10 March 2009

Satellite cells will repair damaged muscles

Muscles will grow labeled satellites
Pyotr Smirnov, "Newspaper.Ru»Scientists have finally isolated cells capable of regenerating muscle fibers.

In our body, they can become stronger and weaker, but they do not recover when they die. A subpopulation of satellite cells can revive muscles, which is distinguished by three genetic tags and for some reason the immune system does not take it.

Despite the apparent strength and steadfastness of muscle tissue, its restoration remains a serious problem in regenerative medicine. Dosed loads, proper nutrition and regular rest can help in the recovery of damaged muscles. But what to do if there is nothing left to restore or if the muscles are not very prone to regeneration - as, for example, in the case of congenital or acquired dystrophies?

The solution that has become familiar in such cases lately – cell therapy, in which donor cells are "planted" into the damaged organ – is difficult to choose the source of biological material for transplantation.

Bradley Alvin from the University of Colorado and his colleagues were able to find among the numerous cells surrounding the muscle fiber, a population capable of repairing any defect. They turned out to be "satellite side cells" located along each muscle fiber of each of the seven hundred skeletal muscles of our body. The authors of the publication in Stem Cell knew where to look: satellite cells, discovered back in 1961, still haunt scientists to this day.

The fact is that skeletal muscle cells practically do not divide, because each of them is a multi–core spindle, reaching a length of several centimeters, and a diameter of 100 microns or more. Even in embryonic development, progenitor cells merge and form these fiber cells. In the adult state, all the muscle tissue rearrangements are already inside the "spindles" – they simply increase or decrease in size depending on nutrition and training. Satellite cells take part in these rearrangements and changes, merging with the main fiber if necessary.

Due to their large size and multicore nature, the fibers are much more resistant to chemical or physical damage compared to the same nerve cells or independent smooth muscle cells surrounding our vessels.
But if the fiber still dies, then a new one will not appear in its place.

When it comes to the biceps or pectoralis major muscle, the supply of spindles allows you to compensate for the loss, but what to do in the case of the respiratory or fine oculomotor necessary for life? It would seem that it is easier to isolate the mentioned satellites and inject them into the damaged muscle. Unfortunately, such experiments have a reliable, but very weakly expressed and short-lived positive effect.

But there was still an effect, so Alvin and his colleagues decided to catch their bird of happiness in this population. And to no avail: it turned out that the mice "satellites" are not so homogeneous and among them there is also a "side population" of cells, which differs primarily by three genetic markers – ABCG2, Syndecan-4 and Pax7.

In support of their hypothesis about the leading role of these "side satellites" in regeneration, scientists grew new muscle tubes from them in vitro, after which they switched to injections into damaged muscles. mdx mice were "lucky". Like patients with Duchenne myodystrophy, laboratory mice of this line lack the protein dystrophin, which compensates for permanent microtrauma. As a result, their muscles damage themselves with each strong contraction, and when regenerative reserves are exhausted, the process of death can no longer be reversed – after all, we are talking not only about biceps, but also about the same respiratory ones.

After injection of genetically complete labeled "side satellites", 75% of all observed satellite cells in the limb muscles turned out to be "new". Moreover, they regularly updated myofibrils – 30% of the nuclei in these multicore spindles were also updated due to the injected cells. Scientists have demonstrated the same phenomenon for genetically complete rodents whose muscles were poisoned with a solution of barium chloride.

However, despite the extremely positive effects and confirmed working hypotheses, there were no new riddles. When transplanting "satellites" from one mouse line to another, the transplanted cells should have started to disappear after a couple of weeks under the influence of the immune system. Judging by the images of muscle tissue, this did not happen.

In any case, this phenomenon of getting out of control of immunity is in the hands of scientists - after all, it means that the same genetically determined Duchenne dystrophy can be treated without gene therapy.

Portal "Eternal youth" www.vechnayamolodost.ru10.03.2009

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