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Effect of growth factors on proliferation and phenotypic differentiation of human fetal neural stem cells
Author(s) -
Tarasenko Yevgeniya I.,
Yu Yongjia,
Jordan Paivi M.,
Bottenstein Jane,
Wu Ping
Publication year - 2004
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20316
Subject(s) - basic fibroblast growth factor , biology , leukemia inhibitory factor , epidermal growth factor , neural stem cell , neurosphere , microbiology and biotechnology , growth factor , cellular differentiation , neurite , immunology , stem cell , in vitro , cell culture , biochemistry , adult stem cell , cytokine , interleukin 6 , receptor , genetics , gene
Human fetal neural stem cells (hNSCs) can be expanded in vitro by mitogens or growth factors, such as basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and/or leukemia inhibitory factor (LIF). Their effects on proliferation rate and differentiation pattern of hNSCs, however, have not been fully characterized. In this study, we cultured hNSCs in seven regimens, including bFGF, EGF, and LIF, either alone or in combinations. Cells were maintained as neurospheres in treatment media for various periods, up to six passages. A combination of bFGF, EGF, and LIF expanded hNSCs more efficiently than any other treatment as determined by counting total cell numbers using a trypan blue exclusion assay, a WST‐1 cell viability assay, and a bromodeoxyuridine incorporation flow cytometric analysis. Differentiation patterns of hNSCs expanded under different conditions were also analyzed. We reported previously that hNSCs primed in vitro with a combination of bFGF, heparin, and laminin (FHL) induced neuronal differentiation toward a cholinergic phenotype. In this study, we show that the FHL priming increases neuronal differentiation while decreasing astroglial generation in all treatment groups as determined by immunostaining. However, cells proliferated under different growth factor conditions do vary in their phenotypic differentiation patterns. Particularly, significant generation of cholinergic cells was observed only in hNSCs expanded with EGF/bFGF or EGF/bFGF/LIF, but not with other treatment regimens, even when they are exposed to the same priming procedure. Our results indicate that hNSCs are highly plastic, with their proliferation and differentiation potential dependent on different growth factor treatments. © 2004 Wiley‐Liss, Inc.