Institute of Physics, University Münster, Germany.
Biomaterials. 2013 Nov;34(33):8131-9. doi: 10.1016/j.biomaterials.2013.07.025. Epub 2013 Jul 23.
Pluripotent stem cells have the potential to develop into all cell types of the adult body. Besides chemical and mechanical cues, topographical effect of surfaces could also contribute to the development of new therapies in regenerative medicine. In the present study, we tested the effects of nanograting substrates with different widths (width:350 nm/2 μm/5 μm, height: 300 nm) on human induced pluripotent stem cells (hiPSCs), in particular regarding the commitment of stem cell differentiation to desired phenotypes. We found that nuclei of hiPSCs could align and elongate in the direction of the nano/microstructure, whereas they distributed randomly on flat surfaces. The contact guidance significantly increased when the cells were cultured on the surface with smaller pitch. Gene expression profiling by real-time PCR and immunostaining showed significant up-regulation of neuronal markers on nanostructured substrates either with solely topographical cues or combined with pre-neuronal induction. A width of 350 nm, in particular, induced highest neuronal marker expression. This study demonstrates the significance of topography, especially regarding the width of the structures, in directing differentiation of hiPSCs towards the neuronal lineage. Our study suggests the potential applications of surface topography in clinical regenerative medicine for nerve injury repair.
多能干细胞具有分化为成体所有细胞类型的潜能。除了化学和机械线索外，表面的形貌效应也可能有助于再生医学中新型治疗方法的发展。在本研究中，我们测试了不同宽度（宽度：350nm/2μm/5μm，高度：300nm）纳米光栅基底对人诱导多能干细胞（hiPSCs）的影响，特别是关于干细胞分化为所需表型的定向作用。我们发现 hiPSCs 的细胞核可以在纳米/微结构的方向上排列和伸长，而在平面表面上则随机分布。当细胞在具有较小节距的表面上培养时，接触导向显著增加。实时 PCR 和免疫染色的基因表达谱分析表明，在纳米结构基底上，无论是仅具有形貌线索还是与前神经元诱导相结合，神经元标记物的表达均显著上调。特别是 350nm 的宽度诱导出最高的神经元标记物表达。这项研究表明了形貌，特别是结构宽度在定向 hiPSCs 向神经元谱系分化中的重要性。我们的研究提示了表面形貌在神经损伤修复的临床再生医学中的潜在应用。
