Mouse-tail cells converted into brain cells at Stanford

Skin cells from the tails of mice were turned into neurons able to form connections crucial to brain function, a study said. The Stanford University scientists who performed the feat said it should work with human tissue.

The research, published Wednesday in the journal Nature, is the latest demonstration that cells' basic functions can be transformed by inserting or turning on the right genes in their DNA. In this case, that was accomplished without first turning the skin cells into the equivalent of embryonic stem cells before they were changed into different kinds of body cells.

The work provides a more efficient way to make neurons from the skin of people with Alzheimer's and Parkinson's diseases than a method developed four years ago by Shinya Yamanaka of Kyoto University in Japan. Yamanaka's breakthrough showed that skin cells from mice or humans could be made into stem cells and manipulated again to become any cell in the body.

The paper "might be a landmark," said Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Institute in La Jolla, Calif. "There's a long history of failure in this field. Researchers tried for 30 years to convert a common cell type into neurons. People published papers, but no one ever made a real neuron."

The research was led by Marius Wernig, an assistant professor of pathology at Stanford's Institute for Stem Cell Biology and Regenerative Medicine. Wernig, 35, and his colleagues identified 19 genes that are active in neurons and inserted them into skin cells taken from the tails of young mice. The team used a type of virus known as a lentivirus to carry the genes into the skin cells.

After a month, a few of the skin cells showed signs of having turned into brain cells. The team then used a trial-and-error process to identify three genes from among the 19 that could do the job on their own.

Using the three, Wernig's team found that in just two weeks, 20 percent of the skin cells had changed into neurons.

"That means reprogramming doesn't only go backward but can occur in any direction," Wernig said in a telephone interview Friday. "If you extrapolate from this, you could probably turn any cell in your body into any other cell if you just know the right factors. A year ago, I would not really have believed this was possible."

Wernig and his colleagues are trying to do the same thing with human cells and Stanford has applied for a patent on the process. If it works in human cells, researchers could use the method to turn skin cells from a patient with Parkinson's or Alzheimer's disease, for example, into neurons with the genetic defects that cause the condition.

This would allow researchers to study the workings of the disease and to test drugs that might treat it, Wernig said.

Two years ago, Douglas Melton, a researcher at Harvard University's Stem Cell Institute who focuses on diabetes, showed that one cell in the pancreas could be turned into another without first reverting to a primitive, embryolike cell. Melton said the Stanford work was a major advance because it starts with cells that can be easily obtained from a person.

"If you wanted to make more cells for yourself, the ones you'd be willing to give up are fat, skin, hair, blood, not brain cells," Melton said.

The process also takes a more direct route to changing the function of cells than Yamanaka's method, Melton said.

"Instead of trying to turn them back into pluripotent stem cells and then make those into differentiated cells, he's short-circuiting that process and saying let's go right from one readily available cell to another cell of interest," Melton said.