Therapeutic Potential of MSC-Derived Extracellular Vesicles Carrying miRNAs for Modulating Autophagy and Cellular Degeneration in Intervertebral Disc Degeneration

Study Design. This research utilized bioinformatics and in vitro modeling to assess the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) containing specific microRNAs (miRNAs) on the autophagy and degeneration of nucleus pulposus (NP) cells in intervertebral disc degeneration (IDD). Objective. To determine the therapeutic potential of MSC-EVs loaded with miRNAs in modulating pathological changes in IDD. Summary of Background Data. IDD is characterized by changes in gene expression that contribute to cell degeneration and reduced disc integrity. MSC-EVs are known for their role in cellular communication and potentially reversing these degenerative processes. Methods. Key differentially expressed miRNAs and mRNAs in MSC-EVs were identified using bioinformatics analysis. Three miRNAs (miR-486-5p, miR-3648, miR-1827) typically down-regulated in IDD were selected for further study. The bone marrow-derived MSC-EVs used in this study were cultured in a 2D environment. These MSC-EVs were isolated with the purpose of delivering the selected miRNAs to IDD NP cells in vitro , targeting specifically the upregulated genes (SMAD2, ESR1, MAVS, MMP14) associated with autophagy and degeneration. Results. MSC-EV treatment led to significant downregulation of target genes, enhanced cellular proliferation, and decreased apoptosis and autophagy. Overexpression of these target genes produced the opposite effects, confirming the miRNAs’ regulatory roles. Conclusions. MSC-EVs carrying specific miRNAs can effectively modulate gene expression, reduce degenerative processes, and promote cellular proliferation in IDD, indicating a promising therapeutic strategy for treating IDD and potentially other degenerative diseases. Further investigations are warranted to explore MSC-EV applications in regenerative medicine.