Hyaluronic acid, a naturally occurring compound, awakens stem cells to repair damaged muscles

A new study published in the journal Science reveals a unique form of cellular communication that drives muscle repair. In damaged muscle, stem cells must work with immune cells to complete the repair process, but how these cells coordinate to ensure dead tissue is efficiently removed before new muscle fibers are formed is still unknown. Scientists have now shown that a natural compound called hyaluronic acid, used in cosmetics and in injections for osteoarthritis, is the key molecule that controls this fundamental interaction.

“When muscles become damaged, it’s important that immune cells quickly invade the tissue and repair the damage before the stem cells start repairing,” said Dr. Jeffrey Dilworth, principal investigator at Ottawa Hospital and professor at the University of Ottawa and senior author on the study. “Our study shows that muscle stem cells are primed to start repairing immediately, but the immune cells keep the stem cells in a dormant state while they finish the cleaning job. After about 40 hours, when the cleaning job is done, an internal alarm goes off in the muscle stem cells, allowing them to wake up and start repairing.”

dr Dilworth and his team identified hyaluronic acid as a key component of this internal alarm clock that tells muscle stem cells when to wake up. When muscle damage occurs, the stem cells start producing and coating with hyaluronic acid. If the coating is thick enough, it blocks the immune cells’ sleep signal and allows the muscle stem cells to wake up.

Using mouse and human tissue, Dr. Dilworth and his team also study how muscle stem cells control the production of hyaluronic acid using epigenetic marks on the Has2 gene.

“Interestingly, aging is associated with chronic inflammation, muscle weakness, and a decreased ability of muscle stem cells to wake up and repair damage,” said lead author Dr. Kiran Nakka, a research associate of Dr. Dilworth, who conducted this research as part of his postdoctoral studies. “If we could find a way to increase hyaluronic acid production in the muscle stem cells of older people, it could help with muscle repair.”

The authors note that the regenerative effects of hyaluronic acid appear to depend on its being produced by muscle stem cells. The team is currently investigating whether drugs that alter the epigenetics of muscle stem cells could be used to increase their production of hyaluronic acid.