In vitro propagation and inducible differentiation of multipotential progenitor cells from human fetal brain

Central nervous system neurons and glia arise from undifferentiated embryonic neuroepithelial cells. Such progenitor cells from the human fetal forebrain can be propagated in vitro for extended periods, when grown on non-adhesive substrates in medium containing epidermal growth factor and insulin-like growth factor-1. These actively-dividing cells can be induced to differentiate into a variety of histochemically-characterized neurons and glia consistent with their forebrain origin. Electrophysiological recording indicates that differentiated neurons derived from these progenitors mature slowly, and display a range of glutamate- and GABA-mediated conductances characteristic of normal mammalian forebrain neurons. Our observations support a role for these trophic factors in normal development of the human brain. The methods described here may provide abundant normal, untransformed human forebrain neurons and glia for research and therapeutic applications.