Gain without pain. Genetically altered neural stem cells (green) repair damaged nerve fibers (red) in paralyzed rats without the abnormal pain caused by unaltered stem cells.

Stem Cell Side Effect

Some of the benefits of stem cells may come with painful side effects, new research suggests. Rats treated with stem cells for spinal cord injuries seem to experience intense pain from even a gentle touch. On the bright side, the team reports that genetically modifying the cells before injecting them may alleviate the problem.

Spinal cord injuries disrupt the communication link between the brain and the muscles that move the body, resulting in irreversible paralysis. But in 1999, researchers raised hopes of a treatment when they restored some movement in injured rats with injections of stem cells--immature cells that can turn into various cell types. (ScienceNOW, 30 November, 1999 ). Since then, many teams have been trying to improve on the technique.

When Christoph Hofstetter and colleagues at the Karolinska Institute in Stockholm, Sweden recently injected adult neural stem cells into rats with hind limbs partially paralyzed by spinal cord injuries, the animals showed improved mobility in their hind limbs after about 5 weeks. But the team also noticed that the rats' forepaws had become extremely sensitive. A light touch or moderate warmth or cold made the rats extremely agitated.

After examining the rats' spinal cords, the team thinks they've figured out why. Nearly all of the stem cells turned into astrocytes, a type of support cell that cranks out compounds that encourage neurons to grow new branches. The neurons that transmit pain appear to be sensitive to these "grow" signals, Hofstetter says, which could explain why the rats have abnormal pain responses. The team then added a gene that suppresses astrocyte formation to the stem cells so that more of them turned into oligodendrocytes, another type of support cell that repairs the insulation on damaged nerve fibers. Rats treated with these cells showed even greater recovery of movement--with little, if any, abnormal pain, the team reports in the March issue of Nature Neuroscience.

The findings suggest that controlling the fate of stem cells will be crucial for maximizing the benefits of future therapies and avoiding serious side effects, says Clive Svendsen, a neuroscientist at the University of Wisconsin, Madison. However, Geoffrey Raisman of University College London questions the study's clinical relevance. "The overwhelming cause of disability in human spinal cord injuries is the disconnection of nerve fibers," he says. "There's no indication that any of the procedures used here repair disconnected nerve fibers."

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