title: Induction and regulation of differentiation in neural stem cells on ultra-nanocrystalline diamond films.
abstract: The interaction of ultra-nanocrystalline diamond (UNCD) with neural stem cells (NSCs) has been studied in order to evaluate its potential as a biomaterial. Hydrogen-terminated UNCD (H-UNCD) films were compared with standard grade polystyrene in terms of their impact on the differentiation of NSCs. When NSCs were cultured on these substrates in medium supplemented with low concentration of serum and without any differentiating factors, H-UNCD films spontaneously induced neuronal differentiation on NSCs. By direct suppression of mitogen-activated protein kinase/extracellular signaling-regulated kinase1/2 (MAPK/Erk1/2) signaling pathway in NSCs using U0126, known to inhibit the activation of Erk1/2, we demonstrated that the enhancement of Erk1/2 pathway is one of the effects of H-UNCD-induced NSCs differentiation. Moreover, functional-blocking antibody directed against integrin beta1 subunit inhibited neuronal differentiation on H-UNCD films. This result demonstrated the involvement of integrin beta1 in H-UNCD-mediated neuronal differentiation. Mechanistic studies revealed the cell adhesion to H-UNCD films associated with focal adhesion kinase (Fak) and initiated MAPK/Erk1/2 signaling. Our study demonstrated that H-UNCD films-mediated NSCs differentiation involves fibronectin-integrin beta1 and Fak-MAPK/Erk signaling pathways in the absence of differentiation factors. These observations raise the potential for the use of UNCD as a biomaterial for central nervous system transplantation and tissue engineering.
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Ying-Chieh
authors.initials: YC
authors.lastname: Chen
authors.forename: Don-Ching
authors.initials: DC
authors.lastname: Lee
authors.forename: Tsung-Yen
authors.initials: TY
authors.lastname: Tsai
authors.forename: Chao-Yang
authors.initials: CY
authors.lastname: Hsiao
authors.forename: Jen-Wea
authors.initials: JW
authors.lastname: Liu
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Kao
authors.forename: Hua-Kuo
authors.initials: HK
authors.lastname: Lin
authors.forename: Huang-Chin
authors.initials: HC
authors.lastname: Chen
authors.forename: Thomas Joseph
authors.initials: TJ
authors.lastname: Palathinkal
authors.forename: Way-Faung
authors.initials: WF
authors.lastname: Pong
authors.forename: Nyan-Hwa
authors.initials: NH
authors.lastname: Tai
authors.forename: I-Nan
authors.initials: IN
authors.lastname: Lin
authors.forename: Ing-Ming
authors.initials: IM
authors.lastname: Chiu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002070:Butadienes / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D018130:Diamond / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009570:Nitriles / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013499:Surface Properties
chemical_list: D015415:Biomarkers; D002070:Butadienes; D020099:Coated Materials, Biocompatible; D004791:Enzyme Inhibitors; D005353:Fibronectins; D019012:Integrin beta1; D009570:Nitriles; C113580:U 0126; D018130:Diamond; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases