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New technique finds a faster way to change one cell type into another

By Carolyn Y. Johnson
Globe Staff / August 28, 2008
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CAMBRIDGE - Harvard researchers have transformed one type of pancreas cell in living mice into another - the insulin- producing cells that are destroyed in type 1 diabetes - potentially giving stem cell scientists a powerful new way to one day grow replacement tissues for patients.

The technique, which the researchers said improved diabetic symptoms in the mice, is faster than another pioneering method, in which scientists turn mature adult cells into embryonic-like stem cells that have the capacity to become any cell in the body.

The new technique, reported online yesterday in the journal Nature, is years away from having benefits for diabetic patients, according to Douglas Melton, a co-author and co-director of the Harvard Stem Cell Institute. But other researchers said it was an exciting demonstration that could spur scientists to think more broadly about converting mature cells of all types into another type in the same organ - taking, for example, a bit of heart tissue and transforming it into cardiac muscle.

"The message for those of us working in other organs . . . is it opens up the possibility of directly forming those different cells, in our case, heart muscle cells," said Dr. Kenneth Chien, a colleague of Melton's and director of the Cardiovascular Research Center at Massachusetts General Hospital.

The work is the latest in a series of advances in stem cell research that have helped shift the focus away from obtaining stem cells from embryos, a practice that is controversial because it involves the destruction of embryos. Two years ago, Japanese scientists altered stem cell science with their report that it was possible to reprogram a cell, turning it into an embryonic-like stem cell called an iPS cell, which was capable of turning into any cell in the human body. Melton's team has shown it's possible to skip that stem cell-like state altogether.

Melton and colleagues painstakingly identified which genes were likely to trigger the cell switch by sorting through more than 1,000 genes and winnowing them down to ones that played a role in the development of insulin-producing cells. They found that by injecting viruses carrying three genes into mice, they could turn the pancreatic cells into beta cells that produce insulin.

"It's the first paper that did sort of a systematic approach to finding the factors that could do reprogramming - as opposed to guessing," said Dr. Markus Grompe, director of the Oregon Stem Cell Center at Oregon Health and Science University. He was not involved in the Harvard study.

In the mice, a fifth of the cells made the jump from one cell type to another, much higher than the current success rate of less than 1 percent for the creation of iPS cells from adult cells.

Diabetes researchers have long been trying to create the beta cells that die in type 1 diabetes, which typically starts in childhood and affects as many as 3 million Americans. Without the cells, which produce insulin that regulates the level of sugar in their bloodstream, patients are forced to constantly monitor their blood sugar levels and take insulin by injection or pump.

The work represents a step forward, but researchers have more work to do as they try to turn their finding into a cure for the disease. They have yet to achieve the same transformation in human cells. Type 1 diabetes comes with the additional obstacle that even if the correct cells are created in people, the patients' immune system will destroy them.

Carolyn Y. Johnson can be reached at cjohnson@globe.com.

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