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Neural stem cell systems: physiological players or in vitro entities?

Nature Reviews Neuroscience volume 11, pages 176–187 (2010)Cite this article

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An Erratum to this article was published on 06 October 2010

Key Points

  • Neural stem cells (NSCs) are self-renewing multipotent populations present in the mammalian CNS. They generate the neurons and glia of the developing and adult brain.

  • During brain development, predetermined developmental programmes give rise to different NSC populations in specific locations and at specific times. This temporal development is partially recapitulated in vitro during embryonic stem cell neuralization processes.

  • Neurosphere- and monolayer-based protocols have allowed the isolation and growth of developmental stage-specific NSC populations in vitro.

  • Recent developments in monolayer NSC systems, devoid of any three-dimensional organization proper to the neurosphere structure, have allowed the generation of pure cultures of NSCs that can be stably maintained over passages, indicating that NSCs can divide and differentiate in vitro in the absence of any niche.

  • NSCs expanded in vitro can undergo deregulation of some of their original antigenic and biological properties (that is, their regional identity and differentiation potential). This alteration of the 'genuine' properties is induced by exposure to growth factors classically used for NSC growth (that is, epidermal growth factor and fibroblast growth factor 2).

Abstract

Neural stem cells (NSCs) can be experimentally derived or induced from different sources, and the NSC systems generated so far are promising tools for basic research and biomedical applications. However, no direct and thorough comparison of their biological and molecular properties or of their physiological relevance and possible relationship to endogenous NSCs has yet been carried out. Here we review the available information on different NSC systems and compare their properties. A better understanding of these systems will be crucial to control NSC fate and functional integration following transplantation and to make NSCs suitable for regenerative efforts following injury or disease.

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Figure 1: Developmental links between the different NSC populations that can be isolated or generated in vitro.
Figure 2: Sources of neurospheres and monolayer NSCs and results of differentiation.

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Acknowledgements

We apologize to colleagues for the omission of papers that could not be cited owing to space constraints. We thank G. Consalez and members of the laboratory for critical reading of the manuscript. The work of the authors is supported by EuroSystem (FP7, European Union Health-F4-2008-200720), ESTools (FP6, European Union LSHG-CT-2006-018739), NeuroStemcell (FP7, European Union HEALTH-2008-B-222943), Progetto Piattaforma Cariplo Nobel (Fondazione Cariplo, Italy; 20052042/104878) to E.C. and Progetto di Ricerca di Interesse Nazionale (MIUR, Italy; #20074MW29N) and Neuroscreen (FP6, European Union LSHB-CT-2007-037766) to L.C.

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  1. Department of Pharmacological Sciences and Center for Stem Cell Research, University of Milan, Via Balzaretti 9, Milano, 20133, Italy

    Luciano Conti & Elena Cattaneo

  2. Luciano Conti & Elena Cattaneo

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Glossary

Niche

A multicellular microenvironment supplying the factors required to maintain stem cell self-renewal and to direct their differentiation.

Antigenic

Pertaining to the expression of a specific marker or array of markers, specific parts of which are recognized by antibodies.

Neural plate

The thickened stripe of ectoderm overlying the notochord in early vertebrate embryos which contains cells that will give rise to the nervous system during embryonic development.

Neural tube

The cylindrical structure formed by the fusion of neural folds around the neural plate. The brain and spinal cord develop from the neural tube.

Rosette

Radial arrangements of columnar cells that express many of the proteins expressed in neuroepithelial cells in the neural tube. They are considered a developmental signature of neuroprogenitors in cultures of differentiating ESCs.

Clonal density

The density of cells (number of cells per l) that should allow formation of single-cell clones. Rigorously, clonality is assured solely by plating a single cell per well, thus allowing the investigation of properties of single cells. This step is essential for formal demonstration of self-renewal and potency.

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Conti, L., Cattaneo, E. Neural stem cell systems: physiological players or in vitro entities?. Nat Rev Neurosci 11, 176–187 (2010). https://doi.org/10.1038/nrn2761

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