Immunomodulating Profile of Dental Mesenchymal Stromal Cells: A Comprehensive Overview

Dental mesenchymal stromal cells (MSCs) are multipotent cells present in dental tissues, characterized by plastic adherence in culture and by specific surface markers (CD105, CD73,CD90, STRO-1, CD106 and CD146), common to all other MSCs 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 as well as immunomodulatory properties; they are scarcely immunogenic, but actively modulate T cell reactivity. invitro studies and animal models of autoimmune diseases have provided evidence for the suppressive effects of dental MSCs on PBMC 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 TGF-β, PGE2 and 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 MSCs-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 for the treatment of 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 MSCs-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.