Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 3400 N Charles St, Baltimore, MD 21218, USA.
Biomaterials. 2010 Dec;31(34):9031-9. doi: 10.1016/j.biomaterials.2010.08.021. Epub 2010 Aug 24.
Stem cells display sensitivity to substrate presentation of topographical cues via changes in cell morphology. These biomechanical responses may be transmitted to the nucleus through cytoskeletal-linked signaling pathways. Here we investigate the influence of aligned substratum topography on the cell morphology and subsequently, the neuronal differentiation capabilities of adult neural stem cells (ANSCs). ANSCs that were cultured on aligned fibers elongated along the major fiber axis. Upon induction of differentiation with retinoic acid, a higher fraction of cells on aligned fibers exhibited markers of neuronal differentiation as compared with cells on random fiber or unpatterned surfaces. This effect was in part due to substrate selectivity, whereby aligned fiber substrates were less receptive to the attachment and continued survival of oligodendrocytes than random fiber or unpatterned substrates. Substrate-induced elongation alone was also effective in upregulating canonical Wnt signaling in ANSCs, which was further potentiated by retinoic acid treatment. These findings suggest a mechanism by which morphological control of stem cells operates in concert with biochemical cues for cell fate determination.
干细胞通过细胞形态的变化对基质呈现的拓扑结构线索表现出敏感性。这些生物力学反应可以通过细胞骨架连接的信号通路传递到细胞核。在这里，我们研究了取向基底形貌对细胞形态的影响，进而研究了成年神经干细胞（ANSCs）的神经元分化能力。在定向纤维上培养的 ANSCs 沿主要纤维轴伸长。在用维甲酸诱导分化后，与随机纤维或无图案表面上的细胞相比，在定向纤维上的更高比例的细胞表现出神经元分化的标志物。这种效应部分归因于基底选择性，即与随机纤维或无图案基底相比，定向纤维基底对少突胶质细胞的附着和持续存活的接受性较低。单独的基质诱导伸长也能有效地上调 ANSCs 中的经典 Wnt 信号通路，维甲酸处理进一步增强了这种作用。这些发现表明了一种机制，即干细胞的形态控制与细胞命运决定的生化线索协同作用。
