Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage
Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage
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DOI：
10.1016/j.yexcr.2007.02.031
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发表时间：
2007-05-15
影响因子：
3.7
通讯作者：
Leong, Kam W.
中科院分区：
文献类型：
--
作者：
Yim, Evelyn K. F.;Pang, Stella W.;Leong, Kam W.
人间充质干细胞 (hMSC) 通过在神经元诱导培养基中培养已被证明可以转分化为神经元样细胞，但其机制尚不清楚。地形还可以影响细胞反应，包括增强祖细胞的分化。由于体内细胞外基质 (ECM) 包含纳米尺度的形貌，我们假设纳米形貌可以影响干细胞分化为特定的非默认途径，例如 hMSC 的转分化。在宽度为 350 nm 的纳米光栅上研究了 hMSC 的分化和增殖。 hMSC 的细胞骨架和细胞核沿着纳米光栅排列和拉长。基因分析和免疫染色显示，与无图案和微图案对照相比，神经元标记物（例如微管相关蛋白 2 (MAP2)）显着上调。纳米形貌与视黄酸等生化信号的结合进一步增强了神经元标记物表达的上调，但纳米形貌在无图案表面上表现出比单独视黄酸更强的效果。这项研究证明了纳米形貌在指导成体干细胞分化中的重要性。 (c) 2007 Elsevier Inc. 保留所有权利。
Human mesenchymal stem cells (hMSCs) have been shown to trans-differentiate into neuronal-like cells by culture in neuronal induction media, although the mechanism is not well understood. Topography can also influence cellular responses including enhanced differentiation of progenitor cells. As extracellular matrix (ECM) in vivo comprises topography in the nanoscale, we hypothesize that nanotopography could influence stem cell differentiation into specific non-default pathways, such as transdifferentiation of hMSCs. Differentiation and proliferation of hMSCs were studied on nanogratings of 350 nm width. Cytoskeleton and nuclei of hMSCs were aligned and elongated along the nanogratings. Gene profiling and immunostaining showed significant up-regulation of neuronal markers such as microtubule-associated protein 2 (MAP2) compared to unpatterned and micropatterned controls. The combination of nanotopography and biochemical cues such as retinoic acid further enhanced the up-regulation of neuronal marker expressions, but nanotopography showed a stronger effect compared to retinoic acid alone on unpatterned surface. This study demonstrated the significance of nanotopography in directing differentiation of adult stem cells. (c) 2007 Elsevier Inc. All rights reserved.