41.8:
Satellite Stem Cells and Muscular Dystrophy
Satellite or myosatellite cells are multipotent, adult stem cells retained in an inactive state and located near differentiated muscle cells.
These cells are capable of self-renewal, proliferation, and differentiation when muscle regeneration is required. External stimulation or mechanical stress, including physical exercise, activates myosatellite cells.
Some of the same transcription factors used for myoblast activation during normal muscle fiber formation are also used for myosatellite activation during muscle regeneration.
Upon activation, the myosatellite cells first divide, differentiate into myoblasts, and then fuse with damaged myotubes to form mature muscle fibers.
Satellite cells repair damaged muscles in diseases such as Duchenne muscular dystrophy or DMD. DMD is a genetic disorder where a non-functional dystrophin protein leads to a loss of muscle mass.
In DMD, the myosatellite cells fail to adequately regenerate myoblasts for muscle repair. This results in the progressive weakening of the existing muscles, affecting daily life.
41.8:
Satellite Stem Cells and Muscular Dystrophy
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a quiescent state. Thus, myosatellite cells are a source of muscle progenitor cells in postnatal and adult life.
After muscle injury in a normal patient, myosatellite cells can repair damaged muscle cells; however, in patients with muscular dystrophy, the satellite cells fail to repair the damaged muscle. The cell will undergo apoptosis, further causing muscle wastage and eventually death. Muscular dystrophy is a group of diseases, with Duchenne muscular dystrophy (DMD) being the most common. DMD is caused by a mutation in the gene encoding dystrophin. The dystrophin protein connects the cytoskeleton of the muscle cell with the extracellular matrix and stabilizes the plasma membrane. In DMD patients, the dysfunctional dystrophin makes the plasma membrane fragile. Excess calcium ions enter the cell, damaging the muscle fibers. Additionally, white blood cells, such as macrophages, damage the connective tissue surrounding the muscle cell.
Until recently, no treatment was available for muscular dystrophy; however, gene therapy appears to be a promising solution in clinical research trials. The delivered gene encodes for microdystrophin, a shorter version of dystrophin that can function to restore normal muscle activity.
Suggested Reading
- Marieb Elaine N., Katja, Hoehn. Human Anatomy and Physiology. 10th ed. Pearson 2016. p.335
- Mauro A. (1961). Satellite cell of skeletal muscle fibers. The Journal of biophysical and biochemical cytology, 9(2), 493–495.