High-intensity ultrasound irradiation promotes the release of extracellular vesicles from C2C12 myotubes.

Skeletal muscle is an important secretory organ in mammals, producing myriad chemical mediators ("myokines") with distinct biological action in different tissues, including anti-inflammatory activity. Extracellular vesicles (EVs) have recently been identified as a mode of myokine transport from muscle, facilitating such anti-inflammatory activity. In this report, we have demonstrated that high-intensity ultrasound (US) strongly induces EV secretion from cultured myotubes without a reduction in cell viability. High-intensity US of 3.0 W/cm2 with 20% duty cycle increased the number of EVs by 2-fold compared to control at 6 h. This effect was specific to EVs in the 100-150 nm size range. Thus, high-intensity US is a novel modality for inducing myocellular EV release and may hold therapeutic value.