Brain cells, like kids, can be led astray if they run with the wrong crowd. Neural stem cells, normally destined to turn into neurons and other brain cells, instead become muscle when they are put in contact with muscle cells, researchers now report. The results provide more clues about how cells choose a particular fate and may guide efforts to use stem cells to treat certain diseases.

Based on close observation of animal development, scientists had assumed that a cell's fate is assigned early in life--and is irreversible. But a slew of results in the past 2 years have all but erased that idea. In previous experiments, neural stem cells have been able to integrate into developing embryos and turn into many different types of cells, including heart and liver (ScienceNOW, 1 June) and even blood (21 January 1999).

Now, Angelo Vescovi and Giulio Cossu of the Stem Cell Research Institute in Milan, Italy, and their colleagues have pushed neural stem cells in still another new direction. In the first phase of their work, they exposed neural stem cells taken from the brains of mice to immature skeletal muscle cells in a lab dish. Within days, the neural stem cells began to make proteins typical of muscle cells, and even joined with the muscle cells to form myotubes, tubes of fused cells that make up the bulk of living muscle. Then to see whether something similar occurs in living animals, the team injected neural stem cells into the damaged muscles of mice. Two weeks later, the researchers found the brain-derived cells in the regenerating muscle tissue--suggesting that neural stem cell lines might be candidates for treating certain muscle diseases. Neural stem cell lines derived from human fetal brain tissue achieved the same feats, the researchers report in the October issue of Nature Neuroscience.

It seems, however, that the stem cells require a bit of cellular hand-holding to adopt their new fate. When the team kept the neural cells and muscle cells separated by a porous membrane, the neural stem cells showed no sign of becoming muscle. That suggests, says Vescovi, that cell-to-cell contacts play a crucial role in determining cell type.

The work shows "quite convincingly" that the brain cells can become normal-looking muscle, says developmental neuroscientist Derek van der Kooy of the University of Toronto. The next step, says Ron McKay, a stem cell biologist at the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, is to determine what allows the transformation to take place.

--GRETCHEN VOGEL

Related sites
Stem cell information from the National Institutes of Health