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Understanding the molecular mechanisms underlying this condition is essential for developing targeted therapies. Among these mechanisms, microRNAs (miRNAs) have emerged as critical post\u2010transcriptional regulators of gene expression in IVD cells, influencing key processes such as extracellular matrix (ECM) homeostasis, inflammatory signalling and cellular senescence. Extracellular vesicles (EVs), which transport miRNAs between cells, represent a promising avenue for therapeutic intervention. However, the composition of their miRNA cargo across different stages of disc degeneration remains inadequately characterised. We isolated EVs from primary human IVD cells derived from non\u2010degenerate, mildly degenerate, and severely degenerate tissues, and performed small RNA sequencing to profile their miRNA content. Bioinformatic analyses revealed enrichment in pathways related to ECM\u2010receptor interaction, focal adhesion, inflammation and cell cycle regulation. Notably, let\u20107b\u20105p and miR\u2010100\u20105p were among the most abundant miRNAs and were significantly lower in EVs from degenerate discs. Functional assays demonstrated that transfection of IVD cells with let\u20107b\u20105p or miR\u2010100\u20105p mimics individually suppressed IL\u20101\u00df expression at both mRNA and protein levels, confirming their anti\u2010inflammatory roles. Strikingly, co\u2010delivery of both miRNAs enhanced suppression of pro\u2010inflammatory mediators, reduced senescence\u2010associated\n                    <jats:italic>p16<\/jats:italic>\n                    expression and upregulated\n                    <jats:italic>TIE2<\/jats:italic>\n                    mRNA, indicating synergistic effects in promoting a regenerative cell phenotype. These findings highlight the regulatory roles of EV\u2010enriched let\u20107b\u20105p and miR\u2010100\u20105p in modulating inflammation and senescence in IVD cells, and underscore the potential of miRNA\u2010loaded EVs as cell\u2010free regenerative therapies for disc degeneration.\n                  <\/jats:p>","DOI":"10.1002\/jex2.70127","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T11:11:55Z","timestamp":1775560315000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Beyond miRNA Cargo Profiles: Anti\u2010Inflammatory Roles of Extracellular Vesicle\u2010Enriched miRNAs Derived From Human Intervertebral Disc Cells Unveiled by Functional Testing"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6342-0633","authenticated-orcid":false,"given":"Li","family":"Li","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of 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