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Patients received either conventional therapy with hyaluronic acid (HA) alone (Control group, <jats:italic>n<\/jats:italic>\u2009=\u200911) or in combination with hP-MSCs (MSC group, <jats:italic>n<\/jats:italic>\u2009=\u200915) via three intra-articular injections with 4-week intervals. Clinical outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Scale (VAS), and magnetic resonance imaging (MRI) at 6 and 12 months following the first injection. Blood samples were analyzed for cytokine levels.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Three injections of hP-MSCs combined with HA were well-tolerated, with no severe adverse events observed. Significant improvements in WOMAC and VAS scores were noted in the MSC group compared to the Control group at both 6 and 12 months. MRI analysis revealed no significant differences in cartilage thickness or optical density index between the groups. Additionally, serum cytokine analysis showed a significant decrease in interleukin-2 (IL-2) levels in the MSC group, indicating an anti-inflammatory effect of hP-MSCs. However, no significant changes were observed in other cytokines.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This study demonstrates that three intra-articular injections of cryopreserved hP-MSCs in combination with HA are safe and effective for treating KOA, providing sustained clinical improvement at the 1-year follow-up.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial registration<\/jats:title>\n            <jats:p>NCT04453111, #7\/09.26.2018. Registered 02 January 2020, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04453111\" ext-link-type=\"uri\">https:\/\/www.clinicaltrials.gov\/study\/NCT04453111<\/jats:ext-link>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12891-025-08664-2","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T00:47:54Z","timestamp":1745628474000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effectiveness and safety of multiple injections of human placenta-derived MSCs for knee osteoarthritis: a nonrandomized phase I trial"],"prefix":"10.1186","volume":"26","author":[{"given":"Yevhen","family":"Holiuk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Birsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetiana","family":"Bukreieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petro","family":"Nemtinov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitalii","family":"Kyryk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Ustymenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadym","family":"Mazevych","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mykola","family":"Sokolov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galyna","family":"Lobyntseva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volodymyr","family":"Shablii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,26]]},"reference":[{"key":"8664_CR1","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","volume":"396","author":"C Abbafati","year":"2020","unstructured":"Abbafati C, Abbas KM, Abbasi M, Abbasifard M, Abbasi-Kangevari M, Abbastabar H, et al. 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