Human glioma-derived neuronal stem cell lines as a model for drug screening
These adherent glioma neural stem (GNS) cell lines retain the characteristics of the original tumour-initiating cells, delivering a powerful model system for chemical and genetic screening.
In vitro model to study cell transformation and tumourogenicity
The most common and aggressive type of adult brain cancer is malignant glioma. Current treatments for these cancers are largely ineffective. Establishing cell lines from tumours that retain cancer-initiating stem cell properties would provide a valuable and accurate model of the human disease. Prior attempts to purify and propagate GNS cell lines in vitro have been unsuccessful resulting in the formation of spheres that are limited by: generation of short lived progenitor cells, spontaneous differentiation, cell death and heterogeneity. Additionally, real-time monitoring is not possible.
University of Edinburgh researchers have shown that cancer stem cells can be isolated from diverse adult and childhood brain tumours and grown as adherent cultures. Uniform access to growth factors suppresses differentiation, enabling expansion of highly pure and stable populations of stem cells. Unlike cellular spheres, these cell lines can be used to develop screening assays to identify potential therapeutics or genetic markers for diagnosis and to improve selection of appropriate therapeutic regimes for patients with brain tumours.
Our findings indicate that gliomas are not driven by a single phenotype of tumour cell type. For example, G144 is indicative of an oligodendrocyte precursor cell, whereas G179 is more representative of adult SVZ astrocytes. Moreover, a live cell imaging-based chemical screen using 450 FDA approved drugs identified both differential sensitivities of GNS cells and a common susceptibility to perturbation of serotonin signalling illustrating the utility and scalability of adherent GNS cell lines for screening purposes. Additionally, these cells lines are demonstrated as useful for real-time genetic and morphometric screening using fluorescent reporters.
- Homogenous exposure to nutrients, oxygen and growth factors
- Versatile and renewal resource of cells
- Accurate model of human disease suitable for (high-throughput) chemical and genetic screening
Pollard et al, Cell Stem Cell (2009), 4: 568–580