Local injection of human umbilical cord mesenchymal stem cells () and their derived exosomes significantly mitigated muscle atrophy in rat gastrocnemius muscle following nerve injury.
Human umbilical cord MSCs (hucMSCs) and hucMSC-derived exosomes () were evaluated for their effects on muscle atrophy after sciatic nerve crush injury.
In vitro studies showed that hucMSC-EXOs alleviated atrophy in L6 myotubes.
Mechanistic analysis revealed that hucMSC-EXOs treatment increased levels in L6 myotubes.
MiR-23b-3p was found to inhibit the expression of muscle-specific ubiquitin ligases Fbxo32 and Trim63, which are associated with muscle atrophy.
An inhibitor of miR-23b-3p reversed its protective effects on myotube atrophy in vitro.
Simplified
Cell therapy based on mesenchymal stem cells (MSCs) alleviate muscle atrophy caused by diabetes and aging; however, the impact of human umbilical cord mesenchymal stem cells on muscle atrophy following nerve injury and the underlying mechanisms remain unclear. In this study, we evaluated the therapeutic efficacy of human umbilical cord MSCs () and hucMSC-derived exosomes () for muscle atrophy following nerve injury and identified the underlying molecular mechanisms. Sciatic nerve crush injury in rats and the induction of myotubes in L6 cells were used to determine the ameliorating effect of hucMSCs and hucMSC-EXOs on muscle atrophy. Q-PCR and Western blot analyses were used to measure the expression of muscle-specific ubiquitin ligases Fbxo32 (Atrogin1, MAFbx) and Trim63 (MuRF-1). Dual-luciferase reporter gene experiments were conducted to validate the direct binding of miRNAs to their target genes. Local injection of hucMSCs and hucMSC-EXOs mitigated atrophy in the rat gastrocnemius muscle following sciatic nerve crush injury. In vitro, hucMSC-EXOs alleviated atrophy in L6 myotubes. Mechanistic analysis indicated the upregulation of levels in L6 myotubes following hucMSC-EXOs treatment. MiR-23b-3p significantly inhibited the expression of its target genes, Fbxo32 and Trim63, and suppressed myotube atrophy. Notably, an miR-23b-3p inhibitor reversed the inhibitory effect of miR-23b-3p on myotube atrophy in vitro. These results suggest that hucMSCs and their exosomes alleviate muscle atrophy following nerve injury. MiR-23b-3p in exosomes secreted by hucMSCs contributes to this mechanism by inhibiting the muscle-specific ubiquitination ligases Fbxo32 and Trim63.
Key numbers
1×
Decrease in Muscle Atrophy
Comparison of muscle atrophy between treatment and control groups.
100 μm
Increase in Myotube Diameter
Average diameter of myotubes treated with .
50%
Reduction in Ubiquitin Ligases
Percentage decrease in mRNA expression of ubiquitin ligases in treated muscles.
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