Skeletal-muscle regeneration via the chemical induction and expansion of myogenic stem cells in situ or in vitro

Muscle loss and impairment resulting from traumatic injury can be alleviated by therapies using muscle stem cells. However, harvesting sufficient numbers of autologous myogenic stem cells and expanding them efficiently has been challenging. Here, we show that myogenic stem cells (predominantly Pax7(+) cells) selectively expanded from readily obtainable dermal fibroblasts or skeletal muscle stem cells via a specific cocktail of small molecules and transplanted into muscle injuries in adult, aged or dystrophic mice led to functional muscle regeneration in the three animal models, and that sustained release of the small-molecule cocktail in situ via polymer nanoparticles also led to muscle repair by inducing the robust activation and expansion of resident satellite cells. Chemically induced stem cell expansion in vitro and in situ may prove advantageous for stem cell therapies aiming to regenerate skeletal muscle and other tissues.