{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:13:35Z","timestamp":1791414815151,"version":"4.3.3"},"reference-count":123,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"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>Periodontitis is a common inflammatory disease that not only damages periodontal tissues but also induces systemic effects, including cardiac dysfunction. Mesenchymal stem cells (MSCs) offer regenerative potential due to their ability to differentiate, modulate immune responses, and secrete anti-inflammatory factors. However, the relative efficacy of local versus systemic MSC administration remains unclear. This study evaluated the therapeutic effects of adipose-derived MSCs (AD-MSCs) in a rat model of experimental periodontitis, comparing local and systemic administration. AD-MSCs were characterized based on morphology, surface marker expression, and differentiation potential. Ligature-induced periodontitis was established over 60 days, after which AD-MSCs (1 \u00d7 106 cells) were administered either supraperiosteally (local group) or intravenously (systemic group). Periodontal regeneration was assessed through clinical, radiographic, and histopathological analyses, while cardiac function was evaluated using echocardiography and histopathological examinations. Results demonstrated that local AD-MSC administration provided superior therapeutic benefits compared to systemic delivery. Locally administered cells significantly enhanced bone regeneration, reduced inflammation, and improved periodontal tissue architecture. In contrast, systemic administration offered moderate benefits but was less effective in restoring periodontal integrity. Similarly, in the heart, local treatment resulted in greater improvements in systolic function, as indicated by enhanced ejection fraction and fractional shortening, along with reduced myocardial fibrosis. Although systemic administration also provided cardioprotective effects, diastolic dysfunction persisted in both treatment groups. In conclusion, local AD-MSC administration proved more effective in regenerating periodontal tissues and mitigating cardiac dysfunction, highlighting its potential as an optimized therapeutic strategy for periodontitis and its systemic complications.<\/jats:p>","DOI":"10.3390\/ijms26093984","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T06:38:37Z","timestamp":1745390317000},"page":"3984","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Therapeutic Potential of Local and Systemic Adipose-Derived Mesenchymal Stem Cell Injections in a Rat Model of Experimental Periodontitis: Implications for Cardiac Function"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2362-5325","authenticated-orcid":false,"given":"Asmaa","family":"Elhaieg","sequence":"first","affiliation":[{"name":"Veterinary Teaching Hospital, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1953-4294","authenticated-orcid":false,"given":"Ahmed","family":"Farag","sequence":"additional","affiliation":[{"name":"Veterinary Teaching Hospital, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan"},{"name":"Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2732-0717","authenticated-orcid":false,"given":"Sai","family":"Koung Ngeun","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0660-7156","authenticated-orcid":false,"given":"Masahiro","family":"Kaneda","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Anatomy, Division of Animal Life Science, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimi","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Veterinary Teaching Hospital, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6256-4539","authenticated-orcid":false,"given":"Ahmed S.","family":"Mandour","sequence":"additional","affiliation":[{"name":"Department of Animal Medicine (Internal Medicine), Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9948-6490","authenticated-orcid":false,"given":"Ryou","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Veterinary Teaching Hospital, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/S0140-6736(05)67728-8","article-title":"Periodontal Diseases","volume":"366","author":"Pihlstrom","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1600-0757.2012.00443.x","article-title":"Clinical Utility of Stem Cells for Periodontal Regeneration","volume":"59","author":"Hynes","year":"2012","journal-title":"Periodontol. 2000"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1600-0757.2009.00303.x","article-title":"Stem Cells and Future Periodontal Regeneration","volume":"51","author":"Lin","year":"2009","journal-title":"Periodontol. 2000"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1089\/ten.teb.2009.0562","article-title":"Periodontal Tissue Engineering and Regeneration: Current Approaches and Expanding Opportunities","volume":"16","author":"Chen","year":"2010","journal-title":"Tissue Eng. 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