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Bioengineering of the Human Neural Stem Cell Niche: A Regulatory Environment for Cell Fate and Potential Target for Neurotoxicity

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Human Neural Stem Cells

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 66))

Abstract

Human neural stem/progenitor cells of the developing and adult organisms are surrounded by the microenvironment, so-called neurogenic niche. The developmental processes of stem cells, such as survival, proliferation, differentiation, and fate decisions, are controlled by the mutual interactions between cells and the niche components. Such interactions are tissue specific and determined by the biochemical and biophysical properties of the niche constituencies and the presence of other cell types. This dynamic approach of the stem cell niche, when translated into in vitro settings, requires building up “biomimetic” microenvironments resembling natural conditions, where the stem/progenitor cell is provided with diverse extracellular signals exerted by soluble and structural cues, mimicking those found in vivo. The neural stem cell niche is characterized by a unique composition of soluble components including neurotransmitters and trophic factors as well as insoluble extracellular matrix proteins and proteoglycans. Biotechnological innovations provide tools such as a new generation of tunable biomaterials capable of releasing specific signals in a spatially and temporally controlled manner, thus creating in vitro nature-like conditions and, when combined with stem cell-derived tissue specific progenitors, producing differentiated neuronal tissue structures. In addition, substantial progress has been made on the protocols to obtain stem cell-derived cell aggregates such as neurospheres and self-assembled organoids.

In this chapter, we have assessed the application of bioengineered human neural stem cell microenvironments to produce in vitro models of different levels of biological complexity for the efficient control of stem cell fate. Examples of biomaterial-supported two-dimensional and three-dimensional (2D and 3D) complex culture systems that provide artificial neural stem cell niches are discussed in the context of their application for basic research and neurotoxicity testing.

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Abbreviations

CNS:

Central nervous system

DNT:

Developmental neurotoxicity testing

ECM:

Extracellular matrix

ESC:

Embryonic stem cells

Fn:

Fibronectin

GFAP:

Glial fibrillary acidic protein

hESC:

Human embryonic stem cells

HUCB-NSC:

Human umbilical cord blood-derived neural stem cells

iPSC:

Induced pluripotent stem cells

Map-2:

Microtubule-associated protein-2

MAPK:

Mitogen-activated protein kinase

mdDA:

Midbrain dopaminergic

MEA:

Multielectrode array

MeHgCl:

Methylmercury chloride

NFA:

Network formation assay

NSC:

Neural stem cells

PDMS:

Polydimethylsiloxane

PEO-like:

Poly(ethylene) oxide-like

PI-3K:

Phosphoinositide-3-kinase

SGZ:

Subgranular zone

SVZ:

Subventricular zone

TH:

Tyrosine hydroxylase

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Acknowledgments

This work was sponsored by statutory funds to Mossakowski Medical Research Centre and Wroclaw Research Centre EIT+ under the project “Biotechnologies and advanced medical technologies”—BioMed (POIG.01.01.02-02-003/08) financed from the European Regional Development Fund (Operational Programme Innovative Economy, 1.1.2).

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Authors and Affiliations

  1. Stem Cell Bioengineering Unit, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

    Leonora Buzanska & Marzena Zychowicz

  2. European Commission, Joint Research Centre, Directorate for Health Consumers and Reference Materials, Ispra, Italy

    Agnieszka Kinsner-Ovaskainen

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  1. Leonora Buzanska
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  2. Marzena Zychowicz
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  3. Agnieszka Kinsner-Ovaskainen
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Correspondence to Leonora Buzanska .

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  1. Stem Cell Bioengineering Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

    Leonora Buzanska

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Buzanska, L., Zychowicz, M., Kinsner-Ovaskainen, A. (2018). Bioengineering of the Human Neural Stem Cell Niche: A Regulatory Environment for Cell Fate and Potential Target for Neurotoxicity. In: Buzanska, L. (eds) Human Neural Stem Cells. Results and Problems in Cell Differentiation, vol 66. Springer, Cham. https://doi.org/10.1007/978-3-319-93485-3_9

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