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

Abstract

The aim of this randomized double-blind trial was to assess the biosafety and efficacy of cell therapy by adipose-derived stromal cells (ASCs) in a suitable hydrogel biomaterial to improve clinical and biological outcomes in a canine model of spontaneous periodontitis. A total of 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 ASCs. Clinical and biological examination assessed the severity of periodontal tissue loss, inflammatory activity and subgingival microbiota initially and at 45 days and 120 days (four dogs) after grafting. Histological analyses were also carried out at 120 days. RNA sequencing was performed to identify the ASC expression fingerprint of clinical improvement. The adjusted mean difference (95% confidence interval) highlighted a significant improvement in tissue gain and inflammation reduction at 120 days (periodontal pocket depth, -1.24 mm [-1.64, -0.85], clinical attachment level, -1.16 mm [-1.80, -0.53], Gingival Index, -0.37 [-0.52, -0.22]) together with a decrease in 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 clinical attachment level improvement. Despite inter-individual heterogeneity, clinical parameters related to both disease severity and activity were improved at 120 days in ASC-grafted sites compared with sites treated with hydrogel alone. This pre-clinical study confirms the effectiveness of autologous ASCs 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.