Functional Differentiation of Neural Stem Cells into Neuronal Subtypes: A Biological Tool for Developmental Neurotoxicity Studies

Ankita Pandey,Madhulika Singh

doi:10.18311/jeoh/2018/17925

Abstract

Neural Stem Cells (NSCs), owing to their potential to get differentiated into various mature cell subtypes including neuronal cells have proved to be an indefinite source of 'raw material' for their application in developmental neurotoxicity as well as therapeutic intervention in neurodegenerative disorders. However, applications of NSCs for such purposes have been broadly limited by lack of enough methods for their directed differentiation. Herein, we describe a chemically defined protocol for efficient differentiation of rat neural stem cells to neuronal subtypes using an 8-day time period. NSCs, subject to NGF (50 ng/mL) were differentiated into neuronal sub-types supplemented with a cocktail of growth factors and supplements. Differentiating cells revealed a gradual and significant induction in the neuronal markers and a parallel decrease in markers of stemness as confirmed by immunocytochemical and translational analysis. The expression of markers was found to be maximum at day 8 of differentiation. Such selective differentiation of NSCs into neurons could offer an imperative step towards generation of NSC derivatives that could facilitate their utilization for research studies.

Highlights

Therapeutic application of Neural Stem Cells (NSCs) differentiation into neurons for tissue transplantation studies has been a significant hallmark of stem cell research
The efficient differentiation of NSCs has raised the possibility that it may provide a novel source of neuronal cells for nervous tissue replacement or repair after injury or neurodegeneration[2]
In 1992 NSCs were isolated from the striatum of adult mice and grown in the presence of Epidermal Growth Factor (EGF)

Summary

Introduction

Therapeutic application of NSC differentiation into neurons for tissue transplantation studies has been a significant hallmark of stem cell research. With capabilities of differentiating into neurons, oligodendrocytes and astrocytes, NSCs, serve as a promising tool for the treatment of many acquired and hereditary diseases of CNS1. Their application has been extended to elucidate the toxic effects of a variety of environmental contaminants. The efficient differentiation of NSCs has raised the possibility that it may provide a novel source of neuronal cells for nervous tissue replacement or repair after injury or neurodegeneration[2]. Post EGF removal, cells could differentiate and express markers of neural or glial origin, an indication of stem cells in the adult brain6.) These findings gave birth to a very useful in vitro model to understand cell fate determination

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