12 November 2010

Stem cell transplantation against senile muscle atrophy

Young muscles willingly increase in volume in response to regular loads and are capable of almost complete recovery even with fairly extensive injuries. The myofibrils themselves are not capable of dividing, and satellite stem cells provide replacement of worn–out muscle fibers, working muscle hypertrophy and their regeneration (they are called satellite "satellites" because they are located around myofibrils).

With age, a complex of changes develops in muscle cells and muscles in general, leading to sarcopenia – age-related atrophy of the musculature, resulting in loss of muscle mass, slowing down the process of regeneration and contractility of muscles.

Although the mechanisms responsible for this are not completely clear, it is known that a decrease in the activity of satellite cells plays an important role in the development of sarcopenia. Violation of their function also occurs in some hereditary forms of myodystrophy, manifested already at a young age.

In experiments on the regeneration of muscle tissue, scientists from two American universities – Washington and Colorado (in Boulder) received interesting and possibly promising results for medicine.

The researchers did not think about senile muscle atrophy: the purpose of their work was to study the regeneration of muscle tissue after injury. In artificially damaged (by injections of barium chloride) limb muscles of three-month-old mice, scientists injected myofibrils of young donor mice together with 10-50 stem cells surrounding them.

The fact that the wounds healed much faster at the same time was quite a predictable result. And even the fact that the muscles treated with stem cells began to increase in size (their mass became twice as large as usual) is also an understandable result. However, the researchers assumed that this is a temporary phenomenon and in a few months the volume of the limbs will return to normal. But muscle hypertrophy in experimental mice, although slightly decreased, but persisted until the end of life: the transplanted stem cells retained the ability to divide and prevented senile muscle atrophy.

By the age of two (deep mouse old age), the "pumped up" muscles were one and a half times more in weight and by 170% (2.5-3 times!) – in a circle. This turned out to be a complete surprise for the experimenters. By the way, despite the active division of satellite cells, no signs of tumor development were observed after their introduction.

Unfortunately, muscle hypertrophy, and even for the rest of his life, was observed only when the injection of donor stem cells was combined with trauma. In intact muscles, after the introduction of stem cells, neither the volume nor the mass increased – perhaps due to the absence of some signaling substances released by dying muscle fibers.

Nevertheless, the results obtained may well someday help not only in the treatment of congenital muscular dystrophy (for example, donor cells could replace their own, dying with Duchenne myodystrophy), but also in countering senile muscle degradation.

However, it remains to be checked whether the same effect will be observed when introducing young stem cells into aging muscles, whether this technique will work not only on skeletal muscles, but also in oculomotor, heart, diaphragm… And a lot more will have to be studied and rechecked.

The researchers hope that in the course of further experiments they will be able to find low-molecular compounds or combinations of them that will stimulate the activity of patients' own satellite cells.

Scientists have already started experiments in which they intend to first check whether it is possible to get the same effect when introducing human or large animal satellite cells to mice. After that, it will be possible to think about the possibility of research on volunteers with chronic myodystrophy.

Article by John K. Hall et al. Prevention of Muscle Aging by Myofiber-Associated Satellite Cell Transplantation is published in the latest issue of the journal Science Translational Medicine (unfortunately, not in the public domain).

Alexander Chubenko
Portal "Eternal youth" http://vechnayamolodost.ru 
based on the materials of the press release of the University of Colorado at Boulder:
Stem cell transplants in mice produce lifelong enhancement of muscle mass12.11.2010

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