Induction and regulation of differentiation in neural stem cells on ultra-nanocrystalline diamond films
Induction and regulation of differentiation in neural stem cells on ultra-nanocrystalline diamond films
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DOI：
10.1016/j.biomaterials.2010.03.061
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发表时间：
2010-07-01
期刊：
影响因子：
14
通讯作者：
Chiu, Ing-Ming
中科院分区：
文献类型：
--
作者：
Chen, Ying-Chieh;Lee, Don-Ching;Chiu, Ing-Ming
研究了超纳米晶金刚石 (UNCD) 与神经干细胞 (NSC) 的相互作用，以评估其作为生物材料的潜力。将氢封端的 UNCD (H-UNCD) 薄膜与标准级聚苯乙烯就其对 NSC 分化的影响进行比较。当 NSC 在补充有低浓度血清且不含任何分化因子的培养基中在这些基质上培养时，H-UNCD 膜自发诱导 NSC 上的神经元分化。通过使用已知可抑制 Erk1/2 激活的 U0126 直接抑制 NSC 中丝裂原激活蛋白激酶/细胞外信号调节激酶1/2 (MAPK/Erk1/2) 信号通路，我们证明 Erk1/2 通路的增强是 H-UNCD 诱导 NSC 分化的作用之一。此外，针对整合素β1亚基的功能阻断抗体抑制了H-UNCD膜上的神经元分化。该结果证明整合素β1参与H-UNCD介导的神经元分化。机制研究揭示了细胞对 H-UNCD 膜的粘附与粘着斑激酶 (Fak) 相关，并启动了 MAPK/Erk1/2 信号传导。我们的研究表明，在缺乏分化因子的情况下，H-UNCD 膜介导的 NSC 分化涉及纤连蛋白-整合素 beta 1 和 Fak-MAPK/Erk 信号通路。这些观察结果提高了使用UNCD作为中枢神经系统移植和组织工程生物材料的潜力。 (c) 2010 Elsevier Ltd. 保留所有权利。
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 beta 1 subunit inhibited neuronal differentiation on H-UNCD films. This result demonstrated the involvement of integrin beta 1 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 beta 1 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. (c) 2010 Elsevier Ltd. All rights reserved.