Application of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets for Periodontal Regeneration

Periodontitis is a chronic inflammatory disorder that causes destruction of the periodontal attachment apparatus including alveolar bone, the periodontal ligament, and cementum. Dental implants have been routinely installed after extraction of periodontitis-affected teeth; however, recent studies have indicated that many dental implants are affected by peri-implantitis, which progresses rapidly because of the failure of the immune system. Therefore, there is a renewed focus on periodontal regeneration aroundnatural teeth. To regenerate periodontal tissue, many researchers and clinicians have attempted to perform periodontal regenerative therapy using materials such as bioresorbable scaffolds, growth factors, and cells. The concept of guided tissue regeneration, by which endogenous periodontal ligament- and alveolar bone-derived cells are preferentially proliferated by barrier membranes, has proved effective, and various kinds of membranes are now commercially available. Clinical studies have shown the significance of barrier membranes for periodontal regeneration; however, the technique is indicated only for relatively small infrabony defects. Cytokine therapies have also been introduced to promote periodontal regeneration, but the indications are also for small size defects. To overcome this limitation, ex vivo expanded multipotent mesenchymal stromal cells (MSCs) have been studied. In particular, periodontal ligament-derived multipotent mesenchymal stromal cells are thought to be a responsible cell source, based on both translational and clinical studies. In this review, responsible cell sources for periodontal regeneration and their clinical applications are summarized. In addition, recent transplantation strategies and perspectives about the cytotherapeutic use of stem cells for periodontal regeneration are discussed.