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Thursday, August 28, 2008

Going From one cell type to another without a stem cell

By Brandon Keim EmailAugust 27, 2008 | 12:57:26 PMCategories: Stem Cell Research

In an unprecedented flourish of genetic alchemy, scientists used a virus to coax one type of cell to become another, without the intermediate stem cell step.

The research, conducted with cells from the pancreas, could soon be used to treat people with diabetes -- but its long-term impacts could be even greater.

"This represents a parallel approach for how to make cells in regenerative medicine," said Douglas Melton, co-director of the Harvard Stem Cell Institute. "And now that it's shown that you can turn one of your cells into another, it makes you think of what other cells you'd like to convert."

Cell transformation has traditionally been accomplished by harvesting and reproducing stem cells. These are able to become other types of cells, raising the much-anticipated possibility of replacing disease-damaged and age-ravaged organs and tissues.

But stem cells are tricky. Using highly-versatile embryonic stem cells requires embryo destruction, a steady supply of human eggs and potentially dangerous hormone treatments for the women who produce those eggs. Adult stem cells, though ethically uncontroversial, are also hard to handle. Another technique, known as de-differentiation, can turn skin cells to stem cells -- but tends to introduce cancer-causing mutations.

Melton's team avoided stem cells, and their baggage, altogether by using a virus to tweak three developmental genes in pancreatic tissue cells in mice. Three days later, these became insulin-producing beta cells, and appear free from the complications that have frustrated stem cell researchers.

If the technique, described today in Nature, is replicated in humans, it could be used to treat insulin deficiencies in people with diabetes -- and that's just the start.

"Neurodegenerative diseases come to mind, as does cardiovascular disease," said Melton.

Arthur Caplan, a University of Pennsylvania bioethicist who wasn't involved in the study, called the findings a "breakthrough" for both diabetes and the field of regenerative medicine.

"It's a system that's easier to manipulate than getting a new stem cell to turn into something you want," he said. "The kind of work done here has the promise to go into clinical practice in a relatively short time."

Caveats remain, the foremost being the replication of the work in human tissue. The team managed to cause the transformation inside the mice, but in humans the transformation will need to be done in a tissue culture, producing cells than can be injected into recipients. And though Melton's team used a safe and well-characterized virus to induce the changes, the long-term safety of the new cells isn't proven.

Melton must also coax the transformed cells into forming groups known as islets, which produce the insulin used in humans.

"We've made a cell type, but we haven't yet made a whole tissue," said Melton. "But we're reasonably confident."

Melton's team is also seeing whether the same kind of cell transformation can be achieved in liver cells, or triggered by drugs.

Other researchers, he said, will apply the technique to other diseases.

"If you've got extra cells of one type and need another, why go all the way back to a stem cell?" said Melton.