{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:57:43Z","timestamp":1792789063299,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["Ricerca Corrente"],"award-info":[{"award-number":["Ricerca Corrente"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The study of the miRNA cargo embedded in extracellular vesicles (EVs) released from adipose-derived mesenchymal stromal cells (ASC) preconditioned with IL-1\u03b2, an inflammatory stimulus driving osteoarthritis (OA), along with EVs-cartilage dynamic interaction represent poorly explored fields and are the purpose of the present research. ASCs were isolated from subcutaneous adipose tissue and EVs collected by ultracentrifugation. Shuttled miRNAs were scored by high-throughput screening and analyzed through bioinformatics approach that predicted the potentially modulated OA-related pathways. Fluorescently labeled EVs incorporation into OA cartilage explants was followed in vitro by time-lapse coherent anti-Stokes Raman scattering; second harmonic generation and two-photon excited fluorescence. After IL-1\u03b2 preconditioning, 7 miRNA were up-regulated, 4 down-regulated, 37 activated and 17 silenced. Bioinformatics allowed to identify miRNAs and target genes mainly involved in Wnt, Notch, TGF\u03b2 and Indian hedgehog (IHH) pathways, cartilage homeostasis, immune\/inflammatory responses, cell senescence and autophagy. As well, ASC-EVs steadily diffuse in cartilage cells and matrix, reaching a plateau 16 h after administration. Overall, ASCs preconditioned with IL-1\u03b2 allows secretion of EVs embedded with a chondro-protective miRNA cargo, able to fast penetrate in collagen-rich areas of cartilage with tissue saturation in a day. Further functional studies exploring the EVs dose-effects are needed to achieve clinical relevance.<\/jats:p>","DOI":"10.3390\/cells10051180","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T10:59:12Z","timestamp":1620817152000},"page":"1180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Adipose-Derived Mesenchymal Stromal Cells Treated with Interleukin 1 Beta Produced Chondro-Protective Vesicles Able to Fast Penetrate in Cartilage"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1800-3424","authenticated-orcid":false,"given":"Alessandra","family":"Colombini","sequence":"first","affiliation":[{"name":"Laboratorio di Biotecnologie Applicate all\u2019Ortopedia, IRCCS Istituto Ortopedico Galeazzi, I-20161 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0272-7417","authenticated-orcid":false,"given":"Enrico","family":"Ragni","sequence":"additional","affiliation":[{"name":"Laboratorio di Biotecnologie Applicate all\u2019Ortopedia, IRCCS Istituto Ortopedico Galeazzi, I-20161 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Mortati","sequence":"additional","affiliation":[{"name":"INRIM-Istituto Nazionale di Ricerca Metrologica, 10135 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0750-0505","authenticated-orcid":false,"given":"Francesca","family":"Libonati","sequence":"additional","affiliation":[{"name":"Laboratorio di Biotecnologie Applicate all\u2019Ortopedia, IRCCS Istituto Ortopedico Galeazzi, I-20161 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-8668","authenticated-orcid":false,"given":"Carlotta","family":"Perucca Orfei","sequence":"additional","affiliation":[{"name":"Laboratorio di Biotecnologie Applicate all\u2019Ortopedia, IRCCS Istituto Ortopedico Galeazzi, I-20161 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6463-6564","authenticated-orcid":false,"given":"Marco","family":"Vigan\u00f2","sequence":"additional","affiliation":[{"name":"Laboratorio di Biotecnologie Applicate all\u2019Ortopedia, IRCCS Istituto Ortopedico Galeazzi, I-20161 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Brayda-Bruno","sequence":"additional","affiliation":[{"name":"III Spine Surgery-Scoliosis Department, IRCCS Istituto Ortopedico Galeazzi, 20161 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9979-3092","authenticated-orcid":false,"given":"Laura","family":"de Girolamo","sequence":"additional","affiliation":[{"name":"Laboratorio di Biotecnologie Applicate all\u2019Ortopedia, IRCCS Istituto Ortopedico Galeazzi, I-20161 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: A disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1007\/s00167-018-5118-9","article-title":"Injective mesenchymal stem cell-based treatments for knee os-teoarthritis: From mechanisms of action to current clinical evidences","volume":"27","author":"Lopa","year":"2019","journal-title":"Knee Surg. 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