{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:05:37Z","timestamp":1789103137504,"version":"build-2803163510"},"reference-count":93,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Knee osteoarthritis (KOA) is a leading cause of pain and disability worldwide, and current treatments remain largely symptomatic, with no disease-modifying therapy established for routine use. This narrative review evaluates extracellular vesicles (EVs) as biological nanocarriers and a cell-free alternative to mesenchymal stromal cell therapy for KOA by examining the biological rationale, preclinical evidence, clinical studies, and current methodological and regulatory requirements. Preclinical findings indicate that EVs may exert immunomodulatory, anti-inflammatory, and chondroprotective effects, supporting their potential to influence joint homeostasis. The review also summarizes current recommendations for EV nomenclature, characterization, and quality control in accordance with the Minimal Information for Studies of EVs 2023 guidelines and highlights key translational challenges, including scalable manufacturing, potency assessment, and regulatory compliance. Clinical evidence to date suggests a favorable safety profile, but efficacy data remain limited and inconsistent; a randomized placebo-controlled trial showed no superiority over placebo, whereas small early human studies suggested possible benefit in selected cases. Overall, EVs represent a promising cell-free strategy for KOA, but current evidence is insufficient to support routine clinical use, emphasizing the need for standardized production, validated potency assays, and robust randomized clinical trials.<\/jats:p>","DOI":"10.3390\/ijms27093737","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:11:14Z","timestamp":1776931874000},"page":"3737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exosomes and Small Extracellular Vesicles as an Alternative to Mesenchymal Stromal Cell Therapy in Knee Osteoarthritis: From Biological Rationale to Clinical Evidence"],"prefix":"10.3390","volume":"27","author":[{"given":"Mahdi","family":"Al-Jeabory","sequence":"first","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, Silesian Center for Rheumatology, 43-450 Ustron, Poland"},{"name":"Clinical Department of Orthopedics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-800 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslaw","family":"Pecold","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, Ruda Slaska City Hospital, 41-793 Ruda Slaska, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0516-3231","authenticated-orcid":false,"given":"Maciej","family":"Maslyk","sequence":"additional","affiliation":[{"name":"Institute of Biological Science, The John Paul II Catholic University of Lublin, 20-950 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2140-9732","authenticated-orcid":false,"given":"Michal","family":"Pruc","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, The John Paul II Catholic University of Lublin, 20-950 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Gromek","sequence":"additional","affiliation":[{"name":"Institute of Biological Science, The John Paul II Catholic University of Lublin, 20-950 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Weglowski","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, The John Paul II Catholic University of Lublin, 20-950 Lublin, Poland"},{"name":"Clinical Department of Trauma and Orthopedic Surgery, The John Paul II Catholic University of Lublin, 21-300 Radzyn Podlaski, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0973-5455","authenticated-orcid":false,"given":"Lukasz","family":"Szarpak","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, The John Paul II Catholic University of Lublin, 20-950 Lublin, Poland"},{"name":"Henry J.N. Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1001\/jama.2020.22171","article-title":"Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review","volume":"325","author":"Katz","year":"2021","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chen, J., Chen, X., Wang, T., Li, M., Dai, H., Shang, S., Cheng, L., Tang, Z., Liu, S., and Huang, C. (2025). Global burden of knee osteoarthritis from 1990 to 2021: Trends, inequalities, and projections to 2035. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0320115"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Xie, X., Zhang, K., Li, Y., Li, Y., Li, X., Lin, Y., Huang, L., and Tian, G. (2025). 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