Until now, no cure was available for muscular dystrophy. However, recent research findings are about to change that. Se-Jin Lee, from the Hopkins School of Medicine, published an article in Proceedings of the National Academy of Sciences about a promising solution for muscle hypertrophy that does not involve stem cells.
Satellite cells are the rare stem cells of muscles. They work by differentiating and fusing either to augment muscle fibers or to form new fibers. This process is indispensable in the maintenance of muscle cells. Specifically, these cells serve to increase and replace muscle mass after exercise or injury.
Satellite cells are mostly dormant in mammals (including humans), which means that they neither differentiate nor undergo cell division. Their activation occurs in response to a strain stimulus, which subsequently causes the satellite cells to enter the cell cycle.
However, certain diseases and aging can cause satellite cells to lose their ability to stay dormant. They are thus unable to function when needed. For instance, in the case of muscle dystrophy, it was found that the satellite cells are exhausted.
While satellite cells take care of the primary regulations in normal muscle cells, other proteins, such as myostatin and activin, also assist in maintenance functions. Specifically, it is known that myostatin work with activin to limit muscle growth. However, their role in relation to these satellite cells is still unclear.
Lee wanted to determine how to generate muscle mass when satellite cells are exhausted.
He observed an increase in muscle mass in myostatin knockouts. Myostatin knockouts result in the inhibition of the myostatin/activin pathway. Naturally, this led researchers to ask: What are the targets of this pathway? What role do satellite cells, the stem cells of muscles, and myofibers play in this signaling pathway?
The researchers reasoned that if the inhibition of myostatin/activin induces hypertrophy by activating the satellite cells and causing them to fuse with the myofibers, then muscle hypertrophy should not be observed if the satellite cells are damaged or absent.
To verify this hypothesis, researchers started by looking at the effect of myostatin/activin in mice that either lacked satellite cells or did not have functioning ones. Results showed an increase in muscle mass. The increase in muscle cells was solely due to hypertrophy of the muscle fibers, suggesting that proper function of the pathway does not require satellite cells.
In a second experiment, myostatin was inhibited pharmacologically. Subsequent results showed that muscle growth occurred even though the satellite cells did not fuse. This means that myostatin inhibition does not target satellite cells.
Finally, researchers looked at the effect of modifying the myofibers by turning off the gene for myostatin/activin receptors. Without these receptors, hypertrophy of muscles cells was still present in the mutant mice.
Together, the results suggest that satellite cells play virtually no role in the inhibitory pathway. Instead, myofibers are the principal target for the myostatin/activin pathway. These findings imply that regeneration of muscle cells is possible even without satellite cells.
This research leads to exciting new possibilities because it opens the door to a new way of curing diseases characterized by muscle loss. It has been estimated that around 50,000 Americans suffer from disabilities caused by muscular dystrophy.
Implementing this research would offer an alternative option to surgeries and stem cells, and could offer radical results with a low-maintenance treatment plan.
The treatment is currently being made available in clinical trials for people who are suffering from muscular dystrophy. This treatment could also be applied to the older population, since we experience a loss of muscle mass from exhaustion of satellite cells as we age.