Concise Review: Patient-Derived Olfactory Stem Cells: New Models for Brain Diseases§

Authors

  • Alan Mackay-Sim

    Corresponding author
    1. National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland, Australia
    • National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland 4111, Australia
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  • Author contribution: Alan Mackay-Sim conceived, wrote and edited the manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS September 7, 2012.

Abstract

Traditional models of brain diseases have had limited success in driving candidate drugs into successful clinical translation. This has resulted in large international pharmaceutical companies moving out of neuroscience research. Cells are not brains, obviously, but new patient-derived stem models have the potential to elucidate cell biological aspects of brain diseases that are not present in worm, fly, or rodent models, the work horses of disease investigations and drug discovery. Neural stem cells are present in the olfactory mucosa, the organ of smell in the nose. Patient-derived olfactory mucosa has demonstrated disease-associated differences in a variety of brain diseases and recently olfactory mucosa stem cells have been generated from patients with schizophrenia, Parkinson's disease, and familial dysautonomia. By comparison with cells from healthy controls, patient-derived olfactory mucosa stem cells show disease-specific alterations in gene expression and cell functions including: a shorter cell cycle and faster proliferation in schizophrenia, oxidative stress in Parkinson's disease, and altered cell migration in familial dysautonomia. Olfactory stem cell cultures thus reveal patient-control differences, even in complex genetic diseases such as schizophrenia and Parkinson's disease, indicating that multiple genes of small effect can converge on shared cell signaling pathways to present as a disease-specific cellular phenotype. Olfactory mucosa stem cells can be maintained in homogeneous cultures that allow robust and repeatable multiwell assays suitable for screening libraries of drug candidate molecules. STEM CELLS2012;30:2361–2365

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