on (IDD). Objective. To determine the therapeutic potential of MSC-EVs loaded with miRNAs in modulating pathologic changes in IDD. Background. 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. Materials and Methods. Key differentially expressed miRNAs and mRNAs in MSC-EVs were identified using bioinformatics analysis. Three miRNAs (miR-486-5p, miR-3648, and miR-1827) typically downregulated in IDD were selected for further study. The bone marrow-derived MSC-EVs used in this study were cultured in a two-dimensional environment. These MSC-EVs were isolated with the purpose of delivering the selected miRNAs to IDD nucleus pulposus cells in vitro, targeting specifically the upregulated genes (SMAD2, ESR1, MAVS, and MMP14) associated with autophagy and degeneration. Results. MSC-EV treatment led to significant do