LAUSR

INTRODUCTION Melatonin is an endogenous neurohormone with well-reported anti-inflammatory and anti-oxidant properties, but the direct biological and immunomodulatory effects of melatonin on human dental pulp stem cells (hDPSCs) has not been fully elucidated. AIM To evaluate the influence of melatonin on the cytocompatibility, proliferation, cell migration, odontogenic differentiation, mineralized nodule formation and immunomodulatory properties of human DPSCs (hDPSCs). METHODS To address the melatonin biological effects on hDPSCs, the cytocompatibility, proliferation, cell migration, odontogenic differentiation, mineralized nodule formation and immunomodulatory properties of human hDPSCs after melatonin treatment were evaluated. The statistical differences were evaluated using one-way ANOVA with Tukey's multiple-comparisons test. RESULTS It was found that melatonin did not alter hDPSC immunophenotype or cell viability, even at the highest concentrations used. However, using intermediate melatonin concentrations (10-300 μM), a significantly higher proliferation rate (*P<.05, **P<.01) and migration of hDPSCs (**P<.01) were observed. Importantly, melatonin treatment (100 μM) significantly increased the secretion of the anti-inflammatory cytokine TGFβ (*P<.05, **P<.01) and provokes a more robust anti-proliferative effect on mitogen-stimulated T cells (*P<.05). Finally, and unlike previous results found with MSCs from other sources, melatonin fails to induce or to accelerate the spontaneous osteogenic differentiation of hDPSCs. CONCLUSIONS Together, these findings provide key data on the bioactivity of melatonin and its effects on hPDSC biological and immunomodulatory properties. CLINICAL RELEVANCE Melatonin may be considered as a potential pre-activation agent of hDPSCs to be clinically used for attenuating inflammation by regulating an increased host immunoinflammatory response, and for promoting regeneration of the dentin-pulp tissues in different oral cavity affectations such as post-surgical wounds after tooth extractions, carious lesions or other oral traumatic injuries.