In vitro expansion of a multipotent population of human neural progenitor cells

The isolation and expansion of human neural progenitor cells have important potential clinical applications, because these cells may be used as graft material in cell therapies to regenerate tissue and/or function in patients with central nervous system (CNS) disorders. This paper describes a contin uously dividing multipotent population of progenitor cells in the human emb ryonic forebrain that can be propagated in vitro. These cells can be mainta ined and expanded using a serum-free defined medium containing basic fibrob last growth factor (bFGF), leukemia inhibitory factor (LIF), and epidermal growth factor (EGF). Using these three factors, the cell cultures expand an d remain multipotent for at least 1 year in vitro. This period of expansion results in a 10(7)-fold increase of this heterogeneous population of cells . Upon differentiation, they form neurons, astrocytes, and oligodendrocytes , the three main phenotypes in the CNS. Moreover, GABA-immunoreactive and t yrosine hydroxylase-immunoreactive neurons can be identified. These results demonstrate the feasibility of long-term in vitro expansion of human neura l progenitor cells. The advantages of such a population of neural precursor s for allogeneic transplantation include the ability to provide an expandab le, well-characterized, defined cell source which can form specific neurona l or glial subtypes. (C) 1999 Academic Press.