October 29, 2020

The Niche

Knoepfler lab stem cell blog

Stem cells on the brain: why can’t the brain just fix itself?

p27 staining of mouse brain, cerebellum.
p27 staining of developing mouse brain, cerebellum.

Why doesn’t the brain fix itself using stem cells the way other organs do?

Earlier this week I was lecturing to students here at UC Davis on stem cells.

One of the points I raised was that most if not all of our organs have a compliment of stem cells that are there to maintain the organ and fix it when sick or injured.

I also pointed out that although there are stem cells in the brain, surprisingly there is little evidence that these endogenous stem cell have the ability to heal. If anything they seem to be present to regulate some nebulous activity related most likely to our sense of smell. It’s a puzzle.

So if almost every organ maintains an army of stem cells to fix itself, why not our brains?

This question is particularly important given the increasingly alarming realization in society of just how devastating brain injuries can be even those at the time of the injury do not seem that bad.

One answer to the question of why the adult brain apparently for the most part does not use its own endogenous stem cells to repair damage is that it is too risky. The brain is such a finely tuned computer that any kind of repair via new cell growth may be dangerous. Our thoughts and memories are probably embedded in the architecture of the brain itself and the way the cells of the brain interact. Therefore, any kind of repair by generating new brain cells risks serious problems such as incorrect wiring of circuitry and lost data (memories). In contrast, if your liver for example is damaged, your body can restore that function by generating a generic new chunk of liver. The brain doesn’t work that way. Each part is not necessarily interchangeable or replaceable. A new fresh clump of brain tissue generated after an injury may therefore do more harm than good.

If this model is correct it has enormous implications for stem cell-based regenerative medicine therapies for brain disorders because it means that simply generating new brain tissue is not good enough and could actually do harm. Thus, cellular therapies for brain pathologies may have higher risks than applying therapies based on the same concept of cellular replacement to other more homogeneous organs.

Another reason why the brain may not undergo stem cell-dependent repair is that keeping the population of brain stem cells at a minimum could reduce the risk of brain cancer, which in some cases is thought to arise from stem cells gone to the dark side. Similarly humans may pay a price for their huge brains in the form of higher risks of brain cancer.

This discussion highlights the importance of basic research for advancing translational and clinical therapies. If we lunge forward without a solid foundation of knowledge we increase risks and lower potential rewards.

A better understanding of brain development and stem cell function therein is essential in my opinion for crafting stem cell-based therapies for brain disorders. I have a passion for brain research (see article here also invoking the phrase “stem cells on the brain” but for the meaning of being preoccupied with the topic), but I think even more research is needed into how the brain grows, develops, and is maintained.

The same is almost certainly true of the heart, which has little if any endogenous regenerative capacity in humans. A regenerating heart risks arrhythmias or abnormal contraction and those same risks certainly apply to stem cell-based regenerative medicine for the heart.

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