Induction and regulation of differentiation in neural stem cells on ultra-nanocrystalline diamond films.
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.
Chen
Ying-Chieh
YC
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan.
Lee
Don-Ching
DC
Tsai
Tsung-Yen
TY
Hsiao
Chao-Yang
CY
Liu
Jen-Wea
JW
Kao
Chien-Yu
CY
Lin
Hua-Kuo
HK
Chen
Huang-Chin
HC
Palathinkal
Thomas Joseph
TJ
Pong
Way-Faung
WF
Tai
Nyan-Hwa
NH
Lin
I-Nan
IN
Chiu
Ing-Ming
IM
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
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