September 2021

Chemical Cocktail Promotes Muscle Damage Repair

Schematic illustrating small molecules interacting with muscle stem cells. Image courtesy of Li Laboratory at UCLA.

University of California, Los Angeles (UCLA) researchers have identified a drug cocktail that can activate and expand a population of muscle stem cells, which are either resident in the muscle, or are isolated from other tissues, such as the skin. The researchers found that the muscle stem cells could heal damaged tissue in adult mice, aged mice (which have a reduced ability to heal), and a mouse model of muscular dystrophy (which displays severe muscle wasting). This work has implications for patients with muscle injury or chronic muscle wasting.

The drug cocktail includes forskolin, a chemical found in plants that increases the production of an important signaling molecule in cells. Also in the cocktail is a small molecule called RepSox, which mediates stem cell differentiation. While both of these compounds have been used in stem cell research, their combined effect on muscle stem cell proliferation and differentiation was a novel finding in this study, said Song Li, PhD, a professor in the departments of bioengineering and medicine at UCLA.

The researchers used their cocktail to selectively expand a population of chemically induced muscle stem cells, which were then implanted into the muscles of pre-injured mice. After 4 weeks, the implanted stem cells facilitated muscle repair and tissue regeneration in all of their models. Li and colleagues then wanted to see if they could activate and expand the mice’s resident muscle stem cell population by delivering the cocktail directly into the muscles. The drug cocktail was loaded into nanoparticles, allowing for the controlled release of the cocktail over 2 weeks, and injected it into the muscles of pre-injured adult or aged animals. Compared with mice injected with empty nanoparticles, mice injected with the drug-loaded nanoparticles had markedly improved muscle regeneration and function.

“This work represents a promising step forward in the field of tissue regeneration and could potentially lead to a more efficient method of repairing damaged muscle,” said David Rampulla, PhD, director of the division of Discovery Science & Technology at the National Institute of Biomedical Imaging and Bioengineering, which provided funding for the work.

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