Bystander Stem Cells Keep Original Neurons Humming

November 01, 2007

Stem cell transplants rescue memory problems in mice, but not in the way you might expect

A new study finds that neural stem cells may be able to save dying brain cells without transforming into new brain tissue, at least in rodents. Researchers from the University of California, Irvine, report that stem cells rejuvenated the learning and memory abilities of mice engineered to lose neurons in a way that simulated the aftermath of Alzheimer's disease, stroke and other brain injuries.

Researchers expect stem cells to transform into replacement tissue capable of replacing damaged cells. But in this case, the undifferentiated stem cells, harvested from 14-day-old mouse brains, did not simply replace neurons that had died off. Rather, the group speculates that the transplanted cells secreted protective neurotrophins, proteins that promote cell survival by keeping neurons from inducing apoptosis (programmed cell death). Instead, the once ill-fated neurons strengthened their interconnections and kept functioning.

"The primary implication here is that stem cells can help rescue memory deficits that are due to cell loss," says Frank LaFerla, a professor of neurobiology and behavior at U.C. Irvine and the senior author on a new study published in The Journal of Neuroscience. If the therapeutic benefit was indeed solely due to a neurotrophic factor, the door could be opened to using that protein alone as a drug to restore learning ability.

LaFerla's team genetically engineered mice to lose cells in their hippocampus, a region in the forebrain important for short-term memory formation. These mice were about twice as likely than unaltered rodents to fail a test of their ability to discern whether an object in a cage had been moved since their previous visit.

But when the mutant mice were injected with about 200,000 stem cells directly into their hippocampi and retested up to three months later, the injured animals performed up to par with their normal counterparts.

LaFerla's team found that in healthy mice that were similarly injected, the stem cells (which were marked with a green fluorescent dye) had spread throughout the brain. In the brains of the diseased mice, however, nearly all the cells congregated in the hippocampi. "Somehow, in the damaged region, there is some kind of signal that's telling the stem cells to stay local," LaFerla explains.

Curiously, the researchers discovered that only about five percent of the stem cells injected into the brain-addled mice matured into adult neurons. The surrounding neurons that were there all along, however, had sprouted a denser set of connections with other cells, presumably allowing for better transmission of information and recovery of function. "We think it's some neurotrophic factor being secreted by the [stem] cells," LaFerla says. If his group can identify it, he adds, they can answer the question: "Can that substance [alone] be provided to the brain and rescue the memory deficit?"

Eugene Redmond, a professor of psychiatry and surgery at Yale University School of Medicine notes the new work is "certainly well done. Their conclusion is similar to our study in Parkinsonian monkeys." He notes that in his study there was evidence of stem cells replacing lost neurons as well as other benefits conferred by the transplant.