CAN STEM CELLS BE USED TO REPAIR THE BRAIN ?

STEM CELLS TO REPAIR THE BRAIN

The central nervous system seems unable to regenerate cell loss: unlike what happens with skin, muscle, liver or bone cells, a destroyed neuron is not replaced. 

However, it has recently become known that the brain is one of those organs that contain stem cells, capable in theory of producing the various cell lines necessary to repair damaged organs and tissues. 

This discovery allows neurology to envisage exceptional progress and unexpected prospects for the development of cellular brain repair therapies. But for many questions remain …

STUDIES IN PERPETUAL EVOLUTION

Until about fifteen years ago, it was thought that the nervous system of mammals (and therefore humans …) was no longer able to form new nerve cells or neurons once embryonic development was complete. In other words, we considered that our brain was devoid of nerve stem cells, and that is why it could not regenerate or repair itself after an injury. 

An anthropocentric view even maintained that this lack of regeneration was the price to pay for evolution, postulating that our brain was so evolved that it had lost its ability to adapt and therefore repair. We now know that all of this is wrong and that our brains do contain nerve stem cells. We also know their faculties to form new neurons …

We must realize that the first observations describing these adult nerve stem cells had the effect of a real “bomb” in the community of scientists and that, as this is often the case during epistemological upheavals, it took about five years for the accumulation of observations and evidence all pointing in the same direction to persuade the most skeptical. 

In many ways, however, nerve stem cells are not comparable to hematopoietic stem cells …

STEM CELLS WITH RESTRICTED CAPACITIES ?

Different observations limit the comparison between nerve stem cells and their hematopoietic counterparts. First of all, nerve stem cells are present in very precise and restricted places of our brain since they have been located exclusively in the sub-ventricular zone and in the gyrus dentatus of the hippocampus. 

The fact that they are not present in all our brain induces important functional consequences. In fact, nerve stem cells give rise to neurons specifically intended for two structures: the olfactory bulb for cells in the sub-ventricular zone, and the CA3 region of the hippocampus for the gyrus dentatus . 

Furthermore, only the formation of small neurons could be observed. The role of these microneurons is limited to serving as intermediaries in nerve connections (which explains why they are also called “interneurons”). 

Thus, the neurons formed are not at all intended to replace the dopamine neurons affected in Parkinson’s disease or those with acetylcholine which disappear in Alzheimer’s disease. The same observation is essential concerning the large pyramidal neurons so important in voluntary motor skills and which are, for example, affected during thrombosis with hemiplegia or during other rarer diseases such as amyotrophic lateral sclerosis. 

So far, it has not been formally demonstrated that these cells are capable of forming oligodendrocytes, these non-neuronal cells that make myelin (or “sheath of nerve fibers”) and that are destroyed in sclerosis by plates. A final aspect differentiates nerve stem cells from hematopoietic stem cells: these are not ” recruitable “. 

This means that in the event of damage to the nervous system, they do not start to proliferate more significantly to reform the cells destroyed by the lesion. 

However, this is what happens in the bone marrow, for example, in the event of hemorrhage: we then observe a transiently increased production of red blood cells by the marrow following stimulation of hematopoietic stem cells.

MULTIPOTENTIALITY AND SELF-RENEWAL

Under these conditions, why are these cells called “nerve stem cells”? In fact, the situation which has just been described corresponds to the conditions in vivo. However, if nerve stem cells taken from adults by different techniques are cultured, it is observed that these are capable of actively proliferating for very long periods of time. 

They are said to be self-renewing. Furthermore, if allowed to differentiate, c ‘ is to -dire become more “mature” is observed in these culture conditions, the appearance of different cell types: neurons, oligodendrocytes and astrocytes (the third type cell of our brain and whose many and varied roles facilitate the work of neurons) . 

They are therefore also multipotential . The multipotentiality and self-renewal are the classical properties of tissue or somatic stem cells, we can adopt the term “stem cells nerve” on the basis of these in vitro observations. Identifying the potentials of nerve stem cells has dramatically changed the way we think about how the brain works, as well as how we treat various neurological diseases. 

A culture of stem cells from adult mice was carried out and the cells were then placed under differentiation conditions.
Immunofluorescent labeling of the cells was carried out so as to be able to distinguish them specifically. Thus the astrocytes are marked in green, the oligodendrocytes are marked in blue and a neuron marked in red is observed, of which a long axonal extension is perfectly well followed (white arrows).

We could understand that our brain is not as “monolithic” as we thought: it is indeed capable of changing during the life of the individual and of integrating new neurons in a fiber circuitry nervous and connections (we speak of synapses) already complex. 

A question does not fail to arise in the continuity of this observation: what is the use of the new neurons that we produce each day of our life (we have indeed calculated that each day, we are, for example, capable of forming a new neuron for two thousand neurons existing in the gyrus dentatus …). Several hypotheses have been put forward. 

The most attractive of them is to think that these “neo-neurons” are involved in the processes of learning and memorization. However, nothing formal has been demonstrated on this subject. 

The only objective consideration which has been made possible is that adult neurogenesis is slowed down in the event of depression, and that it is favored by various circumstances (such as running for example), without it being understood why. one and the other case …

POSSIBLE THERAPEUTIC REVOLUTIONS

The upheavals that have marked neurology over the past fifteen years suggest real therapeutic “revolutions”. And it is a cautious, but resolute optimism that guides researchers today … A very first objective to reach before developing new therapies is to understand why nerve stem cells cannot be recruited . 

We know that this incapacity is not linked to their intrinsic nature since it has been observed that they actively proliferate in culture and differentiate in many types of neurons or glial cells (astrocytes and oligodendrocytes). It is therefore that their cerebral environment is not “favorable”.

In other words, even in the event of lesions, no signal seems capable of activating them. It is therefore necessary to better understand their biology to eventually consider ways to recruit them by an adequate signal. In addition, if our brain is able to “integrate” itself neo-neurons, the transplantation of nerve cells should logically be possible. 

The possibilities of cell therapy, that is to say grafting of cell suspensions intended to replace dead or damaged cells in the event of injury, are therefore now considered in a much more concrete manner. As is often the case in scientific research, we find that a discovery brings new and many questions. 

It can also give rise to many therapeutic hopes for diseases for which sometimes, even at the dawn of the 21st century, we are still destitute. 

However, a better knowledge of the biology of these cells is absolutely necessary to answer these questions and one day hope for new treatments. And in this last area in particular, we must beware of any haste that could lead to causing the patient more serious problems than the disease that we wanted to treat at the start. 

The old aphorism dear to many careful doctors, primum non nocere (first do no harm) is needed here more than ever.

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