Abstract
Dental mesenchymal stromal cells (MSCs) are multipotent cells present in dental tissues, characterized by plastic adherence in culture and specific surface markers (CD105, CD73, CD90, STRO-1, CD106, and CD146), common to all other MSC subtypes. Dental pulp, periodontal ligament, apical papilla, human exfoliated deciduous teeth, alveolar bone, dental follicle, tooth germ, and gingiva are all different sources for isolation and expansion of MSCs. Dental MSCs have regenerative and immunomodulatory properties; they are scarcely immunogenic but actively modulate T cell reactivity. in vitro studies and animal models of autoimmune diseases have provided evidence for the suppressive effects of dental MSCs on peripheral blood mononuclear cell proliferation, clearance of apoptotic cells, and promotion of a shift in the Treg/Th17 cell ratio. Appropriately stimulated MSCs produce anti-inflammatory mediators, such as transforming growth factor-β (TGF-β), prostaglandin E2, and interleukin (IL)-10. A particular mechanism through which MSCs exert their immunomodulatory action is via the production of extracellular vesicles containing such anti-inflammatory mediators. Recent studies demonstrated MSC-mediated inhibitory effects both on monocytes and activated macrophages, promoting their polarization to an anti-inflammatory M2-phenotype. A growing number of trials focusing on MSCs to treat autoimmune and inflammatory conditions are ongoing, but very few use dental tissue as a cellular source. Recent results suggest that dental MSCs are a promising therapeutic tool for immune-mediated disorders. However, the exact mechanisms responsible for dental MSC-mediated immunosuppression remain to be clarified, and impairment of dental MSCs immunosuppressive function in inflammatory conditions and aging must be assessed before considering autologous MSCs or their secreted vesicles for therapeutic purposes.
Highlights
Mesenchymal stromal cells (MSCs) are a subset of multipotent cells present in tissues of mesenchymal origin, mainly responsible for their regeneration
In 2006, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy defined three minimal criteria for MSCs: plastic adherence, ability to differentiate into chondroblasts, osteoblasts, and adipocytes in vitro, and the presence of several specific surface markers, such as CD105, CD73, and CD90 [1]
MSCs in general have been deeply investigated for their interactions with other immune cells, with the majority of data coming from bone marrow MSCs [59]
Summary
Mesenchymal stromal cells (MSCs) are a subset of multipotent cells present in tissues of mesenchymal origin, mainly responsible for their regeneration. With regard to dental tissue-derived MSCs, eight different subsets of MSCs have been identified so far: dental-pulp MSCs (DPMSCs), periodontal-ligament MSCs (PDLMSCs), MSCs from apical papilla (MSCAPs), MSCs from human exfoliated deciduous teeth (MSCHEDTs), alveolar bone-derived MSCs (ABMSCs), dental follicle progenitor cells (DFPCs), tooth germ progenitor cells (TGPCs), and gingival MSCs (GMSCs) [18,19,20]. Dental pulp MSCs (DPMSCs), MSCs from human exfoliated deciduous teeth (MSCHEDTs), periodontal ligament MSCs (PDLMSCs), alveolar-bone derived MSCs (ABMSCs), gingival MSCs (GMSCs), MSCs from apical papilla (MSCAPs), dental follicle progenitor cells (DFPCs), and tooth germ progenitor cells (TGPCs). MSCs are demonstrated to promote the proliferation of CD4+ CD25+ FOXP3+ Tregs both in vitro and in vivo [69,70,71] Those data have not entirely been confirmed for dental MSCs, it is possible to hypothesize similar mechanisms underlying their immunomodulatory action. MSCs in general have been deeply investigated for their interactions with other immune cells, with the majority of data coming from bone marrow MSCs [59]
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