Combination of EPI-NCSCs and DMF Improves Their Potential Therapeutic Functions by Upregulation of Expression of Neurotrophic Factors; In vivo Study

Background and Aim: Stem cell therapy has been considered as a newmodulation in the treatment of neurologic diseases. Epidermal neuralcrest stem cells (EPI-NCSCs) are multipotent stem cells which are presentin the bulge of the adult hair follicle and their therapeutic functionshave been reported. Dimethyl fumarate (DMF), which has been usedin the treatment of multiple sclerosis is newly introduced as effectiveneuroprotective therapy in stroke models. In the current study, weevaluated the effect of DMF on the relative expression of trophic factorsin EPI-NCSCs and their potential therapeutic benefits.Methods: The bulge of adult rat hair follicles were placed onto thecollagen coated cell culture plate and after EPI-NCSCs migration, cellswere detached. Verification of expanded EPI-NCSCs was performed usingimmunofluorescent staining. To determine the appropriate concentrationof DMF for EPI-NCSCs treatment, the MTT assay was employed andbased on acquired data, EPI-NCSCs treated with 10μM DMF for 6, 24,72 or 168 hours. In each time point, the quantitative RT-PCR techniquewas used to evaluate transcripts of NGF and VEGF.Results: The acquired data showed that 10μM DMF significantlyincreased the mRNA expression of NGF 72 hours following treatment;however the inhibitory effect of DMF on GDNF mRNA expression wasobserved in various time points.Conclusion: Our findings revealed that DMF up-regulated one of themajor neurotrophic factors in the epidermal neural crest stem cells.Therefore, the combination of EPI-NCSCs therapy with DMF treatmentmight be a valuable strategy to improve their potential therapeuticfunctions in vivo.

Keywords:

Dimethyl fumarate , Epidermal neural crest stem cell , Trophic factors , Gene expression