Dental Pulp-Derived Stem Cells Reduce Inflammation, Accelerate Wound Healing and Mediate M2 Polarization of Myeloid Cells.

Abstract

This work aimed to validate the potential use of dental pulp-derived stem cells (DPSCs) for the treatment of inflammation by defining their mechanisms of action. We planned to investigate whether priming of DPSC with proinflammatory molecules had any impact on their behavior and function. In the first step of our validation in vitro, we showed that priming of DPSCs with the bioactive agents LPS, TNF-α, or IFN-γ altered DPSCs' immunologic properties by increasing their expression levels of IL-10, HGF, IDO, and IL-4 and by decreasing their mitochondrial functions. Moreover, DPSCs induced accelerated wound healing irrespective of priming, as determined by using a gut epithelial cell line in a scratch wound assay. Wound healing of gut epithelial cells was mediated by regulating the expressions of AKT, NF-κB, and ERK1/2 proteins compared to the control epithelial cells. In addition, primed DPSCs altered monocyte polarization toward an immuno-suppressive phenotype (M2), where monocytes expressed higher levels of IL-4R, IL-6, Arg1, and YM-1 compared to monocytes cultured with control DPSCs. In silico analysis revealed that this was accomplished in part by the interaction between kynurenine and PPARγ, which regulated the expression of M2 differentiation-related genes. Collectively, these data provided evidence that the DPSCs reduced inflammation, induced M2 polarization of myeloid cells, and healed damaged gut epithelial cells through inactivation of inflammation and modulating constitutively active signaling pathways.