Heparan sulfate mimetics accelerate post-injury skeletal muscle regeneration

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Bouvière, Jessica | Trignol, Aurélie | Hoang, Dieu-Huong | del Carmine, Peggy | Goriot, Marie-Emmanuelle | Ben Larbi, Sabrina | Barritault, Denis | Banzet, Sébastien | Chazaud, Bénédicte

Edité par CCSD ; Mary Ann Liebert -

International audience. Although skeletal muscle is capable of complete recovery after an injury, specific situations requires support or acceleration of this process, such as in elderly and athlete, respectively. Skeletal muscle regeneration is due to muscle stem cells that undergo adult myogenesis, a process sustained by muscle stem cell environment. Although recognized as important, extracellular matrix (ECM) has been overlooked in this process. Matrix-based therapy aims at improving ECM remodeling to support tissue repair. In this context, we investigated the properties of a single injection of the clinical grade glycosaminoglycan mimetics RGTA â (ReGeneraTing Agents) on skeletal muscle regeneration in a context compatible with a clinical application, i.e., three days after the injury. Our results show that RGTA â -treated muscles showed an increase of the number of myonuclei in regenerating myofibers and an increase of the capillarization of the new myofibers. In vitro experiments showed that RGTA â directly acts on muscle stem cells by stimulating their fusion into myotubes and on endothelial cells by stimulating the formation and maturation of vessels in a 3D culture set up. These results indicate that a single administration of RGTA â in regenerating muscle stimulated both myogenesis and angiogenesis, thus accelerating skeletal muscle regeneration. Impact statement. Although highly powerful in normal condition, post-injury skeletal muscle regeneration is less efficient in some situations, such as obese, elderly or resting people. In other context, such as high-performance sport, skeletal muscle regeneration must be shortened but in a way ensuring a full functional recovery. In this context, our results show that a single injection of the clinical grade glycosaminoglycan mimetics RGTA â (ReGeneraTing Agents) in a context compatible with a clinical application, i.e. three days after the injury is beneficial for skeletal muscle regeneration, through the stimulation of both myogenesis and angiogenesis.

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