title: Differentiation into neurons of rat bone marrow-derived mesenchymal stem cells.
abstract: OBJECTIVE
  It has been reported that mesenchymal stem cells (MSCs) can differentiate into neurons as an effect of adding extraneous factors, such as β-mercaptoethanol, dimethyl sulfoxide and butylated hydroxyanisole. However, many of these compounds could harm MSCs and the human body, which restricts their application. We examined whether MSCs could differentiate into neuron-like cells under the influence of natural growth factors, such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1, and neurotrophin 3 (NT-3).
  
  
  METHODS
  MSCs were collected from rat bone marrow using the plastic adherent selection method, and induced in culture media to which was added different combinations of EGF, bFGF, IGF-1 and NT-3. The shape of the induced cells was observed daily and the differentiated cells were characterized by immunocytochemistry with neural-specific markers.
  
  
  RESULTS
  With bFGF and NT-3 in the medium, the induced cells became slim, gradually developing protruding processes, with parts of them forming net- or ring-like structures. Cells with processes showed expression of microtubule-associated protein 2 (MAP2) and nestin (NES), which was enhanced when bFGF and NT-3 were added in combination. However, with IGF-1 added to the medium, there was no evidence of neurite-like processes or any net- or ring-like structures; the MSCs retained their round or slim shape.
  
  
  CONCLUSIONS
  Using natural cytokines in vitro, MSCs successfully differentiated into neuron-like cells. Our study confirms that bFGF and NT-3 exerts a neural-induction effect on the differentiation of MSCs, but that IGF has a rather negative effect on this process.
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Hangzhou First People's Hospital, Hangzhou , Zhejiang 310000, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Guan
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lin
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D064231:Nestin / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D020933:Neurotrophin 3 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; C577486:Nes protein, rat; D064231:Nestin; D020933:Neurotrophin 3; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I
keywords: growth factor; mesenchymal stem cell; neuron differentiation