07 September 2010

We will grow neurons according to the customer's sketches

Surrogate neurons will cure paralysis and Stephen HawkingAlla Solodova, Infox.ru
Neuroscientists managed to overcome an obstacle that prevented many scientific groups from growing motor neurons of a certain type from stem cells.

In order to succeed, the scientists decided not to add extra to the system, but to select a part of the necessary one.

During embryogenesis, the only universal (totipotent) stem cell gradually loses its uniqueness. Subsequent generations of the omnipotent zygote are becoming more and more specific – precursors appear that give rise to a certain "genus" of cells. And even in one cellular "family", "relatives" are not similar to each other.

Scientists do not yet know how to grow therapeutically necessary cells in a "laboratory incubator", since the subtleties of the molecular background of "intraspecific diversity" remain unexplored. And for each cell, these very subtleties are unique in due measure – by changing one of the conditions (or active substances) of the biochemical cascade, scientists risk, at best, getting nothing. In the worst case – to get the "wrong" cells, which will be fatal for the body.

Such different neuronsThe cells of the nervous system are not an exception, but rather a "task with an asterisk".

Growing the right neurons is more difficult than you can imagine. The fact is that populations of nerve cells have several hundred subpopulations, each of which has its own individual "route" of development. Scientists are trying to find these very biochemical "route maps" at the molecular level. Ultimately, this knowledge should help in the treatment of neurodegenerative diseases. After all, many diseases of the nervous system arise due to the dysfunction of only some subpopulations of neurons. Accordingly, it is necessary to restore not all cells, but those specific subpopulations that turned out to be vulnerable to a particular disease.

For example, with amyotrophic lateral sclerosis (ALS), only motor (moto-) neurons die, but even then not all. Those that are responsible for eye movements and bowel movements have a special "immunity". That is, motor neurons are needed for the treatment of ALS, not glia, receptor-specific visual or other nerve cells. Theoretically, the treatment of ALS requires either healthy motor neurons or substances that repair damaged ones.

Previous studies have allowed scientists to describe compounds that help embryonic stem cells to regenerate into differentiated populations. But the purposeful transformation did not work. Instead of the desired type of motor neurons, for some reason, different experimenters always got cells that provide a connection between the central nervous system and the muscles of the cervix (as neuroscientists say, innervate it). So the task, which seemed to be just around the corner, gradually turned into a huge problem.

Neuroscientists led by Mirza Peljto from the Center for the Study of Biology and Pathogenesis of Motor Neurons (Motor Neuron Center for Biology and Disease) also tried to grow motor neurons. This time the ones that innervate the limbs.

Motor Neuron Center for Biology and Disease is a joint brainchild of the University of the District of Columbia Medical Center and the Neurological Institute of New York. It is part of the Neurology Department of the University of the District of Columbia.

It is worth noting that the task is quite multifaceted. After all, the nerve cells of the extremities are located in different parts of the spinal cord (depending on what exactly they control). Moreover, even neurons from the "same team" are very different from each other, since they innervate different muscles of the same organ. That is, scientists had to grow diverse cells that could interact with each other and fully control the work of the innervated part of the body.

Neurons from a test tubeUsing the previously described embryonic compounds, scientists have grown capable motor neurons from embryonic stem cells of a chicken.

However, they did not stimulate the growth of a certain type of neurons by adding certain stimulants (especially those that are not present in the embryo at the early stages of embryo development). Instead, the researchers first recreated the biochemical conditions of embryonic neurogenesis, after which they alternately blocked the work of certain developmental factors. It turned out that for the appearance of full-fledged motor neurons, stem cells need endogenous factors Wnt, FGF and Hh. In the presence of these compounds, the neuronal stem cell becomes exactly the motor neuron that innervates the limbs.

The experimenters tried to find out whether the molecular characteristics of artificially born neurons affect their behavior. That is, whether they will be able to find their own place in the structure of spinal cord neurons or not. To do this, scientists transplanted chicken neurons obtained in vitro into the spinal cord of mouse embryos. It turned out that the cells can independently find the right place. However, the new neurons did not mix with those that appeared during the natural biological process, but kept apart. Scientists believe that this phenomenon can be explained by the fact that the transplanted neurons belong to a chicken, not rodents.

Neuroscientists have not yet been able to find out whether it is possible to influence the number of emerging motor neurons by changing the expression level of Wnt, FGF and Hh. The biochemical background of the point specialization of neurons is also unclear (why each of the cells is responsible for its own muscle and does not climb to others). The researchers note that in the future they intend to answer these questions as well. In the meantime, the main thing is that the resulting neurons were differentiated from the stem cell without the influence of non-embryonic compounds. Moreover, they independently found their destination and turned out to be quite capable. "The results obtained indicate not only that it is possible to obtain differentiated cells naturally (without additional chemical influences), but also open up new opportunities for the study and treatment of diseases such as ALS," the researchers write in the article Functional diversity of ESC–derived motor neuron subtypes revealed through interspinal transplantation, published in the journal Cell Stem Cell.

Portal "Eternal youth" http://vechnayamolodost.ru07.09.2010

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