Immunomodulating Profile of Dental Mesenchymal Stromal Cells: A Comprehensive Overview

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.

Combined Transcriptomic and Protein Array Cytokine Profiling of Human Stem Cells from Dental Apical Papilla Modulated by Oral Bacteria

“…Stem cells interact with their niche, establishing a dynamic system that determines cell and tissue fate [28]. In the root canal, the presence of bacteria, as well as their residuals and toxins, is likely to impact the biology of SCAP and interfere with the success of regenerative endodontic treatments.…”

A New Target of Dental Pulp-Derived Stem Cell-Based Therapy on Recipient Bone Marrow Niche in Systemic Lupus Erythematosus

“…Apoptotic hDPSCs show immunosuppressive efficacy in vivo [ 37 ], suggesting that the apoptotic phenomena of donor hDPSCs and recipient T lymphocytes contribute to this efficacy. hDPSCs can also release multiple paracrine factors to regulate the proliferation and differentiation of T lymphocytes [ 38 ]. We summarized the molecules involved in the immunosuppressive function of hDPSCs ( Table 1 ).…”

“…However, the therapeutic action of singly transplanted hDPSCs seems to be mediated in recipient MRL/ lpr mice via indirect communication through donor hDPSC-derived bioactive trophic factors and EVs rather than by direct communication with T lymphocytes. Recent studies have shown that hDPSCs can secrete various cytokines and chemokines with anti-inflammatory and anti-fibrogenic activities in the conditioned medium of hDPSCs (hDPSC-CM) [ 38 ]. Multiple administrations of hDPSC-CM containing multiple soluble factors have multiple effects on recipients with acute and chronic inflammation and autoimmune diseases [ 38 ].…”

“…Recent studies have shown that hDPSCs can secrete various cytokines and chemokines with anti-inflammatory and anti-fibrogenic activities in the conditioned medium of hDPSCs (hDPSC-CM) [ 38 ]. Multiple administrations of hDPSC-CM containing multiple soluble factors have multiple effects on recipients with acute and chronic inflammation and autoimmune diseases [ 38 ]. However, the immunosuppressive mechanism of singly transplanted donor hDPSCs cannot be exploited by multiple administrations of hDPSC-CMs.…”

A Review of Antimicrobial Activity of Dental Mesenchymal Stromal Cells: Is There Any Potential?

“…Similar to MSCs from bone marrow and other tissues, dental MSCs exhibit immunomodulatory properties and can influence the activity of almost all types of immune cells [14,57,58]. The immunomodulatory ability of dental MSCs is strongly upregulated by various inflammatory cytokines and some Tolllike receptors [14,58].…”