Making brain stem cells act more like salmon than bloodhounds

Like salmon swimming against a river current, brain stem cells can travel against their normal migration stream with the help of electrical stimuli, so says CIRM-funded research published this week in Stem Cell Reports. The research, carried out by a team of UC Davis scientists, could one day provide a means for guiding brain stem cells, or neural stem cells (NSCs), to sites of disease or injury in the brain.

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Human neural stem cells (green) guided by electrical stimulation migrated to and colonized the subventricular zone of rats’ brains. This image was taken three weeks after stimulation. Image: Jun-Feng Feng/UC DAVIS, Sacramento and Ren Ji Hospital, Shanghai.

NSCs are a key ingredient in the development of therapies that aim to repair damaged areas of the brain. Given the incredibly intricate structure of nerve connections, targeting these stem cells to their intended location is a big challenge for therapy development. One obstacle is mobility. Although resident NSCs can travel long distances within the brain, the navigation abilities of transplanted NSCs gets disrupted and becomes very limited.

In earlier work, the research team had shown that electrical currents could nudge NSCs to move in a petri dish (watch team lead Dr. Min Zhao describe this earlier work in the 30 second video below) so they wanted to see if this technique was possible within the brains of living rats. By nature, NSCs are more like bloodhounds than salmon, moving from one location to another by sensing an increasing gradient of chemicals within the brain. In this study, the researchers transplanted human NSCs in the middle of such a such gradient, called the rostral migration stream, that normally guides the cells to the olfactory bulb, the area responsible for our sense of smell.

Electrodes were implanted into the brains of the rats and an electrical current flowing in the opposite direction of the rostral migration stream was applied. This stimulus caused the NSCs to march in the direction of the electrical current. Even at three and four weeks after the stimulation, the altered movement of the NSCs continued. And there was indication that the cells were specializing into various types of brain cells, an important observation for any cell therapy meant to replace diseased cells.

The Scientist interviewed Dr. Alan Trounson, of the Hudson Institute of Australia, who was not involved in study, to get his take on the results:

“This is the first study I’ve seen where stimulation is done with electrodes in the brain and has been convincing about changing the natural flow of cells so they move in the opposite direction. The technique has strong possibilities for applications because the team has shown you can move cells, and you could potentially move them into seriously affected brain areas.”

Though it’s an intriguing proof-of-concept, much works remains to show this technique is plausible in the clinic. Toward that goal, the team has plans to repeat the studies in primates using a less invasive method that transmits the electrical signals through the skull.

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