Mesenchymal Stem Cells of Dental Origin for Inducing Tissue Regeneration in Periodontitis: A Mini-Review

Abstract

Periodontitis is a chronic disease that begins with a period of inflammation of the supporting tissues of the teeth table and then progresses, destroying the tissues until loss of the teeth occurs. The restoration of the damaged dental support apparatus is an extremely complex process due to the regeneration of the cementum, the periodontal ligament, and the alveolar bone. Conventional treatment relies on synthetic materials that fill defects and replace lost dental tissue, but these approaches are not substitutes for a real regeneration of tissue. To address this, there are several approaches to tissue engineering for regenerative dentistry, among them, the use of stem cells. Mesenchymal stem cells (MSC) can be obtained from various sources of adult tissues, such as bone marrow, adipose tissue, skin, and tissues of the orofacial area. MSC of dental origin, such as those found in the bone marrow, have immunosuppressive and immunotolerant properties, multipotency, high proliferation rates, and the capacity for tissue repair. However, they are poorly used as sources of tissue for therapeutic purposes. Their accessibility makes them an attractive source of mesenchymal stem cells, so this review describes the field of dental stem cell research and proposes a potential mechanism involved in periodontal tissue regeneration induced by dental MSC.

Keywords: DPSC; biological mechanism; periodontal treatment.

Figure 1

Pathophysiological mechanisms in periodontitis. The presence of red complex bacteria promotes periodontal inflammation in susceptible individuals. Activated polymorphonuclear neutrophils (PMN), fibroblast, and monocytes in the oral cavity induce production of cytokines such as tumour necrosis factor α (TNF-α), interleukin (IL)-1, and IL-6. The initial function of this inflammation is to protect against bacteria; however, chronic inflammation induces enhanced reactive oxygen species (ROS), complement system, and PGE2 and matrix metalloproteinases (MMPs) such as gelatinase B and collagenase 1. This inflammatory microenvironment induces a Th1 lymphocyte profile, which promotes inflammation and is associated with the maintenance and progression of the lesion. In addition, activated monocytes induce cytokines as M-CSF (macrophage colony-stimulating factor) that promote activation and differentiation of osteoclasts, which are related to resorption of alveolar bone, damage to cementum, and periodontal ligament.

Figure 2

Characteristics of mesenchymal stem cells. The scheme shows the cellular differentiation capacity considering autoregeneration, replication, and differentiation in epithelial, neural, adipose, muscular, and sanguine cells.

Figure 3

Sources of stem cells in the human organism. The diagram shows some tissue sources of adult stem cells. (a) Peripheral blood, (b) Liver, (c) Bone marrow, (d) Muscles, (e) Skin, (f) Adipose tissue, (g) Dental tissues: (1. Apical dental papilla, 2. Adult pulp, 3. Pulp of deciduous teeth, 4. Periodontal ligament, and 5. Alveolar bone).

Figure 4

Putative mechanism involved in the regeneration of periodontal tissue via DP-MSCs. The placement of DP-MSCs allows the neoformation of blood vessels that carry signals (IL-6, IGF-1, and TNF-α andoncostatin M: OSM) and cells (Th2 and monocytes) to the site of the lesion. Signals, via the STAT3 and mTOR pathways, will allow the DP-MSCs to be transformed into osteoblasts, which in turn will produce ligands to bone morphogenic protein 2 (BMP), alkaline phosphatase (ALP), and runt-related transcription factor 2 (Runx2) for the generation of alveolar bone, whereas the production of IL-10 and osteoprotegerin (OPG) will create a suitable microenvironment in which osteoclast activity is inhibited and tissue repair is promoted. On the other hand, DP-MSCs also differentiate into cementoblasts and fibroblast, which secrete proteins such as CEMP1 and COL1 for synthesis of cementum and collagen fibres of the periodontal ligament, respectively. Finally, the neoformation of blood vessels, an environment with the indicated signals and the differentiation of DP-MSCs into the constituent cells of the periodontium, will jointly achieve the regeneration of periodontal tissues.PL: Periodontal ligament; Bmp: Bone morphogenic protein; RANKL: Receptor activator of nuclear factor kappa-Β ligand; NFATc1: Nuclear factor of activated T-cells, cytoplasmic 1; M-CSF: Macrophage colony-stimulating factor.