August 28, 2008

Scientists Reprogram Adult Cells

Scientists have successfully changed the identity of one type of cell into another in living mice, potentially paving the way for new developments in the growth of replacement tissues used to treat a broad spectrum of diseases.

Researchers were able to transform ordinary pancreas cells into a rare type that creates insulin, which may provide future help for those who suffer from diabetes.

What's more, scientists say this development could reach much further than possible treatments for diabetes. It could lead to treatments like growing new heart cells after a heart attack or nerve cells to treat disorders like ALS, also known as Lou Gehrig's disease.

The work is "a major leap" in reprogramming cells from one kind to another, said one expert not involved in the research, John Gearhart of the University of Pennsylvania.

That's because the feat was performed in living mice rather than a lab dish, the process was efficient and it was achieved directly without going through a middleman like embryonic stem cells, he said.

Although this is a huge scientific step, Douglas Melton, co-director of the Harvard Stem Cell Institute and a researcher with the Howard Hughes Medical Institute, wrote in the journal Nature that the approach is not ready for people.

Scientists have long hoped to find a way to reprogram a patient's cells to produce new ones. Research with stem cells, and similar entities called iPS cells that were announced last year, has aimed to achieve this in a two-step process.

The first step results in a primitive and highly versatile cell. This intermediary is then guided to mature into whatever cell type scientists want. That guiding process has proven difficult to do efficiently, especially for creating insulin-producing cells, Gearhart noted.

In contrast, the new method holds the promise of going directly from one mature cell type to another. It's like a scientist becoming a lawyer without having to go back to kindergarten and grow up again, Melton says.

This means that scientists may one day be able to replace dead cells by reprogramming nearby cells.

Researchers used poison to destroy beta cells in mice, which made them develop diabetes.

The mice were then injected with viruses that slipped into enzyme-producing cells.

Within three days of the injection, new insulin-secreting cells began to appear. One week later, more than a fifth of the virally infected cells started making insulin.

Scientists found evidence that the newcomers were converts from mature enzyme-making cells. They identified the new cells as beta cells by their detailed appearance and behavior, and Melton said they've continued functioning for months.

The new cells didn't fully replenish the insulin supply, but maybe there were too few of them, or they were hampered by not forming clusters like ordinary beta cells do, researchers said.

The work brings "more excitement to the idea of using reprogramming as a way to treat diabetes," said researcher Mark Kay of Stanford University, who is studying the approach with liver cells.

Melton, who began his diabetes research in 1993 when his infant son was diagnosed with the illness, said he's obsessed with trying to find a new treatment or cure for Type 1 diabetes, in which beta cells are destroyed.

"I wake up every day thinking about how to make beta cells," he said.


Image 2: In this immunofluorescent image of an adult mouse pancreas, exocrine cells into which three transcription factors have been inserted are displayed in green. The red areas in the image are insulin. The blue streaks are blood vessels, which are remodeled by and lie close to the new, insulin-producing beta cells.


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