Wednesday, July 8, 2015

Stem cells: this post gets weird at the end

A friend recently asked me whether stem cells could be grafted into a brain to repair damage from a stroke.  I didn't know the answer, so I went looking for it.

This reminded me of an episode of South Park from a long time ago.  In it, Cartman lobbies for the use of stem cells in order to save Kenny's life, only to reveal that all he wanted all along was to use them to clone a Shakey's Pizzaria.

The reason I bring this up is because it harkens back to the first layman explanation of stem cells I ever heard back in 2001.  The explanation given was that stem cells turn into whatever they're around.  For many, this is still the extent of what is known.

If this is true, stroke treatments make a lot of sense.  To my knowledge, there are no real treatments for a stroke.  A whole bunch of brain cells die and you lose the function of whatever they were needed for.  Sometimes you can go through rehab to find new ways to rely on other parts of the brain, but the damaged part of your brain is simply dead.

So does it work?  If we inject stem cells into the damaged region, will they just fill in the space and repair everything?

SORT OF.

You see, grafted stem cells have been shown to provide benefits.  However, the benefits are not miraculous.  The cells do not, as Cartman believed, just replicate whatever they're around.  If you graft in neural stem cells, you don't just get a bloom of fresh healthy neurons.  In fact, many of the biggest improvements are actually the result of implants of mesenchymal stem cells.  These are not the progenitors of brain tissue, but rather of cartilage, bone, and connective tissue.  Why?  For reasons which are at the same time disappointing and extremely promising.

The reason is that the stem cells don't replicate their surroundings as magically as we might hope. Contrary to hype, they don’t naturally proliferate into all damaged spaces and replace the exact cells which were lost as though by magic.  They act based on a wide range of cues from inside of and outside of the cells, and the surrounding environment of a brain lesion isn't really conducive the cells development and growth.

But if we stop hoping that the cells will just magically reverse damage we discover that healthy cells can do other incredible things.  To understand this, try to understand that a stroke is not over when it ends.  It leaves behind damage that continues to harm the brain.  The lingering damaged tissue is garbage impeding the function of the healthy area around it and increasing the likelihood of future strokes.  Adding healthy cells -- especially mesenchymal cells -- appears to nurse the wound.  It reduces inflammation.  It expresses growth factors to encourage regrowth or mobilize the body to remove the waste.  It suppresses effects of the immune system which might attack the body in error.  And it appears to encourage the growth of new blood vessels to nourish the region with the essential oxygen that it needs more than ever following a stroke.

This seems to me akin to picking the victim of a car accident off of the pavement, placing them in a hospital bed, and supplying them with plenty of fluids. We haven’t replaced lost blood, we haven’t set broken bones, we haven’t mended wounds. We’ve just given them a healthy environment in which to limit further damage, and that alone has shown marked benefits.

The key is, I no longer think of stem cells as a means of making more cells in the body.  I now think of them primarily as a tool through which we can affect a malfunctioning body part.  Lack of blood vessels?  Low insulin response?  Insufficient dopamine production?  We have a cell for that.

What I find most fascinating is that the treatments described use an approach that will likely seem very primitive in the next century.  Instead of expecting the cells to just replace something that is missing we can now design biological machinery to do complex tasks within the body.  If we find that the cells are providing a growth factor which promotes neural regeneration we can design modified cells to do precisely that, perhaps in response to a drug we can provide to adjust their output. 

If we take this concept even further we realize that we do not need to merely strive to make cells as close as possible to natural ones.  We can invent new cell types.  We could make a cell that senses magnetic fields and provide humans with the internal compass that whales and birds enjoy.  We could make color-changing cells to embed in skin like organic, changing tattoos.  We could design new optic cells which see in colors outside of the visible spectrum.  It's fortunate that these kind of developments are a long way off, because they raise huge ethical questions.  The point is, we're on the edge of a whole new era of biology and medicine.  I don't want to overstate it, but imagine the days before pharmacology.  Now imagine after.  That's what we're looking at.

The review I liked:

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