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See Inside February/March 2008

Stem Cells for Memory

New synapses repair recall after a stem cell injection

Stem cells have long been heralded as a potential treatment for a range of brain ailments, but research has so far focused on movement disorders such as Parkinson’s disease. Now a new animal study shows that the immature cells could also help with cognitive impairments. Frank M. LaFerla of the University of California, Irvine, and his colleagues showed that neural stem cells can reverse memory loss.

The team manipulated the genome of mice such that they could initiate neuron death in the hippocampus by turning on specific genes. Mice whose brains were injured with this method showed significant memory impairment on place-recognition tests. After receiving an injection of neural stem cells from young mice, however, they performed as well as healthy mice did.

When the researchers tracked the stem cells in the mice’s brains, they saw that only about 5 percent of them actually developed into neurons, suggesting the cells did not rescue memory by replacing dead neurons, LaFerla says. Instead mice injected with stem cells developed a far greater number of synapses, or connections between neurons, at the damaged site than control mice did. LaFerla thinks that neurotrophins—biochemical compounds secreted by the injected stem cells—most likely were responsible for the effect. This finding could open the door for drug treatments based on these compounds. “Such a treatment would be much less risky than injecting actual cells,” he says, adding that transplanted stem cells could potentially develop into tumors.

That risk is currently a hurdle in many stem cell therapies, says Curt Freed of the University of Colorado Health Sciences Center in Denver. For example, animal studies have shown that neurons derived in the lab from human embryonic stem cells improve Parkinson’s symptoms; however, any residual stem cells associated with those neurons could form masses of unwanted cells. But scientists are making progress in refining these therapies, and the first ever trial of fetal stem cells injected directly into the brain is currently under way in children with Batten disease, a rare and fatal illness of the nervous system.

Freed expects transplants of neurons derived from embryonic stem cells to enter the clinical arena soon as well. “I think Parkinson’s will be the first disease in which these cells are used, and I would say that that’s likely to happen as early as two years from now.”

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