Lipoxina A4 e Resolvina D1 preservam a capacidade de indução neural de células-tronco da polpa dentária cultivadas sob condições inflamatórias

Abstract

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 DPSC neurodifferentiation 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. The optimal TNF-α concentration was determined in a pilot study using real-time PCR. The expression of OCT3/4, doublecortin, and β-III-tubulin was analyzed by MTT assay, flow cytometry, and immunofluorescence. The effects of LXA4 (10 or 100 nM) and RvD1 (10 or 100 nM) were assessed by flow cytometry. Data were analyzed using the Kruskal–Wallis test followed by the Mann–Whitney test (p<0.05) and one-way ANOVA with Tukey’s post hoc test. TNF-α at a concentration of 25 ng/mL was shown to induce inflammation without causing cytotoxicity. The high production of doublecortin indicated the neuronal differentiation potential of DPSCs, whereas reduced β-III-tubulin expression demonstrated that TNF-α inhibits the progression of neuronal differentiation. Conversely, increased β-III-tubulin expression in the presence of LXA4 (10 and 100 nM; p=0.02 and p=0.03, respectively) and RvD1 (100 nM; p=0.02) indicate that these mediators attenuate the inhibitory effects of TNF-α. These findings suggest that anti-inflammatory therapy combined with DPSCs may enhance motor recovery following neurotrauma.