Famous for their capacity to turn into any type of nerve cell, adult neural stem cells can also serve as anti-inflammation police in the brain, researchers have found. When injected into mice with an inflammatory brain disorder similar to multiple sclerosis, these versatile cells home in on and destroy certain bloodborne inflammatory immune cells.
In addition to serving as a source of replacement cells for damaged neurons, the stem cells act as anti-inflammatory drugs that target sites of nerve damage, says Stefano Pluchino of San Raffaele Scientific Institute in Milan, Italy.
Even more important, the injected mouse stem cells survived repeated inflammatory episodes characteristic of chronic diseases such as multiple sclerosis, report Pluchino, team leader Gianvito Martino, and their coworkers in the July 14 Nature. The stem cells escape damage by remaining undifferentiated and therefore less vulnerable to immune system attack, the researchers suggest.
The findings add to a growing body of evidence that adult neural stem cells can serve protective as well as restorative functions in the brain, comments Evan Snyder of the Burnham Institute in La Jolla, Calif.
Snyder and his colleagues had previously shown that neural stem cells are drawn to brain tumors and areas of a brain injured by stroke. Once there, Snyder’s team found, the stem cells diminish inflammation, often a major cause of tissue damage. Some of the cells also differentiate into neurons, thereby replacing ones killed by disease.
The cells act as both firefighters and construction workers, says Snyder. “They go to where the fire is, they put out the fire, and then they start trying to rebuild the area.”
The new study by Pluchino and his colleagues “provides a molecular mechanism that starts accounting for some of these observations,” Snyder says.
In multiple sclerosis, as with other autoimmune disorders, the patient’s own immune cells attack the body and cause repeated episodes of damaging inflammation. In the mice, induced to have a disorder similar to multiple sclerosis, injected neural stem cells persisted for more than 3-and-a-half months and 5 to 7 inflammatory episodes.
The stem cells carried molecules that are attracted to molecules found in inflamed areas of the central nervous system. The cells accumulated in blood vessel walls near these areas and appeared to induce suicide in inflammatory immune cells. Though most of the stem cells remained undifferentiated, about 5 to 7 percent maintained their ability to differentiate into nerve cells and to potentially rebuild damaged brain areas.
“The fact that the adult neural-precursor cells can survive and grow in the central nervous system during a chronic inflammatory disease is really important,” says Judith Greer of the University of Queensland in Australia. If the cells succumbed to inflammatory episodes after the initial injection, “there would be no point even trying to use them therapeutically in humans,” she adds.
In addition to multiple sclerosis, adult neural stem cells could eventually treat a wide variety of inflammatory disorders, such as stroke, brain tumors, Parkinson’s disease, and Lou Gehrig’s disease, Snyder speculates. But Pluchino says that clinical trials of anti-inflammatory stem cell therapies in people are at least 4 to 5 years away.