Weill Cornell Medical College, Cornell University, New York, NY 10021, USA.
J Biomech. 2010 Nov 16;43(15):3058-62. doi: 10.1016/j.jbiomech.2010.07.015. Epub 2010 Sep 20.
Enhancing cellular mechanosensitivity is recognized as a novel tool for successful musculoskeletal tissue engineering. We examined the hypothesis that mechanosensitivity of human mesenchymal stem cells (hMSCs) is enhanced on nanotopographic substrates relative to flat surfaces. hMSCs were cultured on polymer-demixed, randomly distributed nanoisland surfaces with varying island heights and changes in intracellular calcium concentration, Ca(2+), in response to fluid flow induced shear stress were quantifide. Stem cells cultured on specific scale nanotopographies displayed greater intracellular calcium responses to fluid flow. hMSCs cultured on 10-20nm high nanoislands displayed a greater percentage of cells responding in calcium relative to cells cultured on flat control, and showed greater average Ca(2+) increase relative to cells cultured on other nanoislands (45-80nm high nanoislands). As Ca(2+) is an important regulator of downstream signaling, as well as proliferation and differentiation of hMSCs, this observation suggests that specific scale nanotopographies provide an optimal milieu for promoting stem cell mechanotransduction activity. That mechanical signals and substrate nanotopography may synergistically regulate cell behavior is of significant interest in the development of regenerative medicine protocols.
增强细胞的机械敏感性被认为是成功进行肌肉骨骼组织工程的一种新工具。我们假设，相对于平面，在纳米形貌基底上，人骨髓间充质干细胞（hMSC）的机械敏感性会增强。我们研究了在聚合物解混、随机分布纳米岛表面上培养 hMSC 时，细胞内钙离子浓度 (Ca(2+)) 对流体流动诱导切应力的变化，以检验以下假说：纳米岛高度不同和纳米岛形貌不同时，hMSC 会响应Ca(2+) 的变化。结果显示，在特定尺度纳米形貌上培养的干细胞对流体流动具有更强的细胞内钙反应。与在平面对照培养的细胞相比，在 10-20nm 高纳米岛上培养的细胞中，响应钙的细胞比例更高，与在其他纳米岛上（45-80nm 高纳米岛）培养的细胞相比，Ca(2+) 增加的平均值更高。因为Ca(2+) 是 hMSC 中下游信号转导、增殖和分化的重要调节剂，所以这一观察结果表明，特定尺度的纳米形貌为促进干细胞的机械转导活性提供了最佳环境。机械信号和基底纳米形貌可能协同调节细胞行为，这在再生医学方案的发展中具有重要意义。
