{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:02:21Z","timestamp":1789441341013,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","award":["NRRP PNC\u2010E3\u20102022\u201023683269 PNC\u2010HLS\u2010TA"],"award-info":[{"award-number":["NRRP PNC\u2010E3\u20102022\u201023683269 PNC\u2010HLS\u2010TA"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) are emerging as a promising cell\u2010free strategy for intervertebral disc degeneration (IDD) treatment. This study aimed to evaluate the anabolic effect of Wharton's Jelly MSC (WJ\u2010MSC)\u2010derived EVs on degenerative human nucleus pulposus cells (hNPCs) under in\u00a0vitro inflammation using a 3D culture model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Following isolation, hNPCs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) were encapsulated in alginate beads and treated with 10, 50, and 100\u2009\u03bcg\/mL of WJ\u2010MSC\u2010EVs after preincubation with 10\u2009ng\/mL interleukin (IL)\u20101\u03b2. Cell proliferation, viability, nitrite production, and glycosaminoglycan (GAG) content were assessed. Histological analyses evaluated extracellular matrix (ECM) production. Phenotypic (SOX9, KRT19), catabolic (MMP1, MMP13, ADAMTS5, IL6, NOS2), and anabolic (ACAN) ECM markers were analyzed by RT\u2010qPCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WJ\u2010MSC\u2010EVs significantly promoted hNPC proliferation at all concentrations, with 10\u2009\u03bcg\/mL effectively counteracting IL\u20101\u03b2 catabolic effects. Live\/dead staining showed reduced cell death in EV\u2010treated hNPCs compared to the IL\u20101\u03b2\u2010only group. Nitrite production decreased after 7\u2009days with 10\u2009\u03bcg\/mL WJ\u2010EVs, supported by reduced NOS2 expression. GAG content increased dose\u2010dependently, as confirmed by Alcian blue staining. WJ\u2010EVs positively modulated anabolic (ACAN, KRT19, SOX9), catabolic (ADAMTS5, MMP1, MMP13), and inflammatory (IL6) gene expression levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>WJ\u2010MSC\u2010derived EVs demonstrate potential as a cell\u2010free therapeutic approach for IDD by enhancing hNPC growth, mitigating ECM degradation, and reducing oxidative stress\u2010related IDD progression. These findings warrant further investigation into the use of WJ\u2010EVs for IDD treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70106","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T14:08:58Z","timestamp":1755698938000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Wharton's Jelly Mesenchymal Stromal\u00a0Cell\u2010Derived Extracellular Vesicles Attenuate Intervertebral Disc Degeneration Under Inflammatory Stress in an In\u00a0Vitro\n                    <scp>3D<\/scp>\n                    Culture System"],"prefix":"10.1002","volume":"8","author":[{"given":"Veronica","family":"Tilotta","sequence":"first","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome 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