SPEAK OUT! NewsBit
Repair of Neural Circuits in Stroke-damaged Mouse Brains
Donna O’Donnell Figurski
Basic research on the repair of damaged mouse brains has again produced a potential breakthrough for human therapy. The research may accelerate our ability to repair damaged human brains. A trial study for using this therapy in humans is now being designed.
I’ve already written about the extraordinary promise of cell therapy in eliminating or greatly reducing the effects of brain damage. Much of this promise has to do with the discovery of stem cells, which have the stunning ability to develop into virtually any kind of cell. (The previous NewsBit, however, showed that scientists found a way to cause a common cell type to develop into functional neurons directly without going through a stem-cell stage.) In a study earlier this year, scientists showed that stem cells surgically implanted into damaged human brains reduced the severity of symptoms. But in that study, the scientists were surprised to find that the added stem cells themselves did not become new neurons and form new circuits, but they somehow revved up the brain’s natural ability to heal itself.
Now scientists at the University of Southern California (USC) with help from scientists at the National Institutes of Health (NIH) have found a way to activate the implanted stem cells so they develop into neurons and become part of new neural circuits. The direct involvement of the added stem cells resulted in enhanced repair and a much greater loss of symptoms. One NIH scientist said, “If the therapy works in humans, it could markedly accelerate the recovery of these patients.”
Scientists had previously shown that an FDA (Food and Drug Administration)-approved reagent, the engineered protein 3K3A-APC, caused stem cells in culture to become neurons. The USC scientists wanted to see if 3K3A-APC would help the recovery of a brain-injured animal. The model used for brain damage was mice that were induced to have a stroke. The scientists implanted human stem cells and then treated the mice with 3K3A-APC or a placebo (mock-3K3A-APC). Mice that were treated with stem cells + 3K3A-APC did markedly better (some were almost normal) in tests of sensory perception and motor skills than did mice that were treated with stem cells + the placebo. Unlike the earlier study in which the added stem cells did not become neurons, these stem cells did become neurons if the mouse had been treated with 3K3A-APC.
The human stem cells not only became neurons, but they also formed normal connections with mouse neurons. Because the implanted cells were human, the scientists were able to use a human-specific toxin to kill only the implanted cells (the mouse cells were resistant to the toxin). When scientists killed the new neurons, the mice lost the signs of recovery. The scientists concluded that 3K3A-APC caused the cells to develop into neurons that then formed functional neural circuits, ultimately leading to recovery.
USC physician-scientist Berislav Zlokovic, M.D., Ph.D., who directed the research, said, “When you give these mice 3K3A-APC, it works much better than stem cells alone. We showed that 3K3A-APC helps the cells convert into neurons and make structural and functional connections with the host’s nervous system.” (Full story)
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