Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis

Abstract

Gingiva-Derived Mesenchymal Stromal Cells (GMSCs) have been shown to play an important role in periodontitis. However, how P. gingivalis, one of the key etiological agents of the disease, affects healthy (H)- and periodontitis (P)-GMSCs is unknown. To address this problem, we established 10 H-GMSC and 12 P-GMSC lines. No significant differences in morphology, differentiation into chondroblasts and adipocytes, expression of characteristic MSCS markers, including pericyte antigens NG2 and PDGFR, were observed between H- and P-GMSC lines. However, proliferation, cell size and osteogenic potential were higher in P-GMSCs, in contrast to their lower ability to suppress mononuclear cell proliferation. P. gingivalis up-regulated the mRNA expression of IL-6, IL-8, MCP-1, GRO-α, RANTES, TLR-2, HIF-1α, OPG, MMP-3, SDF-1, HGF and IP-10 in P-GMSCs, whereas only IL-6, MCP-1 and GRO-α were up-regulated in H-GMSCs. The expression of MCP-1, RANTES, IP-10 and HGF was significantly higher in P-GMSCs compared to H-GMSCs, but IDO1 was lower. No significant changes in the expression of TLR-3, TLR-4, TGF-β, LAP, IGFBP4 and TIMP-1 were observed in both types of GMSCs. In conclusion, our results suggest that P-GMSCs retain their pro-inflammatory properties in culture, exhibit lower immunosuppressive potential than their healthy counterparts, and impaired regeneration-associated gene induction in culture. All these functions are potentiated significantly by P. gingivalis treatment.

Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions

“…Cumulatively, our results showed that these GMSC lines are very similar to the lines that we had previously established [15] and, as such, were used for the curren experiments.…”

“…The staining of tissue sections with anti-CD146 mAb and anti-CD31 mAb (an endothelial marker) identified CD146 + CD31pericytes (Figure 1b). Cumulatively, our results showed that these GMSC lines are very similar to the lines that we had previously established [15] and, as such, were used for the current experiments.…”

“…They share many similarities with other dental MSCs, such as fibroblastoid morphology, adherence to plastic substrates, differentiation potential to other types of mesenchymal cells, and the expression of characteristic markers, including those found on pericytes [13,14]. However, GMSCs possess some characteristics different from the rest of dental MSCs, such as easy isolation, absence of spontaneous differentiation, additional neurogenic and epithelial differentiation potential due to gingival origin from the neural crest, and morphological, phenotypical, and telomerase stability after long-term cultures [14,15]. Some potential roles of GMSCs during periodontitis include hard and soft tissue repair, immunomodulatory properties, angiogenesis, and antibacterial effects [14,16].…”

“…In addition, a pomegranate extract and punicallagin exerted antioxidant properties on human gingival fibroblasts but inhibited their proliferation at higher concentrations [35]. We hypothesized that PoPEx differently modulates gene expression in GMSCs established from healthy (H) and periodontitis-affected gingiva (P) based on our previous findings that many functional properties of these lines are different inflammation [15]. Therefore, the main goal of this study was to investigate and compare the effect of different concentrations of PoPEx on the proliferation of H-and P-GMSCs and the expression of genes in these lines involved in the processes of inflammation, immunomodulation, tissue damage, and remodeling, proliferation, senescence, and osteoblastogenesis, under physiological and pathological conditions.…”

In Vitro Investigation of Gelatin/Polycaprolactone Nanofibers in Modulating Human Gingival Mesenchymal Stromal Cells

“…TGF-β1 is also involved in angiogenesis and serves as a pivotal immunosuppressive secreted polypeptide. Moreover, as a versatile growth factor, it governs various behaviors and functions of fibroblasts and MSCs, thereby orchestrating tissue remodeling by producing connective tissue constituent and matrix proteins [56]. In our study, both VEGF-A and TGF-β1 mRNA levels increased when cultured on GPP within a two-week period, whereas VSCM only showed significant effects after 7 days.…”