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  • Patient-derived stem cells: pathways to drug discovery for brain diseases

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    Author(s)
    Mackay-Sim, Alan
    Griffith University Author(s)
    Mackay-Sim, Alan
    Year published
    2013
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    Abstract
    The concept of drug discovery through stem cell biology is based on technological developments whose genesis is now coincident. The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS). The second is patient-derived stem cells for modeling the cell biology of brain diseases. HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs. HCS combines new fluorescent probes with automated microscopy and computational power to quantify the effects ...
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    The concept of drug discovery through stem cell biology is based on technological developments whose genesis is now coincident. The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS). The second is patient-derived stem cells for modeling the cell biology of brain diseases. HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs. HCS combines new fluorescent probes with automated microscopy and computational power to quantify the effects of compounds on cell functions. Stem cell biology has advanced greatly since the discovery of genetic reprograming of somatic cells into induced pluripotent stem cells (iPSCs). There is now a rush of papers describing their generation from patients with various diseases of the nervous system. Although the majority of these have been genetic diseases, iPSCs have been generated from patients with complex diseases (schizophrenia and sporadic Parkinson's disease). Some genetic diseases are also modeled in embryonic stem cells (ESCs) generated from blastocysts rejected during in vitro fertilization. Neural stem cells have been isolated from post-mortem brain of Alzheimer's patients and neural stem cells generated from biopsies of the olfactory organ of patients is another approach. These "olfactory neurosphere-derived" cells demonstrate robust disease-specific phenotypes in patients with schizophrenia and Parkinson's disease. HCS is already in use to find small molecules for the generation and differentiation of ESCs and iPSCs. The challenges for using stem cells for drug discovery are to develop robust stem cell culture methods that meet the rigorous requirements for repeatable, consistent quantities of defined cell types at the industrial scale necessary for HCS.
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    Journal Title
    Frontiers in Cellular Neuroscience
    Volume
    7
    DOI
    https://doi.org/10.3389/fncel.2013.00029
    Copyright Statement
    © The Author(s) 2013. The attached file is reproduced here in accordance with the copyright policy of the publisher. For information about this journal please refer to the journal’s website or contact the authors.
    Subject
    Biochemistry and cell biology
    Neurosciences
    Neurology and neuromuscular diseases
    Publication URI
    http://hdl.handle.net/10072/56964
    Collection
    • Journal articles

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