Efficient Serum-Free Derivation of Oligodendrocyte Precursors from Neural Stem Cell-Enriched Cultures§

Authors

  • Rajesh C. Rao,

    1. Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    2. Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, Maryland, USA
    3. Yale University School of Medicine, New Haven, Connecticut 06510, USA
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  • Justin Boyd,

    1. Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
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  • Raji Padmanabhan,

    1. Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
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  • Josh G. Chenoweth,

    1. Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
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  • Ronald D. McKay

    Corresponding author
    1. Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    • 35 Convent Drive, MSC 4092, Bethesda, Maryland 20892, USA
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    • Telephone: 301-496-6574


  • Author contributions: R.C.R.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; J.B., R.P., J.G.C.: collection and assembly of data, data analysis and interpretation; R.D.M.: Conception and design, financial support, manuscript writing, final approval of manuscript.

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

  • §

    First published online in STEM CELLSExpress April 10, 2008.

Abstract

Oligodendrocytes derived in the laboratory from stem cells have been proposed as a treatment for acute and chronic injury to the central nervous system. Platelet-derived growth factor (PDGF) receptor α (PDGFRα) signaling is known to regulate oligodendrocyte precursor cell numbers both during development and adulthood. Here, we analyze the effects of PDGFRα signaling on central nervous system (CNS) stem cell-enriched cultures. We find that AC133 selection for CNS progenitors acutely isolated from the fetal cortex enriches for PDGF-AA-responsive cells. PDGF-AA treatment of fibroblast growth factor 2-expanded CNS stem cell-enriched cultures increases nestin+ cell number, viability, proliferation, and glycolytic rate. We show that a brief exposure to PDGF-AA rapidly and efficiently permits the derivation of O4+ oligodendrocyte-lineage cells from CNS stem cell-enriched cultures. The derivation of oligodendrocyte-lineage cells demonstrated here may support the effective use of stem cells in understanding fate choice mechanisms and the development of new therapies targeting this cell type. STEM CELLS2009;27:116–125

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