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Physical exercise is shown to effectively delay the progression of IVDD by enhancing ECM synthesis and reducing inflammation. However, many individuals are unable to maintain regular exercise habits due to physical limitations and insufficient self\u2010discipline. In response to this challenge, the concept of exercise mimetic exosomes (EMEs) is proposed as a therapeutic strategy for IVDD. In this approach, human induced pluripotent stem cell\u2010derived myotubes are subjected to mechanical strain to simulate exercise conditions. The exosomes generated under these conditions, termed EMEs, are enriched with exercise\u2010inducible components, notably irisin. These EMEs are capable of being internalized by both NPCs and macrophages. In NPCs, EMEs restored ECM metabolic balance and inhibited NF\u03baB activation. In macrophages, EMEs modulated the M1 polarization induced by degenerated NPCs. Collectively, EMEs restored the metabolic equilibrium of the extracellular matrix and mitigated inflammatory macrophage infiltration within the microenvironment, thereby demonstrating significant therapeutic effects on IVDD. More importantly, EMEs may serve as a model for the treatment of other musculoskeletal disorders and the development of exercise mimetic therapies.<\/jats:p>","DOI":"10.1002\/adhm.202500219","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T03:35:07Z","timestamp":1747625707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exercise Mimetic Exosomes Re\u2010establish the Extracellular Matrix Metabolic Balance and Alleviate the Inflammatory Macrophage Infiltration in Intervertebral Disc Degeneration"],"prefix":"10.1002","volume":"14","author":[{"given":"Ke","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Wangjing Hospital China Academy of Chinese Medical Sciences Beijing 100102 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhi","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of 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