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.
Nice post Paul. I would only add that it is not entirely clear that adult humans even neural stem cells, at least in meaningful numbers. These two recent papers certainly cast doubt on their existence in the adult human SVZ, the site of the most robust neurogenesis in rodents:
http://www.nature.com/nature/journal/v478/n7369/full/nature10487.html
http://www.cell.com/neuron/retrieve/pii/S0896627312003418
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Group this is interesting reading today. I am interested in how the Blood Brain Barrier Works, I once read about Dr. Brazzini, in Peru, who was injecting stem cells into the “circle of willis”, I remembered the name of this because of the movie star it was named after*, with positive results for his Parkinson Disease test patients, and somehow I think he had sidestepped the BBB.
http://www.jvir.org/article/S1051-0443(10)00087-4/abstract
* = 🙂
Thanks for the info, Paul. This goes along with a presentation I heard on work with human cord blood msc for AD. Evidence showed that memory could be created,but after a time it too would be lost. secondary stem cell treatments would allow for new memory to be created again, from a new start point again. etc. memory that was lost could not be recaptured.
I am very interested in this area of research myself and would sign on for this!. What I see is that the blood brain barrier is used as a catch all for lack of success and there has been minimal focus on the cytoskeleton or matrix and drilling down to how regulatory factors impact the brain and spinal cord ecosystem.. In other words if the intervention is not carefully prepared and targeted we are painting detailed areas with a broad brush. It is a little like putting new parts on a very old bike. I think if this was done accurately the memories etc would reform….they have attached donor hands years after the loss and it only takes the brain a short time t relearn the signals. Really cell and neuroscience people need to work together, I wish this could happen as both would be stronger.
A few days ago, a friend of mine told me one of his acquitances, while working on a PhD thesis on the role of serotonin in brain ischemia in a mouse model, discovered that after the initial injury, there is, in fact, an increase in proliferation of neuronal stem cells, but it’s short lived and they don’t engraft too well either.