Mechanical strain drives exosome production, function, and miRNA cargo in muscle progenitor cells

Mesenchymal stem cells (MSCs) have been proven to promote tissue repair. However, concerns related to their clinical application and regulatory hurdles remain. Recent data has demonstrated the pro-regenerative secretome of MSCs can result in similar effects in the absence of the cells themselves. Within the secretome, exosomes have emerged as a promising regenerative component. Exosomes, which are nanosized lipid vesicles secreted by cells, encapsulate miRNA, RNA, and proteins that drive MSCs regenerative potential with cell specific content. As such, there is an opportunity to optimize the regenerative potential of MSCs, and thus their secreted exosome fraction, to improve clinical efficacy. Exercise is one factor that has been shown to improve muscle progenitor cell function and regenerative potential. However, the effect of exercise on MSC exosome content and function is still unclear.

Researchers at the Steadman Philippon Research Institute used an in vitro culture system to evaluate the effects of mechanical strain, an exercise mimetic, on C2C12 (muscle progenitor cell) exosome production and pro-regenerative function. Their results indicate that the total exosome production is increased by mechanical strain and can be regulated with different tensile loading regimens. Furthermore, they found that exosomes from mechanically stimulated cells increase proliferation and myogenic differentiation of naïve C2C12 cells. Lastly, the researchers show that exosomal miRNA cargo is differentially expressed following strain. Gene ontology mapping suggests positive regulation of BMP signaling, regulation of actin-filament based processes, and muscle cell apoptosis may be at least partially responsible for the pro-regenerative effects of exosomes from mechanically stimulated C2C12 muscle progenitor cells.


A) Cells treated with exosomes from mechanically strained cell proliferate faster B) P-value comparisons for all values. C) 2-way ANOVA with Turkey’s HSD results

Mullen M, Williams K, LaRocca T, Duke V, Hambright WS, Ravuri S, Bahney C, Ehrhart N, Huard J. (2022) Mechanical Strain Drives Exosome Production, Function, and miRNA Cargo in C2C12 Muscle Progenitor Cells. J Orthop Res [Epub ahead of print]. [abstract]

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