Enhancing the expression of neurotrophic factors in epidermal neural crest stem cells by valproic acid: A potential candidate for combinatorial treatment

Abstract

Effective delivery of trophic factors to cure neurological disorders and traumatic injuries is a major challenge. With promising therapeutic effects of epidermal neural crest stem cells (EPI-NCSCs) in preclinical spinal cord injury, there is an implication that these stem cells might provide supportive role through releasing various trophic agents. Hence, the present study was designed to assess the influence of valproic acid (VPA), a well-known histone deacetylases inhibitor, on mRNA expression of selected trophic factors. In this study, following stem cell migration from explanted hair bulges, immunostaining against Nestin, SOX-10, DCX, β-III tubulin and GFAP was carried out. Then, cells were treated with various clinically relevant concentrations of VPA and the survival rate was defined by MTT assay. Finally, stem cells were treated with 0.1 and 1 mM VPA and the drug impact on the transcription level of BDNF, GDNF, VEGF, NGF and NT3 at 6, 24, 72, 168 h was assessed by quantitative real-time PCR. The examined proteins expressions in the population of migrated cells confirmed the identity of stem cells as EPI-NCSCs. In addition, MTT assay showed that all three tested concentrations of VPA were suitable to treat these cells. Trophic factors assessment, following treatment revealed the mRNA expression level of BDNF, GDNF and VEGF could be significantly up- regulated at various time points, mainly by 1 mM VPA. However, NGF and NT3 transcripts were enhanced at few limited time points. Our findings showed that EPI-NCSCs due to secretion of various trophic factors are potential candidate to deliver the required trophic agents and their potential can be enhanced by 1 mM VPA, predominantly following 168 h treatment. Hence, these cells can be utilized to modulate destructive context of neurological disorders and injuries.