• LinFeng Wang, Yang Wang, Jianhang Jiao, Weibo Jiang, Tong Yu, Zhonghan Wang, Mufeng Li, Minfei Wu, and Pan Su.
• Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, China.
• Spine. 2025 Jan 1; 50 (1): E7E19E7-E19.

Study DesignThis 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 cells in intervertebral disc degeneration (IDD).ObjectiveTo determine the therapeutic potential of MSC-EVs loaded with miRNAs in modulating pathologic changes in IDD.BackgroundIDD 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 MethodsKey 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.ResultsMSC-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.ConclusionsMSC-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.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

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