Periodontitis therapy using autologous adipose-derived stromal cells: a double-blind randomized controlled clinical trial in an aged canine model

• Published in: Cytotherapy (Oxford, England) England), 2024-11
• Main Authors: Monsarrat, Paul, Laurencin-Dalicieux, Sara, Jourdan, Géraldine, Blasco-Baque, Vincent, Bourdens, Marion, Bouhsira, Emilie, Cecchin-Albertoni, Chiara, Conchou, Fabrice, Loubières, Pascale, Minty, Matthieu, Arnaud, Emmanuelle, Dupuis-Coronas, Sophie, Guissard, Christophe, Chaumont, Jade, Casteilla, Louis, Raymond-Letron, Isabelle, Planat-Bénard, Valérie, Kemoun, Philippe
• Format: Article
• Language: English
• Subjects: cell therapy; mesenchymal stromal cells, naturally-occurring disease model; periodontal regeneration; pre-clinical model
• ISSN: 1465-3249
• DOI: 10.1016/j.jcyt.2024.10.012

The aim of this randomized double-blind trial was to assess the biosafety and efficacy of cell therapy by adipose-derived stromal cells (ASC) in a suitable hydrogel biomaterial to improve clinical and biological outcomes in a canine model of spontaneous periodontitis. 16 elderly beagle dogs with spontaneous periodontitis were included in a double-blind split-mouth design. After non-surgical periodontal treatment, mandibular lesions were randomly grafted with a platelet lysate-based hydrogel with or without autologous ASC. Clinical and biological examination assessed the severity of periodontal tissue loss, inflammatory activity and subgingival microbiota initially and at 45 and 120 days (4 dogs) after grafting. Histological analyses were also carried out at 120days. RNA-sequencing was performed to identify ASC expression fingerprint of clinical improvement. The adjusted mean difference (aMD[CI95%]) highlighted a significant improvement of tissue gain and inflammation reduction at 120days (periodontal pocket depth: -1.24mm[-1.64;-0.85]; clinical attachment level CAL: -1.16mm[-1.80;-0.53]; gingival index: -0.37 score[-0.52;-0.22]), together with a decrease of periopathogenic subgingival microbiota. Microscopic analysis demonstrated more stabilized periodontium in ASC grafted sites than controls. RNA-sequencing pointed out different gene expression profiles related to CAL improvement. Despite inter-individual heterogeneity, clinical parameters related to both disease severity and activity were improved at 120days in ASC grafted sites compared to hydrogel alone treated sites. This pre-clinical study confirms the effectiveness of autologous ASC for periodontitis treatment in a highly relevant pathophysiological canine model. Results provide compelling evidence of a notable restoration of periodontal tissue equilibrium and robust recovery. [Display omitted]