Fetal muscle stem cell-derived exosomes improve dexamethasone-induced muscle atrophy at the single muscle fiber level.

This study investigated the therapeutic potential of exosomes derived from fetal muscle stem cells (FMSC-Exos) in mitigating dexamethasone (DEX)-induced muscle atrophy in a mouse model. Kunming (KM) mice were utilized to visualize muscle atrophy at the single muscle fiber level through an optimized isolation technique. Following the induction of muscle atrophy by dexamethasone, mice were treated with FMSC-Exos via local intramuscular injection into the gastrocnemius muscle. Results demonstrated that exosome administration showed a trend towards improved body weight and significantly increased muscle mass and individual muscle fiber diameter compared to the dexamethasone-only group. Histological analysis confirmed that FMSC-Exos effectively alleviated muscle fiber atrophy and promoted regeneration. RT-PCR and Western blot analyses revealed differential expression of the muscle atrophy markers MuRF1 and MAFbx/Atrogin-1. The mRNA expression levels of these atrophy-related factors were significantly elevated in the DEX-treated group compared to the control. Although expression levels in the exosome treatment group remained higher than control, they were significantly lower than in the DEX group. Protein expression followed a similar trend, indicating that dexamethasone modulates MuRF1 and MAFbx at both transcriptional and translational levels, and that exosome treatment counteracts this effect, promoting a restoration towards normal muscle protein expression homeostasis.