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PERIODONTITIS THERAPY USING COMBINED IMPLANTATION OF AUTOLOGOUS ADIPOSE-DERIVED STROMAL CELLS AND PLATELET LYSATE-BASED HYDROGEL: A DOUBLE-BLIND RANDOMIZED CONTROLLED PRECLINICAL STUDY IN A SPONTANEOUS CANINE MODEL
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Edité par CCSD -
International audience. Background & Aim: Periodontitis is a dysbiotic chronic inflammatory age-related disease of the periodontium, leading to the destruction of the tooth-supporting tissues. At the present time, current therapies give insufficient and unpredictable results, and long-term basis restoration of periodontal tissue homeostasis leading to tissue regeneration remains a challenge. Given their significant pro-angiogenic, anti-bacterial and immuno-modulatory capabilities, adipose-derived stromal cells (ASCs) graft within a suitable vehicle, may be proposed to achieve this aim. Methods, Results & Conclusion: 15 beagle dogs (mean age 9.6 ± 2.5 years) with spontaneous periodontitis were included in a double-blind split-mouth study with random affectation of the treatment per mandibular side. After non- surgical periodontal treatment, mandibular periodontal lesions were grafted with a platelet lysate-based hydrogel with or without autologous ASCs. Clinical examination and X-rays were used to assess periodontal tissue loss severity (periodon- tal pocket depth (PPD) and clinical attachment level (CAL)) and in- flammatory activity (bleeding on probing (BoP), gingival index (GI)) of periodontal sites at 45 and 120 days after grafting. Histological analysis was also carried at 120 days. RNA-sequencing (RNA-seq) was performed to identify ASC expression profile and putative association with clinical outcomes. Although inter-individual heterogeneity, all clinical parameters of both disease severity and activity were improved at 120 days in ASC grafted sites compared to hydrogel alone treated sites. The mean difference adjusted on the subject and the baseline value (aMD [CI95%]) highlighted a significant clinical improvement at 120 days (PPD:-1.24[-1.64;- 0.85]; p<0.001; CAL:-1.16[- 1.80;-0.53]; p<0.001; BoP: -0.60[-0.85;-0.36]; p<0.001; GI: -0.37[-0;52;-0.22]; p<0.001), confirmed by X-ray imaging data. Microscopic analysis demonstrated more stabilized periodontium in ASC grafted sites than controls. Finally, RNA-seq data pointed out different gene expression profiles related to CAL and BoP improvement. This double-blind randomized clinical trial performed on spontaneous lesions developed in the older dog shows for the first time autologous ASC therapy as relevant to induce a stable periodontal regeneration, thus opening opportunities for innovative regenerative periodontal therapies.
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