Who’s the boss of the brain? How stem cells repair damage

Tony Wyss-Coray

In addition to their usual job of creating new cells, stem cells in the brain turn out to be excellent managers. That’s according to CIRM-funded researchers at Stanford University, who have recently published a paper describing how stem cells in the brain control the behavior of other cells.

The work could help explain why stem cell transplants appear to improve brain function even when they don’t form connections with other brain cells.

The paper itself, which was published in the journal Nature Neuroscience, has a lot of talk about cells in the brain communicating via a variety of acronym-laden molecules. What it all comes down to is this: stem cells in the brain and the cells they create (with the cumbersome name “neural progenitor cells) are the managers of a vast army of other cells. Damage the stem cells and you disrupt how those other cells behave.

Bruce Goldman at Stanford University described the work in superhero terms in a press release. Imagine a group of cells in the brain whose job it is to swoop around cleaning up damage (these cells are called microglia). Most of the time, they are like Clark Kent, puny and inactive. But when the neural progenitor cells give the signal they puff up and go on the attack.

One thought has been that disorders such as Alzheimer’s and Parkinson’s as well as damage after stroke might result, in part, when those superhero cells aren’t properly called to action. This could explain why transplanting stem cells into brains of people with those diseases might help improve symptoms. It’s like dropping a good manager into a disorganized office. Where once other cells meandered about without purpose, the neural progenitor cells instill order and put those microglia to work.

Goldman also wrote an entry on Stanford’s blog about the work, which contains possibly the clearest description of neural stem cells and their progeny that I’ve read. He writes:

Neural stem cells get plenty of good press, and understandably so. They’re the matriarchal cells of the brain, from which spring all except one type of cell populating our most highly regarded (at least by itself) organ. They can remain in their primordial state for decades, languidly dividing just enough to replace their own numbers. Alternatively, they can spawn daughter cells that depart from the primordial state.

It’s the matriarchs’ daughters – so-called neural progenitor cells – that embark on committed differentiation pathways giving rise to nerve cells and other key brain cells. Given that lofty ambition, it’s not surprising that neural progenitor cells divide much more rapidly than their parents do, outnumbering neural stem cells probably by 1,000 to 1 or more.

It turns out that neural progenitors can do more than breed. They’re excellent managers, too.

This work was funded by a CIRM Basic Biology awards, which are intended to fund research that better explains how stem cells function. This study is a great example of why those awards are so valuable. It’s hard to convince the Food and Drug Administration to allow you to test stem cells in people if you can’t also explain how those cells are working. This research begins to get at why transplanted stem cells appear to work, and could help other researchers move closer to testing their therapies in people.

CIRM funding: Tony Wyss-Coray (RB2-01637)


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