Insulin Cells Made Without Stem Cells

Aug. 27, 2008 -- Cells needed to treat disease can be made directly from abundant, easy to reach fat, blood, or muscle cells without the need for stem cells, Harvard researchers suggest.

One of last year's scientific breakthroughs was the announcement that adult cells can be reprogrammed into stem cells. Those stem cells can then become virtually any cell in the body.

Now researchers led by Douglas Melton, PhD, co-director of the Harvard Stem Cell Institute, find it's possible to skip the stem-cell step and turn adult cells directly into other kinds of cells.

In living mice, Melton's team was able to change normal pancreas cells into insulin-producing cells closely resembling the insulin-making beta cells that are lost in people with diabetes. These cells made enough insulin to lower the blood sugar of diabetic mice and to improve their glucose tolerance.

Amazingly, the transformation of the adult cells required delivery of just three chemical messenger molecules. These messengers were coded in the DNA of harmless, genetically engineered viruses injected into the mouse pancreas.

"In principle, patient-specific cell therapies could be achieved more directly by reprogramming abundant and easily accessible patient-specific human cells," Melton and colleagues conclude. Their report appears in the Aug. 27 online issue of Nature.

To find the three chemical messengers that reprogrammed the adult cells, the researchers focused on transcription factors, a class of genes that tells embryonic stem cells what kinds of adult cells to become. They then screened more than 1,100 transcription factors to find those that acted on the embryonic pancreas.

Although the Melton team created insulin-making cells in this experiment, similar techniques could potentially create any kind of functional cell.

Yet it's no accident the team created insulin-making cells in their first project. When Melton's son was diagnosed with type 1 diabetes in 1993, he directed his research efforts toward finding a cure for the disease. Melton's daughter also has diabetes.

While the new discovery holds great promise, there's still a long way to go. The new insulin-making cells don't organize into the efficient islets that promote normal beta-cell function, so they don't make as much insulin or respond as well to blood glucose levels as normal beta cells.

"Strategies that promote aggregation of the induced beta-cells should help to restore full glucose responsiveness," Melton and colleagues suggest.