Liver Delivers Insulin-Producing Cells in Rats

First time stem cells from organ other than pancreas coaxed to do job

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By
HealthDay Reporter

MONDAY, June 3, 2002 (HealthDayNews) -- A diabetic's own liver may one day be the source of his salvation by supplying lost pancreatic cells that normally produce insulin.

Florida researchers have found that stem cells in adult rat livers can be coaxed into becoming specialized pancreatic tissue that produces the critical sugar-processing hormone both in a dish and in animals. Although yet to be repeated in people, the discovery is potentially important for patients with diabetes who can't generate enough insulin to handle the glucose they ingest.

Over time, failure to control blood sugar can lead to heart attacks, strokes, blindness, kidney failure, and myriad other complications.

Matt Petersen, director of diabetes information resources at the American Diabetes Association, called the work "very promising." The advantage of using one's own liver as a factory for new pancreatic tissue is clear: Unlike grafts from other people, the immune system won't immediately reject the new cells, Petersen said.

Even so, the study doesn't address the fundamental problem of why people with diabetes lose their insulin-producing islet cells to begin with. "Presumably, the body would go ahead and destroy these new cells, too," Petersen said. However, there's hope here, as well, because researchers are trying to find ways to disarm the auto-immune attack.

An estimated 17 million Americans suffer from diabetes. Roughly 1 million have Type I form of the disease, which generally occurs in childhood and involves the destruction of islet cells by the immune system. The rest have Type II, or adult-onset diabetes, which is tightly linked to obesity. In this disorder, the body's cells gradually become resistant to insulin, and, as with the Type I form, many patients must take injections of the hormone to avoid disabling or deadly consequences.

The liver and the pancreas have the same ancestry early in development. Yet while stem cells in the pancreas can become liver tissue, scientists haven't proven the reverse true.

The new study, which appears in the tomorrow's issue of the Proceedings of the National Academy of Sciences, addressed that question.

Lijun Yang and her colleagues at the University of Florida isolated and purified stem cells from rat livers, then treated them to remove a protein that prevents them from becoming other tissues.

By steeping them in glucose, Yang's group found that they could convert the liver stem cells into pancreatic cells. The cells assemble themselves into three-dimensional structures that resemble islet cells and secreted insulin when exposed to glucose. They also made other pancreatic hormones.

The researchers then transplanted clusters of the new cells into three diabetic mice, and saw that they could reverse the sugar problem in one of the animals. The key, Yang said, is giving the rodents enough of the grafted cells: 200 clusters in the case of the successful experiment vs. 20 in the ones that failed.

"This is the first time we show we can produce insulin-producing cells from a non-pancreas origin," Yang said. "Before, many studies produced them from pancreatic stem cells or embryonic stem cells, not from adult stem cells."

The next step, she said, is to determine whether the new islet cells function as well as their naturally occurring counterparts.

What To Do

For more on diabetes, try the American Diabetes Association or the Centers for Disease Control and Prevention.

SOURCES: Lijun Yang, M.D., assistant professor of pathology, University of Florida College of Medicine, Gainesville; Matt Petersen, director of diabetes information resources, American Diabetes Association, Alexandria, Va.; June 4, 2002, Proceedings of the National Academy of Sciences

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