Rejuvinating stem cells could repair muscle in diseases like muscular dystrophy

Giving repair cells a helping hand. Double-M, CC BY

Skeletal muscle is the tissue that makes our bodies move in a voluntary way, so we can walk, run, and breath. This tissue is generated and maintained by a population of specialised stem-like cells called satellite cells. These cells repair damage from wear and tear such as that caused by jogging or trauma. As we get older, these cells gradually lose their capacity to carry out repairs, but we didn’t really know why.

But it turns out that as we age, the cells responsible for helping to maintain, repair and build our muscle tissue are not exhausted. They are simply not being given the right instructions to carry out the work. Changing this communication problem could provide a way to treat muscular dystrophy.

In new research into these satellite cells, published in Nature Medicine, we discovered why these calls are progressively less able to repair skeletal muscle in our golden years. Our discovery also opens the way for drugs to be found that could help people with muscle-wasting diseases like muscular dystrophy.

Role of stem cells in repair

Stem cells that are specialised for different tissue types exist throughout our adult bodies and are responsible for the maintenance and repair of those tissues. Satellite cells in skeletal muscle are normally dormant, but when our muscles experience stress, from taking too much weight or because of injury, these cells begin to respond. First they divide symmetrically, giving rise to two “daughter” satellite cells. This division continues until there is a good pool of muscle-making daughter cells. Then they divide asymmetrically, producing one stem cell (satellite stem cell) and another cell committed to becoming muscle tissue (satellite myogenic cells).

Controlling the choice between symmetric and asymmetric stem cell divisions is a key step that affects the efficiency of tissue generation. In previous studies we found that a protein called Wnt7a stimulates symmetric cell divisions, which creates more stem cells. This increases the population of the muscle-making satellite cells overall, and this dramatically accelerates muscle repair.

Dampening the signal

Cells in our bodies use chemical signals like Wnt7a to send instructions from outside the cell to inside the cell, turning specific genes on or off. This is called a signalling pathway. By analysing which genes are turned on or off in old versus young satellite cells, we made the surprising discovery that as muscle stem cells age, a specific signalling pathway, called Jak/Stat, dramatically increased.

By blocking this pathway, we increased the symmetric cell division, which restored the function of aged satellite cells to youthful levels. Our results suggest that as we get older our body simply doesn’t send the right signals to maintain the numbers of functional satellite stem cells.

When we used drugs to dampen the Jak/Stat signal, we dramatically enhanced muscle repair and growth. Using this technique, we might be able to help the body repair itself through cell or gene-therapy. This would be especially beneficial for muscle-wasting diseases such as muscular dystrophy.

Drugs that stimulate stem cells to repair damage are now emerging for the treatment of a variety of diseases, from brain damage and heart attack to muscular dystrophy. And our research shows how therapeutics that target satellite cells to treat these kinds of muscle diseases is achievable. Finding and developing them must now be a priority.