Engineering of adult human neural stem cells differentiation through surface micropatterning
Engineering of adult human neural stem cells differentiation through surface micropatterning
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DOI：
10.1016/j.biomaterials.2011.09.073
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发表时间：
2012-01-01
期刊：
影响因子：
14
通讯作者：
Vaysse, Laurence
中科院分区：
文献类型：
--
作者：
Beduer, Amelie;Vieu, Christophe;Vaysse, Laurence
分化中的神经干细胞和细胞外环境之间的相互作用指导神经系统发育过程中细胞极性的建立。发育中的神经元以接触依赖的方式读取局部基底的物理特性，并检索必要的指导线索。为了通过组织工程修复受损的脑区，生物材料支架必须模拟这种微环境以允许组织再生。为了建立使用微槽表面的有效性，以同时提供给原代成人神经干细胞一个允许的生长环境和指导神经突生长在预先建立的方向，我们已经研究了成人神经干细胞的长期培养从患者活检微槽聚合物。通过利用聚合物模塑技术，我们设计了非细胞毒性的聚二甲基硅氧烷（PDMS）的深微结构表面，表现出各种宽度的微通道。我们的研究结果表明，预涂微图案化的PDMS表面可以作为有效的神经突的指导表面的人神经干细胞。免疫细胞化学分析表明，通道宽度对发育和分化有很大影响。特别地，我们发现了最佳的微通道宽度，其协调了高分化率和神经突沿微通道边缘的明显排列沿着。的微观结构对神经突方向的影响被证明是强烈的细胞密度的影响，证明在对齐效应的起源处的细胞/表面相互作用，是在竞争中与细胞/细胞相互作用倾向于促进相互连接的网络的细胞。考虑到所有这些影响，我们已经能够设计适当的结构，允许获得与平面未图案化表面相当的神经元发育和分化速率，具有有效的神经突引导和长期的细胞活力。(C)2011爱思唯尔有限公司保留所有权利。
Interaction between differentiating neural stem cells and the extracellular environment guides the establishment of cell polarity during nervous system development. Developing neurons read the physical properties of the local substrate in a contact-dependent manner and retrieve essential guidance cues. To restore damage brain area by tissue engineering, the biomaterial scaffold has to mimic this microenvironment to allow organized tissue regeneration. To establish the validity of using microgrooved surfaces in order to simultaneously provide to primary adult human neural stem cells a permissive growth environment and a guide for neurite outgrowth in a pre-established direction, we have studied the long-term culture of adult human neural stem cells from patient biopsies on microgrooved polymers. By exploiting polymer moulding techniques, we engineered non-cytotoxic deep microstructured surfaces of polydimethylsiloxane (PDMS) exhibiting microchannels of various widths. Our results demonstrate that precoated micropatterned PDMS surfaces can serve as effective neurite guidance surfaces for human neural stem cells. Immunocytochemistry analysis show that channel width can impact strongly development and differentiation. In particular we found an optimal microchannel width, that conciliates a high differentiation rate with a pronounced alignment of neurites along the edges of the microchannels. The impact of the microstructures on neurite orientation turned out to be strongly influenced by cell density, attesting that cell/surface interactions at the origin of the alignment effect, are in competition with cell/cell interactions tending to promote interconnected networks of cells. Considering all these effects, we have been able to design appropriate structures allowing to obtain neuron development and differentiation rate comparable to a plane unpatterned surface, with an efficient neurite guidance and a long-term cell viability. (C) 2011 Elsevier Ltd. All rights reserved.