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Imaging-based chemical screens using normal and glioma-derived neural stem cells

Danovi, Davide ; Falk, Anna LU ; Humphreys, Peter ; Vickers, Richard ; Tinsley, Jon ; Smith, Austin G and Pollard, Steven M (2010) In Biochemical Society Transactions 38(4). p.71-1067
Abstract

The development of optimal culture methods for embryonic, tissue and cancer stem cells is a critical foundation for their application in drug screening. We previously described defined adherent culture conditions that enable expansion of human radial glia-like fetal NS (neural stem) cells as stable cell lines. Similar protocols proved effective in the establishment of tumour-initiating stem cell lines from the human brain tumour glioblastoma multiforme, which we termed GNS (glioma NS) cells. Others have also recently derived more primitive human NS cell lines with greater neuronal subtype differentiation potential than NS cells, which have similarities to the early neuroepithelium, named NES (neuroepithelial stem) cells. In the present... (More)

The development of optimal culture methods for embryonic, tissue and cancer stem cells is a critical foundation for their application in drug screening. We previously described defined adherent culture conditions that enable expansion of human radial glia-like fetal NS (neural stem) cells as stable cell lines. Similar protocols proved effective in the establishment of tumour-initiating stem cell lines from the human brain tumour glioblastoma multiforme, which we termed GNS (glioma NS) cells. Others have also recently derived more primitive human NS cell lines with greater neuronal subtype differentiation potential than NS cells, which have similarities to the early neuroepithelium, named NES (neuroepithelial stem) cells. In the present paper, we discuss the utility of these cells for chemical screening, and describe methods for a simple high-content live-image-based platform. We report the effects of a panel of 160 kinase inhibitors (Inhibitor Select I and II; Calbiochem) on NES cells, identifying three inhibitors of ROCK (Rho-associated kinase) as promoting the expansion of NES cell cultures. For the GNS cells, we screened a panel of 1000 compounds and confirmed our previous finding of a cytotoxic effect of modulators of neurotransmitter signalling pathways. These studies provide a framework for future higher-throughput screens.

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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diagnostic Imaging/methods, Glioma/diagnosis, High-Throughput Screening Assays/methods, Humans, Models, Biological, Neoplastic Stem Cells/drug effects, Neurons/drug effects, Small Molecule Libraries/analysis, Stem Cells/drug effects
in
Biochemical Society Transactions
volume
38
issue
4
pages
5 pages
publisher
Biochemical Society
external identifiers
  • scopus:77955956233
  • pmid:20659005
ISSN
0300-5127
DOI
10.1042/BST0381067
language
English
LU publication?
no
id
950bd6ee-9318-4b76-a87c-b21329508318
date added to LUP
2021-08-10 13:45:12
date last changed
2024-02-04 01:34:06
@article{950bd6ee-9318-4b76-a87c-b21329508318,
  abstract     = {{<p>The development of optimal culture methods for embryonic, tissue and cancer stem cells is a critical foundation for their application in drug screening. We previously described defined adherent culture conditions that enable expansion of human radial glia-like fetal NS (neural stem) cells as stable cell lines. Similar protocols proved effective in the establishment of tumour-initiating stem cell lines from the human brain tumour glioblastoma multiforme, which we termed GNS (glioma NS) cells. Others have also recently derived more primitive human NS cell lines with greater neuronal subtype differentiation potential than NS cells, which have similarities to the early neuroepithelium, named NES (neuroepithelial stem) cells. In the present paper, we discuss the utility of these cells for chemical screening, and describe methods for a simple high-content live-image-based platform. We report the effects of a panel of 160 kinase inhibitors (Inhibitor Select I and II; Calbiochem) on NES cells, identifying three inhibitors of ROCK (Rho-associated kinase) as promoting the expansion of NES cell cultures. For the GNS cells, we screened a panel of 1000 compounds and confirmed our previous finding of a cytotoxic effect of modulators of neurotransmitter signalling pathways. These studies provide a framework for future higher-throughput screens.</p>}},
  author       = {{Danovi, Davide and Falk, Anna and Humphreys, Peter and Vickers, Richard and Tinsley, Jon and Smith, Austin G and Pollard, Steven M}},
  issn         = {{0300-5127}},
  keywords     = {{Diagnostic Imaging/methods; Glioma/diagnosis; High-Throughput Screening Assays/methods; Humans; Models, Biological; Neoplastic Stem Cells/drug effects; Neurons/drug effects; Small Molecule Libraries/analysis; Stem Cells/drug effects}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{71--1067}},
  publisher    = {{Biochemical Society}},
  series       = {{Biochemical Society Transactions}},
  title        = {{Imaging-based chemical screens using normal and glioma-derived neural stem cells}},
  url          = {{http://dx.doi.org/10.1042/BST0381067}},
  doi          = {{10.1042/BST0381067}},
  volume       = {{38}},
  year         = {{2010}},
}