Abstract

Neural stem cells (NSCs) provide promising approaches for investigating embryonic neurogenesis, modeling of the pathogenesis of diseases of the central nervous system, and for designing drug-screening systems. Such cells also have an application in regenerative medicine. The most convenient and acceptable source of NSCs is pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells). However, there are many different protocols for the induction and differentiation of NSCs, and these result in a wide range of neural cell types. This review is intended to summarize the knowledge accumulated, to date, by workers in this field. It should be particularly useful for researchers who are beginning investigations in this area of cell biology.

Highlights

  • The in vitro generation of neural stem cells (NSCs) is a very attractive direction in terms of studying the processes of neural induction and the differentiation of progenitors into different types of neurons

  • The development of NSC generation protocols has been continuing for a substantial time

  • There are many different protocols that differ in the conditions and duration required for cultivation

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Summary

INTRODUCTION

The in vitro generation of neural stem cells (NSCs) is a very attractive direction in terms of studying the processes of neural induction and the differentiation of progenitors into different types of neurons. Later it turned out that RA causes differentiation into neural cells with caudal specification and blocks the differentiation of neurons of the central part of the CNS (Wichterle et al, 2002) Based on this default-like mechanism of neural tissue formation, Tropepe et al (2001) obtained floating spheres (neurospheres) of primitive NSCs from single ESCs of mice (mESCs), on chemically defined serum-free medium, feeder layer-free, in low-density culture conditions, in the presence of leukemia inhibitory factor (LIF) and FGF-2. After a 5-day exposure of the hPSCs to Noggin/SB431542, the cells became a Sox1-, Pax6- and ZIC1-positive early neuroepithelial population capable of neural rosette organization (Chambers et al, 2009) This protocol showed an 80% efficiency of hESC and hiPSC differentiation into Pax6-positive NSCs. The combination of Dual-SMAD-inhibition with the SDIA and SFEB methods was used by Morizane et al (2011). This method allowed the generation of cerebral organoids with vascular structures, without inhibiting neuronal differentiation (Ham et al, 2020)

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