given a high number of insulin-producing cells, and its blood-sugar levels dropped to normal within 10 days. Another two mice received much smaller numbers of cells and remained diabetic.

"Our major observation from this work is that adult stem cells from a nonpancreatic source can be pushed into becoming mature cells capable of producing and secreting insulin in response to glucose without genetically altering the mature cells," said Dr. Yang.

This stem cell finding is "quite exciting" she said, because this is more evidence that "adult stem cells have much greater flexibility than we first thought."

Dr. Yang noted that other researchers previously have shown that both adult bone-marrow stem cells and adult muscle stem cells can become neurons. "There is tremendous flexibility in adult stem cells," she said.

Researchers tend to be grateful anytime they can show the usefulness of adult stem cells, given the political debate over therapy using stem cells in embryos. Embryonic stem cells can evolve into any type of tissue. But the embryo is destroyed in order to obtain the stem cells, and some critics say that amounts to murder.

Mr. Peck previously reported research in the journal Nature Medicine that demonstrated Type I diabetes could be reversed in mice by nurturing adult pancreatic stem cells in a test tube until they grew into insulin-producing organs called islets of Langerhans; then injecting the islets just beneath the skin. The implanted islets soon produced enough insulin to regulate blood sugar effectively.

But Mr. Peck said in a statement that there is a "major shortage of available islet tissue for injection," so researchers have been seeking alternative sources of insulin-producing cells. "Adult stem cells appear to offer great promise for the production of an almost unlimited supply of insulin-producing cells and islets of Langerhans," he said.

Dr. Yang is eager to begin a large, 18-month animal study to determine how long these differentiated liver stem cells will survive and function as insulin-producing cells and precisely how effective they are in curing diabetes in mice or rats. But she says she has no money at this time and is waiting to learn if she will be receiving a grant from the National Institutes of Health. "I need $500,000," she said.

Mr. Petersen cautioned that it would be years before this therapy could be available for humans.

"In a perfect world, it would take maybe five years. In a real world, probably 10," he said in a telephone interview.

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