A Caution on Muscle Stem Cells

A lot of the present work on stem cell biology in aging focuses on the muscle stem cells known as satellite cells. This includes some of the interesting lines of research aimed at restoring the activity of old stem cell populations via the use of signal molecules such as GDF-11 identified in parabiosis studies. This open access paper is a caution for those following the field, noting that outside of limb muscles comparatively little is known of the biochemistry of muscle stem cells, and they are perhaps better thought of as scores of different populations with different characteristics, one per muscle group. In other words there is probably a lot more work ahead here than you might have thought was the case:

The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies (MDs), such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some MDs. The biology of muscle stem cells varies depending on the muscles with which they are associated, and such diversity likely contributes to the pathologic sensitivities of different skeletal muscles to aging and disease.

Skeletal muscles are composed of myofibers, large syncytial cells containing hundreds of post-mitotic myonuclei. Juxtaposed between the basal lamina and the myofiber cell membrane, satellite cells reside at the periphery of skeletal myofibers. Recent studies have demonstrated that satellite cells expressing paired box protein 7 (Pax7) are the primary myogenic cell required for muscle regeneration. The majority of knowledge concerning satellite cell biology arises from studies examining larger muscles of the limbs, which collectively represent less than 2% of all skeletal muscles. Intriguingly, satellite cells present in other muscle groups, including trunk, diaphragm, larynx, tongue, extraocular, masseter, and pharynx, deviate from the canonical biology of their limb counterparts.

Unfortunately, little is known about the effects of age or disease on non-limb muscles as a whole or what factors predispose them to the effects of pathologic conditions. Additionally, satellite cells could serve as pathologic determinants in some dystrophies; however, our knowledge of non-limb satellite cells and their role in muscle biology is severely lacking. Recognizing and elucidating the distinct differences in satellite cell biology between different skeletal muscles could be the key to unraveling the conundrum of muscle specificity between the various MDs.

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595652/

Comments

"In other words there is probably a lot more work ahead here than you might have thought was the case"

or probably not:

"Generation of an expandable intermediate mesoderm restricted progenitor cell line from human pluripotent stem cells"

http://elifesciences.org/content/4/e08413

Posted by: alc at November 10th, 2015 11:36 AM
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