Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists

Abstract

Adult mesenchymal stem cells (MSCs) have recently become a potent tool in regenerative medicine. Due to certain shortcomings of obtaining bone marrow MSCs, alternate sources of MSCs have been sought. In this work, we studied MSCs from dental pulp (DP-MSCs) and dental follicle (DF-MSCs), isolated from the same tooth/donor, to define differences in their phenotypic properties, differentiation potential, and immunomodulatory activities. Both cell types showed colony-forming ability and expressed typical MSCs markers, but differed in the levels of their expression. DF-MSCs proliferated faster, contained cells larger in diameter, exhibited a higher potential to form adipocytes and a lower potential to form chondrocytes and osteoblasts, compared with DP-MSCs. In contrast to DF-MSCs, DP-MSCs produced the transforming growth factor (TGF)-β and suppressed proliferation of peripheral blood mononuclear cells, which could be neutralized with anti-TGF-β antibody. The treatment with toll-like receptor 3 (TLR3) agonist augmented the suppressive potential of both cell types and potentiated TGF-β and interleukin-6 secretions by these cells. TLR4 agonist augmented the suppressive potential of DF-MSCs and increased TGF-β production, but abrogated the immunosuppressive activity of DP-MSCs by inhibiting TGF-β production and the expression of indolamine-2,3-dioxygenase-1. Some of these effects correlated with the higher expression of TLR3 and TLR4 by DP-MSCs compared with DF-MSCs. When transplanted in imunocompetent xenogenic host, both cell types induced formation of granulomatous tissue. In conclusion, our results suggest that dental MSCs are functionally different and each of these functions should be further explored in vivo before their specific biomedical applications.

Osteogenic potential of periodontal ligament stem cells are unaffected after exposure to lipopolysaccharides

“…This low expression of STRO-1 is in agreement with other reports in PDLSCs, 27 PDL cells, 28 dental pulp and dental follicle stem cells. 29 After exposure to bacterial toxin, on average 0.71% of PDLSCs remained positive for STRO-1. Stem cell markers expression showed that there was no significant difference in exposed versus non-exposed cells, however it is important to highlight the distinct behavior of each PDLSC population.…”

Isolation, Characterization and Comparative Differentiation of Human Dental Pulp Stem Cells Derived from Permanent Teeth by Using Two Different Methods

“…[1][2][3][4][5][6][7][8]17,18 DPSCs are identified by their negative expression of hematopoietic antigens (e.g., CD45, CD34, CD14), and positive expression of CD90, CD29, CD73, CD105, CD44 and STRO-1. 19,20 Easy obtained potential with minimum pain & morbidity make human DPSCs as a valuable source of MSCs compared to the ordinary sources, such as bone marrow mesenchymal stem cells 21 . In general, DPSCs have been isolated by either outgrowth method, i.e., migration of stem cells from pulp tissue explants (DPSC-OG) [22][23][24] , and/or by enzymatic digestion (DPSC-ED) 4,6,25 .…”

Mesenchymal Stem Cells from Periapical Lesions Upregulate the Production of Immunoregulatory Cytokines by Inflammatory Cells in Culture / Mezenhimske matične ćelije iz periapeksnih lezija stimulišu produkciju imunoregulacijskih citokina od strane inflamacijskih ćelija u kulturi

“…It can be postulated that this cytokine is important for down-regulation of inflammatory and immune responses within PLs and for the repair of periapical bone loss. PL-MSCs, like other dental MSCs, also produce TGF-β (12,13). In our co-culture model, the number of PL-MSCs was significantly lower than the number of PL-ICs (1:10, respectively), therefore the contribution of TGF-β produced by PL-MSCs in the co-culture, could be considered as less important.…”

“…Except for their substantial differentiation capacity and low immunogenicity, it was demonstrated that different MSCs, including our PL-MSCs lines, have profound anti-proliferative and anti-inflammatory effects (9,12,13). Since the production of proinflammatory cytokines is controlled by the immunoregulatory cytokines, the principal aim of this study was to check the involvement of PL-MSCs in these processes.…”

“…The flow cytometry was used for characterization of a clone after the fourth passage, as previously described (12,13) leukocyte antigen (HLA)-DR-phycoerithryne (PE), and mouse IgG1a negative control-PE were also from Serotec. The indirect labelling was performed using anti-STRO-1 (Millipore/Chemicon) mAb followed by secondary anti-mouse IgG1-FITC mAb.…”