Athletes, the elderly, and those with degenerative muscle disease would all benefit from accelerated muscle repair. Normally, when skeletal muscles, those connected to the bone, are injured, muscle stem cells wake up from a dormant state and repair the damage.

When muscles age, however, stem cell number and function declines, as do both tissue function and regenerative ability. A Carnegie Institute of Science team, including researchers from the University of Missouri, investigated muscle stem cell pool size and asked if stem cell number could be increased, and if there would be any associated functional benefits.

Muscle stem cells, called satellite cells, are cells that promote growth, repair and regeneration. As team leader Christoph Lepper explained: "These satellite cells make up some 5-7% of all muscle cells and are essential to muscle regeneration. When a mouse is born, the satellite cells divide and differentiate for about 3 to 4 weeks driving tissue growth. They then go quiet until an injury is detected. The number of satellite cells set aside at this time appears to be relatively constant with regard to the host muscle tissue size. We wanted to see whether this ratio could be manipulated and, if so, whether there would be any physiological consequences."

This study facilitated the surprising discovery that the muscle fiber can "communicate" to its stem cells to influence the stem cell pool size. This molecular communication to the satellite cells was the origin of a six-fold stem cell increase.

"We were very surprised to find that it was possible to uncouple the number of stem cells from the host tissue size without seeing negative consequences to muscle physiology," remarked Sheryl Southard, co-lead author on the paper with Ju-Ryoung Kim. Remarkably, the increased number allowed muscles to regenerate much faster after injury.

Importantly, the scientists found that in a mouse model for Duchenne muscular dystrophy, the effect stunted the wasting disease.

After noting the increase in the number of satellite cells, without any changes to overall muscle size, the researchers hope to discover the molecular cascade that regulates muscle stem cell number and the "stop" and "go" signals that cause the cells to differentiate and go quiet.

The study is published in the October 11, 2016, issue of eLife. Learn more from: Carnegie Institute of Science