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Insulin-producing cells grown in the lab offer hope to Type 1 diabetics
By Bijal P. Trivedi

Diabetics must test their blood sugar level and inject insulin about five times a day.

Researchers at the Joslin Diabetes Center in Boston have found a way to produce human beta-islet cells, pancreatic cells that supply the body with insulin, in the lab. Transplanting these lab-grown cells into people with Type 1 diabetes would release them from daily insulin injections, which are required to control their blood sugar level.

Only 3,000 pancreases, but more than two million needed

Until recently, two major problems prevented diabetics from receiving successful transplants of beta-islet cells from cadavers. The first is that most transplants are rejected by the immune system. The second is that beta-islet cells make up only three percent of the pancreas; therefore two donor organs are required to harvest enough beta cells for a single transplant.

In the United States there are more than one million Type 1 diabetics, with an additional 35,000 people diagnosed annually. But only about 3,000 pancreases become available each year, providing only enough cells for about 1,500 transplants.

Susan Bonner-Weir and her colleagues at Joslin are using cells from the adult pancreatic duct, which is normally discarded, to cultivate new insulin-producing cells. When some of these duct cells replicate, they revert to a more primitive type of cell that can serve as the precursor for any pancreatic cell, not just the duct cells from which they were derived. When these precursor cells are treated with a specific mixture of sugars and proteins, they can be directed to become beta-islet cells.

"It's a bit of alchemy. You take cells that are normally thrown out and turn them into gold," says Bonner-Weir, an author of the report that appeared in a recent issue of the Proceedings of the National Academy of Sciences.

It's going to be a few years before this will have a clinical impact

"This is a very important achievement from a basic science point of view, but the question is what's next," says R. Paul Robertson, of the University of Washington in Seattle. "Every diabetic in the world is going to want a transplant, so how are we going to grow enough islet cells? Susan Bonner-Weir's work addresses this issue," says Robertson.

The Boston team was able to grow 35,000 islet cells from the duct cell precursors of one pancreas, which falls far short of a normal healthy pancreas that contains about one million islet cells. "This is just a drop in the bucket. We can't make enough tissue for a transplant yet," says Bonner-Weir.

A person needs at least working 400,000 islet cells in order to stop daily insulin injections. "I think it's going to be a few years before the lab can increase the production of islet cells to the point where it will be clinically significant," says Robertson.

Type 1 diabetes, also known as juvenile or insulin-dependent diabetes, is characterized by abnormally high blood sugar levels caused by a lack of insulin-producing cells. Without insulin the body is unable to control the sugar level of the blood. High blood sugar levels can damage blood vessels and nerves, predisposing the patient to a higher risk of blindness, heart disease, stroke, nerve disease, and limb amputations.

Before human clinical trials can be considered, Bonner-Weir's immediate concern is to tweak procedures to increase the yield of islet cells. The team will then transplant the islet cells into diabetic mice to see whether the sugar levels are normalized.

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Bonner-Weir, S. et al. In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci USA 97, 7999-8004 (July 5, 2000).

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