Mesenchymal stem cell-based tissue regeneration therapies for periodontitis

Abstract

Periodontitis is commonly observed and is an important concern in dental health. It is characterized by a multifactorial etiology, including imbalance of oral microbiota, mechanical stress, and systemic diseases such as diabetes mellitus. The current standard treatments for periodontitis include elimination of the microbial pathogen and application of biomaterials for treating bone defects. However, the periodontal tissue regeneration via a process consistent with the natural tissue formation process has not yet been achieved. Developmental biology studies state that periodontal tissue is composed of neural crest-derived ectomesenchyme. To elucidate the process of periodontal regeneration, it is essential to understand the developmental background and intercellular cross-talk. Several recent studies have reported the efficacy of transplantation of mesenchymal stem cells for periodontal tissue regeneration. In this review, we discuss the basic knowledge of periodontal tissue regeneration using mesenchymal stem cells and highlight the potential of stem cell-based periodontal regenerative medicine.

Keywords: BMMSCs, bone marrow MSCs; BMP, bone morphogenetic protein; C-MSCs, clumps of MSC/ECM complexes; DFSCs, dental follicle stem cells; ECM, extracellular matrix; FGF, fibroblast growth factor; GDF-5, growth/differentiation factor-5; HERS, Hertwig epithelial root sheath; IFN-γ, interferon-gamma; IGFBP-6, insulin-like growth factor binding protein-6; LepR, leptin receptor; MSCs, mesenchymal stem cells; Mesenchymal stem cells; NCCs, neural crest cells; PDGFRα, platelet derived growth factor receptor α; PDL, periodontal ligament; PDLSCs, periodontal ligament stem cells; Periodontal tissue; Periodontitis; Pluripotent stem cells; TNF-α, tumor necrosis factor-alpha; Tissue regeneration; Wnt, wingless-INT; iPSC-MSCs, iPSC-derived MSCs; iPSCs, induced pluripotent stem cells; scRNA-seq, single-cell RNA sequence.