Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

3.3 Glioma Culture Systems Introduction
ploidy observed in late passage serum cells. In addition, loss of the
wild-type p53 allele in late passage serum cells leaves only the mutant
p53 allele found in both the NBE cells and the parental tumours, caus-
ing a well-known genomic instability [130,153]. These genomic changes
further demonstrate the significant differences between serum cells and
their matched parental tumours [261].
In conclusion, by using a model system derived from primary glioblastomas,
Lee et al [261] have demonstrated that NBE-cultured cells derived from pri-
mary glioblastomas bear remarkable similarity to normal NS cells by retaining
the ability to form neurospheres in vitro; an indefinite self-renewal potential;
the ability to differentiate into the glial and neuronal lineages of the CNS; hav-
ing gene expression profiles similar to NS cells; bearing genetic stability over
many passages in vitro; harbour all of the genetic aberrations found within
the primary tumour; have gene expression profiles similar to the glioblastomas
they were derived from; appear to be the principal tumourigenic cell type that
can recapitulate the overall in vivo phenotype of the parental glioblastoma.
By contrast, cells derived from the same glioblastoma specimens but grown in
serum-containing media lose all the characteristics of primary tumour cultures,
although they ultimately regain the tumourigenic potential in later passages
without being able to recapitulate the tumourigenic phenotype of the original
tumour however, but rather matching the phenotypic and genotypic patterns
found in most glioma cell lines.
Since several groups have reported that tumour stem cell-like cells can be
isolated from the established tumour cell lines by culture in serum-free me-
dia with selected growth factors [242,385], experiments need to be carried out
to validate how these cells maintain their tumour stem cell-like properties in
differentiation-inducing conditions and if cells with stem-like properties may
emerge again through epigenetic reprogramming or selection of a subpopula-
tion of cells with genomic instability.
Based on their findings, Lee et al propose that the inherent tumour stem cell
population within primary glioblastomas is quickly lost in typical glioma cul-
ture conditions, and the cells found following prolonged in vitro passages are
the product of an outgrowth of a cell clone that has undergone profound de
novo genetic and/or epigenetic changes. This indicates that NBE cells may
be an optimal model system for understanding the biology of primary human
tumours, for the preclinical screening of agents and to guide personalized tu-
mour therapy. The table 3.1 below summarises the findings of this study [261].
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