Harvard scientists create insulin-producing cells in mice

By Carolyn Y. Johnson, Globe Staff

Harvard scientists have transformed mouse pancreas cells that aid digestion into the insulin-producing cells that are destroyed in childhood 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, does not involve embryonic stem cells and thereby avoids the ethical issues that arise from using such cells. It was also faster and more efficient than another method, in which scientists essentially spin back the clock, turning adult cells into embryonic-like stem cells that have the capacity to become any cell in the body.

The new technique, reported online today 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 stem cell researchers said it was an exciting demonstration that could spur scientists to think more broadly about converting cells of all types directly from one type into another.

"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.

Melton and colleagues systematically identified which genes were likely to trigger the switch by sorting through more than 1,000 genes that appeared to be involved in the development of the insulin-producing cells.

They found that by injecting viruses carrying three genes into mice, they flipped a switch in the pancreas, turning cobblestone-shaped pancreatic cells into smaller, spindle-shaped 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 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 less-than-1-percent success rate for the creation of embryonic-like cells -- called iPS cells -- from adult cells.

Formidable challenges lie ahead. The researchers did not cure diabetes in a mouse model of the disease, and 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.

"Basically, the bottom line is we have dozens to hundreds of ways that we can cure diabetes in mice. This is a beautiful piece of science with some very exciting results," said Dr. John Buse, president for medicine and science at the American Diabetes Association. "It's possible this kind of approach could possibly be successfully applied in humans, but it will takes many years."