Distinctions between fetal and adult human platelet-derived growth factor–responsive neural precursors

Authors

  • Andrew Chojnacki PhD,

    1. Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • John J. P. Kelly MD,

    1. Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Walter Hader MD,

    1. Department of Clinical Neurosciences, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Samuel Weiss PhD

    Corresponding author
    1. Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    • Department of Cell Biology and Anatomy, 3330 Hospital Drive, NW, University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1
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Abstract

Objective

Platelet-derived growth factor (PDGF)–responsive neural precursors (PRPs; also known as oligodendrocyte progenitor cells) are one of the best characterized precursor cell populations of the rodent central nervous system. Yet little is known about the biology of human PRPs because of an apparent inability to culture and expand them in large numbers. This study was designed to establish an approach that allows direct comparisons between the biology of fetal and adult human PRPs, as a means to address potential differences in intrinsic myelin-production capabilities.

Methods

We used the neurosphere culture system, under low plating density, to isolate, culture, and compare the properties of fetal and adult human PRPs.

Results

PDGF stimulated fetal human PRPs to generate neurospheres that differentiated primarily into oligodendrocytes, which acquired myelin basic protein expression, as well as neurons and a small number of astrocytes. Together with PDGF, fibroblast growth factor 2 promoted fetal human PRP expansion. In contrast, adult human PRPs isolated from the corpus callosum required twice the culture period to generate neurospheres, which contained oligodendrocytes, as well as astrocytes, but not neurons. Strikingly, fibroblast growth factor 2 did not promote adult human PRP self-renewal.

Interpretation

Differences in the intrinsic proliferation, phenotype, and self-renewal properties of fetal and adult human PRPs suggest they are distinct populations, which may result in distinct myelin-production capabilities. Ann Neurol 2008;64:127–142

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