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First published online November 21, 2007
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2007-0299v1
26/2/348    most recent
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Submitted on April 23, 2007
Accepted on November 13, 2007

TISSUE-SPECIFIC STEM CELLS

A High Concentration of Epidermal Growth Factor (EGF) Increases the Growth and Survival of Neurogenic Radial Glial Cells within Human Neurosphere Cultures

Aaron D. Nelson 1, Masatoshi Suzuki 1, Clive N. Svendsen 1*

1 Department of Anatomy & Neurology, University of Wisconsin-Madison, Neuroscience Training Program, University of Wisconsin-Madison, Waisman Center, University of Wisconsin-Madison

* To whom correspondence should be addressed. E-mail: svendsen{at}waisman.wisc.edu.


   Abstract

Human neural progenitor cells (hNPC) isolated from the fetal cortex can be expanded as aggregates of cells termed neurospheres. Traditional methods have used 20 ng/ml of epidermal growth factor (EGF) to drive the proliferation of these cells. Here we show that 100 ng/ml of EGF can significantly increase growth rates of hNPC at later passages. This was through increased survival of dividing cells rather than increased proliferation and associated with prolonged activation of ErbB2 and phosphorylated Akt. High EGF also resulted in a larger proportion of elongated "radial glial" like cells within the growing neurospheres and increased expression of the radial glial markers. The number of new neurons generated from cultures maintained in 100ng/ml EGF was significantly higher than from 20ng/ml EGF. Thus, high concentrations of EGF increase the survival of a highly neurogenic human radial glial cell.

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A. Nelson and M. Suzuki equally contributed to this work.

Key Words. epidermal growth factor (EGF), neurogenesis, cortical progenitor, stem cell, cerebral cortex, development







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