Biomedical Engineering Reference
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demonstrating a variable thickness in its layering and cell density, depending
upon the region along the anterior-posterior extent of the lateral ventricular
system. In general, four layers to the adult human SVZ can be identified: the
inner most layer, a monolayer of ependymal cells lining the ventricular cavity
(layer I); a hypocellular gap (layer II) abutting the ependymal layer; a ribbon of
astrocytes, some of which may function as neural stem cells (layer III); and a
transitional zone (layer IV) into the overlying brain parenchyma. Using both
immunohistochemical and ultrastructural analyses, oligodendrocytes have also
been observed in the astrocyte ribbon of layer III, a layer which only exists
along the lateral ventricles and not along the third ventricle, fourth ventricle, or
the medial (septal) wall in humans.
3 Glial Progenitors in the Subcortical White Matter
Beyond the ventricular and subventricular zones, a loosely organized popula-
tion of glial progenitors accounts for 2% of the adult rat white matter and as
many as 4% of the adult human subcortical white matter (Assanah et al. 2006;
Nunes et al. 2003). Although these cells are typically non-migratory and slowly
proliferating in vivo (Roy et al. 1999; Noble et al. 1992), in vitro studies have
shown that adult glial progenitors can be induced to become more migratory
and proliferative when treated with growth factors including PDGF, EGF,
FGF, and glial growth factor (Wolswijk et al. 1991; Wolswijk and Noble
1992; Shih and Holland 2006). Using flow-cytometry techniques, these cells
can also be extracted and identified on the basis of their expression of an
immature neural ganglioside recognized by monoclonal antibody A2B5
(Nunes et al. 2003). They do not, however, express more mature glial markers
and in vitro can be induced to function as neural stem cells in the presence of
exogenous growth factors. Subcortical white matter glial progenitors serve an
unknown function in the adult human brain, but represent a large source of
parenchymal progenitors that could be involved in gliomagenesis, or even serve
as a possible cell-of-origin for some gliomas. Unfortunately, very little is known
about the lineage relationships of these cells, their putative microenvironment,
or their relationship to the subventricular zone.
4 Emergence of the Cancer Stem Cell Hypothesis
Germinal regions such as the subventricular zone have long been suspected as a
possible source of gliomas (Vick et al. 1977; Lantos and Cox 1976). Not
surprisingly, many gliomas are either periventricular or contiguous with the
ventricular or subventricular zone (Lim et al. 2007) and contain cells possessing
phenotypic and behavioral characteristics shared by neural stem cells. Features
common to both progenitor cells and gliomas include high motility, potential to
