A High Concentration of Epidermal Growth Factor Increases the Growth and Survival of Neurogenic Radial Glial Cells Within Human Neurosphere Cultures

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 epidermal growth factor (EGF) to drive the proliferation of these cells. Here, we show that 100 ng/ml 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 100 ng/ml EGF was significantly higher than from 20 ng/ml EGF. Thus, high concentrations of EGF increase the survival of a highly neurogenic human radial glial cell.