Lipoxin A4 and Resolvin D1 Preserve Neural Inductive Capacity of Dental Pulp Stem Cells Cultured Under Inflammatory Conditions.

Human dental pulp stem cells (DPSCs) exhibit neurogenic differentiation potential; however, inflammatory conditions may impair this process. This study investigated the impact of tumor necrosis factor alpha (TNF-α) on the neurodifferentiation potential of DPSCs and the modulatory role of the pro-resolving lipid mediators lipoxin A4 (LXA4) and resolvin D1 (RvD1). DPSCs were isolated and subjected to neuronal differentiation for 21 days. Cells were treated with different concentrations of TNF-α (1, 10, 25, and 100 ng/mL) and with LXA4 or RvD1 (10 and 100 nM). After 21 days, neuronal differentiation was associated with a reduction in the stem cell marker OCT3/4 (53% in the absence of TNF-α and 48.5% in the presence of TNF-α) and increased expression of the early neuronal marker doublecortin (87% in the absence of TNF-α and 116% in the presence of TNF-α). The intermediate neuronal marker βIII-tubulin increased by 135% in the absence of TNF-α but decreased by 40% in its presence. The reduction in βIII-tubulin induced by 25 ng/mL TNF-α was partially attenuated by treatment with 100 nM RvD1 (p = 0.02) or 10 nM LXA4 (p = 0.02). These findings suggest that LXA4 and RvD1 help preserve the neural differentiation potential of DPSCs cultured under inflammatory conditions.