title: High content screening of defined chemical libraries using normal and glioma-derived neural stem cell lines.
abstract: Small molecules with potent biological effects on the fate of normal and cancer-derived stem cells represent both useful research tools and new drug leads for regenerative medicine and oncology. Long-term expansion of mouse and human neural stem cells is possible using adherent monolayer culture. These cultures represent a useful cellular resource to carry out image-based high content screening of small chemical libraries. Improvements in automated microscopy, desktop computational power, and freely available image processing tools, now means that such chemical screens are realistic to undertake in individual academic laboratories. Here we outline a cost effective and versatile time lapse imaging strategy suitable for chemical screening. Protocols are described for the handling and screening of human fetal Neural Stem (NS) cell lines and their malignant counterparts, Glioblastoma-derived neural stem cells (GNS). We focus on identification of cytostatic and cytotoxic "hits" and discuss future possibilities and challenges for extending this approach to assay lineage commitment and differentiation.
authors.affiliation: Department of Cancer Biology, UCL Cancer Institute, University College London, London, United Kingdom.
authors.forename: Davide
authors.initials: D
authors.lastname: Danovi
authors.forename: Amos A
authors.initials: AA
authors.lastname: Folarin
authors.forename: Bart
authors.initials: B
authors.lastname: Baranowski
authors.forename: Steven M
authors.initials: SM
authors.lastname: Pollard
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000191:economics / Q000379:methods*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D057166:High-Throughput Screening Assays / Q000191:economics / Q000379:methods; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D054852:Small Molecule Libraries