Researchers Report Advances in Cell Conversion Technique

(From the New York Times)

Biologists at Harvard have converted cells from a mouse’s pancreas into the insulin-producing cells that are destroyed in diabetes, suggesting that the natural barriers between the body’s cell types may not be as immutable as supposed.

This and other recent experiments raise the possibility that a patient’s healthy cells might be transformed into the type lost to a disease far more simply and cheaply than in the cumbersome proposals involving stem cells.

The new field depends on capturing master proteins called transcription factors that control which sets of genes are active in a cell and thus what properties the cell will possess. Each type of cell is thought to have a special set of transcription factors.

Last year a Japanese biologist, Shinya Yamanaka, showed that by inserting four transcription factors into an adult cell he could return it to its embryonic state.

In a variation of this technique, a team led by Qiao Zhou and Douglas A. Melton at Harvard has now identified three transcription factors active in the insulin-producing beta cells of the pancreas.

They hitched the genes for these three factors onto a virus that infects another type of pancreatic cell, known as an exocrine cell. In mice made diabetic by a drug that kills beta cells, the transformed exocrine cells generated insulin, allowing the mice to enjoy “a significant and long-lasting improvement” in their diabetic state, the researchers are reporting Thursday in the journal Nature. Although many steps remain before the technique could be considered for human use.

Besides producing insulin, the transformed exocrine cells looked like beta cells and ceased making proteins typical of exocrine cells. But they did not organize themselves into the pancreatic structures known as islets where beta cells usually cluster. The researchers claim only to have made “cells that closely resemble beta cells.”

Even so, Robert Blelloch, a cell biologist at the University of California, San Francisco, said, the Harvard experiment was “a very nice story — it’s pretty impressive that you can make such a switch just by adding three factors to a quite different cell type.”

Last month Patrick Seale and Bruce Spiegelman of the Dana-Farber Cancer Institute in Boston showed how with a single transcription factor they could make white fat cells generate brown fat cells, a very different type of cell. The Harvard work “is not occurring in a vacuum, but it’s a very important piece of work,” Dr. Blelloch said.