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Cell-based tissue engineering is a promising alternative for periodontal regeneration as current therapies fail to reconstitute tissue damage caused by periodontitis. As newly identified postnatal stem cells, gingiva-derived mesenchymal stem cells (GMSCs) have been focused on for isolation and expansion in vitro of cells with multi-differentiation potential and immunomodulatory capacities. It has been demonstrated that systemically delivered GMSCs can home to the mandibular bone defect sites and promote bone regeneration. However, the role of transplanted GMSCs in the treatment of periodontitis has not been reported. In the present study, GMSCs were transplanted into C57BL/6J mice with periodontitis via the tail vein to investigate the contribution of GMSCs to periodontal tissue regeneration. Results demonstrated that the alveolar bone heights of mice with transplanted GMSCs were significantly increased compared with the control groups and GMSCs were detected in newly formed periodontal ligament and alveolar bone. The results of the present study implied that systemically transplanted GMSCs could home to periodontal injury sites and promote periodontal tissue regeneration.