Abstract
BackgroundPulpitis is a common dental disease characterized by sustained inflammation and impaired pulp self-repair. Mesenchymal stem cell-based minimally invasive vital pulp therapy (MSC-miVPT) is a potential treatment method, but its application is limited by the difficulty in acquiring MSCs. We recently revealed the immunomodulatory effects of rat dental follicle stem cells (rDFSCs) on acute lung injury. The present study focused on the paracrine effects of rDFSCs on the inflammation and regeneration of rat injured dental pulp to detect whether DFSCs are a potential candidate for MSC-miVPT.MethodsConditioned medium from rDFSCs (rDFSC-CM) was applied to lipopolysaccharide (LPS)-induced inflammatory rat dental pulp cells (rDPCs). The inflammation and regeneration of rDPCs were detected by RT-qPCR, Western blotting, immunofluorescence staining, Cell Counting Kit-8 (CCK-8) assay, flow cytometry, wound-healing assay, and Masson’s staining. The effects of rDFSC-CM on inflamed rat dental pulp were further evaluated by hematoxylin-eosin and immunohistochemical staining.ResultsrDFSC-CM downregulated the ERK1/2 and NF-κB signaling pathways, which resulted in suppression of the expression of IL-1β, IL-6, and TNF-α and promotion of the expression of IL-4 and TGF-β, and these findings lead to the attenuation of rDPC inflammation. rDFSC-CM enhanced the in vitro proliferation, migration, and odontogenic differentiation of inflammatory rDPCs and their in vivo ectopic dentinogenesis. Furthermore, rDFSC-CM inhibited inflammatory cell infiltration in rat pulpitis and triggered Runx2 expression in some of the odontoblast-like cells surrounding the injured site, and these effects were conducive to the repair of inflamed dental pulp.ConclusionsrDFSC-CM exhibits therapeutic potential by rescuing the regeneration of the inflamed rat dental pulp through an immunomodulatory mechanism, indicating the application prospects of DFSCs in biological regenerative endodontics.
Highlights
Pulpitis is a common dental disease characterized by sustained inflammation and impaired pulp selfrepair
Identification of rat dental follicle stem cells (rDFSCs) and rat dental pulp cells (rDPCs) DFSCs and rDPCs were successfully isolated from rat dental follicle or dental pulp tissues (Fig. 1a, f), and immunofluorescence analysis showed that rDFSCs and rDPCs were both positive for the Mesenchymal stem cells (MSCs) marker vimentin (Fig. 1b, g) and negative for the epithelial marker cytokeratin (Fig. 1c, h)
After induction in osteogenic medium for 14 days, both rDFSCs and rDPCs formed mineralized nodules that were visualized by Alizarin Red staining (Fig. 1d, i)
Summary
Pulpitis is a common dental disease characterized by sustained inflammation and impaired pulp selfrepair. MSCs exert immunosuppressive effects by suppressing the secretion of proinflammatory factors while increasing the expression of anti-inflammatory mediators of immune cells [9, 10], and on the other hand, MSCs regulate immune responses by eliciting the reprogramming of macrophages, suppressing the activation of B and T cells, and facilitating the proliferation of Treg cells [6, 7, 11, 12] Based on their immunomodulatory capacities, MSCs are prospective candidates for use in cellbased therapies for various immune and inflammatory diseases [13,14,15], but the application of these therapies is limited by difficulty in acquiring MSCs
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