Hepatocyte growth factor promotes proliferation and neuronal differentiation of neural stem cells from mouse embryos

Jouji Kokuzawa, Shinichi Yoshimura, Hideomi Kitajima, Jun Shinoda, Yasuhiko Kaku, Toru Iwama, Ryuichi Morishita, Takuya Shimazaki, Hideyuki Okano, Takahiro Kunisada, Noboru Sakai

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40 Citations (Scopus)


Hepatocyte growth factor (HGF), originally cloned as a hepatocyte mitogen, has recently been reported to exhibit neurotrophic activity in addition to being expressed in different parts of the nervous system. At present, the effects of HGF on neural stem cells (NSCs) are not known. In this study, we first report the promoting effect of HGF on the proliferation of neurospheres and neuronal differentiation of NSCs. Medium containing only HGF was capable of inducing neurosphere formation. Addition of HGF to medium containing fibroblast growth factor 2 or epidermal growth factor increased both the size and number of newly formed neurospheres. More neurons were also obtained when HGF was added in differentiation medium. In contrast, neurosphere numbers were reduced after repeated subculture by mechanical dissociation, suggesting that HGF-formed neurospheres comprised predominantly progenitor cells committed to neuronal or glial lines. Together, these results suggest that HGF promotes proliferation of neurospheres and neuronal differentiation of NSCs derived from mouse embyos.

Original languageEnglish
Pages (from-to)190-197
Number of pages8
JournalMolecular and Cellular Neuroscience
Issue number1
Publication statusPublished - 2003 Sep 1


ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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