Neural stem cells and neuro‐oncology: Quo vadis?

Abstract

Conventionally, gliomas are assumed to arise via transformation of an intraparenchymal glial cell that forms a mass that then expands centrifugally, eventually invading surrounding tissues. We propose an alternative model in which gliomas arise via initiation and promotion of cells within the brain's subependymal layer or subventricular zone, the source of a recently characterized pool of neural cells with the properties of self-renewal and multipotentiality (i.e., stem cells) that persists into adulthood. In this model, the particular histological subtype of glioma would represent the effects of temporal and spatial environmental influences rather than the particular cell of origin and the disease's centrifugal point would be the subependymal layer. The implications of such a model are discussed.

Neural Progenitor Cell Lines Inhibit Rat Tumor Growth in Vivo

“…We found that HiB5 also inhibited the outgrowth of N32 glioma cells, but animals coinoculated with N25 and HiB5 had a rapid tumor progression showing no difference in survival compared with the control animals inoculated with N25 alone. We have no explanation at present as to why the observed inhibition of tumor growth seems to be dependent on the glioma model used, but many gliomas could be of neural progenitor origin themselves (36). This indicates the possibility that neural progenitor cells situated near or in direct contact with glioma cells could influence the proliferative potential and differentiation status of the glioma cells by signals originating from the differentiating neural progenitor cell line HiB5 or ST14A.…”

Unique expression and localization of aquaporin‐ 4 and aquaporin‐9 in murine and human neural stem cells and in their glial progeny

“…It would be interesting to investigate the potential correlation between AQP4 expression and the maintenance of an immature glial phenotype by adult astrocytes in vitro, also in view of the fact that adult SVZ stem cells have been shown to derive from radial glia (Merkle et al, 2004) and that putative stem cells have been described in the human adult brain that display glial morphology and antigenic properties (Sanai et al, 2004). These periventricular glia-like neural stem cells and their progeny might be implicated in the generation of brain tumors (Rubinstein et al, 1984;Recht et al, 2003), as well as in the process of endogenous brain repair (Fallon et al, 2000;Nakatomi et al, 2002). Thus, a better characterization of these cells in terms of their water homeostasis dynamics might be critical for the development of potential therapeutic approaches for CNS disorders.…”

Loss ofp53Induces Changes in the Behavior of Subventricular Zone Cells: Implication for the Genesis of Glial Tumors

“…Given their ability to proliferate, self-renew, and migrate, these cells have also the potential to undergo neoplastic transformation (Recht et al, 2003), and a large body of evidence supports this concept, although the identity of the transformed cells is not well defined (Rao, 1999;Holland, 2000;Berger et al, 2004;Jang et al, 2004). Four distinct cell types reside in the adult SVZ (Doetsch et al, 1997(Doetsch et al, , 1999a.…”

“…The importance of SVZ cells in the genesis of glioblastomas (Recht et al, 2003) has been suggested by the isolation of neurosphere-forming cells from human glioblastomas (Ignatova et al, 2002) and by studies on transgenic mice (Holland, 2000) and on animals prenatally exposed to the mutagen N-ethyl-Nnitrosourea (ENU) (Oda et al,1997;Leonard et al, 2001;Slikker et al, 2004;Savarese et al, 2005).…”