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Recent studies show that extracellular vesicles (EVs) from bone marrow\u2010derived mesenchymal stem cells (BMSCs) contribute to joint homeostasis and OA management. However, the impact of donor age on BMSC\u2010derived EV efficacy remains underexplored. In this study, we investigated EV efficacy from young BMSCs (2\u2010month\u2010old) in mitigating OA, contrasting them with EVs from aged BMSCs (27\u2010month\u2010old). The study used destabilisation of the medial meniscus (DMM) surgery on mouse knee joints to induce accelerated OA. Cartilage degeneration markers and senescence markers' expression levels were investigated in response to EV treatment. The therapeutic impact of EVs on chondrocytes under inflammatory responses was also evaluated. Despite having similar morphologies, EVs from young BMSCs markedly decreased senescence and improved chondroprotection by activating the PTEN pathway while simultaneously suppressing the upregulation of the PI3K\/AKT pathways, proving to be more effective than those from older BMSCs in\u00a0vitro. Furthermore, intraperitoneal injections of EVs from young donors significantly mitigated OA progression by preserving cartilage and reducing synovitis in a surgical OA model using DMM in mice. These findings highlight that donor age as a critical determinant in the therapeutic potential of BMSC\u2010derived EVs for clinical use in OA treatment.<\/jats:p>","DOI":"10.1111\/cpr.13776","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T08:21:09Z","timestamp":1734682869000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Comparative Analysis of the Therapeutic Potential of Extracellular Vesicles Secreted by Aged and Young Bone Marrow\u2010Derived Mesenchymal Stem Cells in Osteoarthritis Pathogenesis"],"prefix":"10.1111","volume":"58","author":[{"given":"Shital","family":"Wakale","sequence":"first","affiliation":[{"name":"Centre for Biomedical Technologies Queensland University of Technology  Brisbane Australia"},{"name":"School of Mechanical, Medical &amp; Process Engineering Queensland University of Technology  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shenzhen Hospital of Southern Medical University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia Rujia","family":"Sun","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Technologies Queensland University of Technology  Brisbane Australia"},{"name":"School of Mechanical, Medical &amp; Process Engineering Queensland University of Technology  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chamikara","family":"Liyanage","sequence":"additional","affiliation":[{"name":"Cancer Single Cell Genomics Laboratory Translational Breast Cancer Program, Olivia Newton\u2010John Cancer Research Institute  Heidelberg Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Gunter","sequence":"additional","affiliation":[{"name":"Australian Prostate Cancer Research Centre\u2010Queensland, Centre for Genomics and Personalised Health, School of Biomedical Science Queensland University of Technology, Translational Research Institute  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyotsna","family":"Batra","sequence":"additional","affiliation":[{"name":"Australian Prostate Cancer Research Centre\u2010Queensland, Centre for Genomics and Personalised Health, School of Biomedical Science Queensland University of Technology, Translational Research Institute  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Crawford","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Technologies Queensland University of Technology  Brisbane Australia"},{"name":"Orthopaedic Department The Prince Charles Hospital  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxun","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shenzhen Hospital of Southern Medical University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5057-2427","authenticated-orcid":false,"given":"Indira","family":"Prasadam","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Technologies Queensland University of Technology  Brisbane Australia"},{"name":"School of Mechanical, Medical &amp; Process Engineering Queensland University of Technology  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2010.03.001"},{"key":"e_1_2_10_3_1","first-page":"646","article-title":"Burden of Major Musculoskeletal Conditions","volume":"81","author":"Woolf A. 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