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The significant contribution of the inflammatory response to periodontitis occurrence and development has been extensively documented. Although the efficacy of treatments based on mesenchymal stromal cells (MSCs) has been proved, that of na\u00efve MSCs treatment remains suboptimal. Herein, human MSCs stably expressing interleukin\u201010 (IL\u201010\u2010MSCs) were established and evaluated for their performance in treating ligature\u2010induced periodontitis rats. Utilising the electroporation method, a recombinant plasmid containing the human IL10 gene was introduced into human MSCs derived from umbilical cord to generate IL\u201010\u2010MSCs. These IL\u201010\u2010MSCs and blank vector transfected MSCs were transplanted into rat ligature\u2010induced periodontitis models by repeated injections via the periodontal and tail veins. Following MSCs transplantation, their therapeutic effects on the rat model and the underlying mechanisms were explored. IL\u201010\u2010MSCs injections markedly promoted periodontal tissue regeneration, decreased bone resorption, and inhibited inflammation at the lesion area, relative to transplantation with unmodified MSCs as a control. Additionally, treatment with IL\u201010\u2010MSCs respectively enhanced and decreased the proportions of macrophages undergoing alternative (M2) and classical (M1) activation at the lesion site. IL\u201010\u2010MSCs exhibited more promising therapeutic efficacy against periodontitis in rats than naive MSCs and might represent a novel periodontitis treatment option.<\/jats:p>","DOI":"10.1111\/jcmm.70934","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T20:19:59Z","timestamp":1762201199000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Interleukin\u201010 Modified Human Mesenchymal Stromal Cells Markedly Alleviated Periodontitis by Inducing Macrophage\n                    <scp>M2<\/scp>\n                    Polarisation"],"prefix":"10.1111","volume":"29","author":[{"given":"Aerali","family":"Heinayati","sequence":"first","affiliation":[{"name":"Department of Stomatology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Fuyang People's Hospital Anhui Medical University  Fuyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyun","family":"Gao","sequence":"additional","affiliation":[{"name":"Clinical Stem Cell Center, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liudi","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Stem Cell Center, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Stem Cell Center, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2978-1061","authenticated-orcid":false,"given":"Haiyan","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.18-0006"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8060537"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.18-0181"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00379"},{"issue":"5","key":"e_1_2_13_6_1","article-title":"Exploring the Potential of Micro\u2010Immunotherapy in the Treatment of Periodontitis","volume":"14","author":"Ferra\u2010Canellas M. 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