Abstract
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.
Highlights
Periodontal disease is mainly caused by oral bacteria
These results suggested that the conditioned medium of Periodontal Ligament (PDL)-mesenchymal stromal cells (MSCs) enhanced periodontal regeneration by suppressing the inflammatory response through tumor necrosis factor-α (TNF-α) production
Taking into account the concept of GTR, it is clear that the stem cells within the PDL tissue are the key cells for periodontal regeneration and homeostasis; the cytotherapeutic approach for periodontal regeneration has started with PDL-derived cells
Summary
Periodontal disease is mainly caused by oral bacteria. Without dental treatment, bacteria-induced inflammation can spread and destroy the periodontal ligament, alveolar bone, cementum, and gingiva. Because the MSCs used in each laboratory were different, the MSC Committee of the International Society of Cell Therapy (ISCT) published a statement paper in 2006 that defined the minimal criteria of human MSC characteristics, including the following: (1) adherence to plastic under standard culture conditions; (2) specific surface antigen expression (positive for CD105, CD73, and CD90; negative for CD45, CD34, CD14 or CD11b, CD79a or CD19, and HLA-DR); and (3) in vitro differentiation capacity into osteoblasts, adipocytes, and chondroblasts [5] These cells exhibit different characteristics in terms of proliferation ability, differentiation potential, and gene expression profiles, most of the cells possess additional characteristics, such as immunomodulatory properties, and the ability to mediate trophic factors [6]. PDL-MSCs express both osteoblastic and known periodontal marker genes, such as periostin and S100A4, when they are cultured in an osteoinductive medium, suggesting that osteoinductive pretreatment may enhance the ability of PDL-MSCs to induce periodontal regeneration
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