Reorganization of Cytoskeleton and Transient Activation of Ca2+ Channels in Mesenchymal Stem Cells Cultured on Silicon Nanowire Arrays
Reorganization of Cytoskeleton and Transient Activation of Ca2+ Channels in Mesenchymal Stem Cells Cultured on Silicon Nanowire Arrays
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DOI：
10.1021/am404276r
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发表时间：
2013-12-25
影响因子：
9.5
通讯作者：
Yang, Mengsu
中科院分区：
文献类型：
--
作者：
Liu, Dandan;Yi, Changqing;Yang, Mengsu
组织工程结合生物细胞和含有化学信号分子的合成材料，形成组织再生的支架。间充质干细胞（MSCs）具有多向分化潜能，是组织工程的重要来源。近年来，人们认识到化学刺激和机械刺激是间充质干细胞粘附和分化的重要介质。虽然对细胞外基质内化学调控因子的理解已经取得了重大进展，但纳米材料对MSC施加的机械刺激的影响及其潜在机制尚不为人所知。目前的研究表明，在垂直排列的硅纳米线（SiNW）阵列上培养的MSC的粘附，增殖和分化显着不同的平面硅片和对照基板。间充质干细胞和硅纳米纤维阵列之间的相互作用导致干细胞优先向骨细胞和软骨细胞分化，而不是在缺乏补充生长因子的情况下向脂肪细胞分化。我们的研究表明，钙离子通道瞬时激活的MSC后，机械刺激，这最终导致激活Ras/Raf/MEK/ERK信号级联调节MSC的粘附，增殖和分化。在干细胞-纳米线相互作用期间，牵张介导的瞬时Ca 2+离子通道激活和细胞骨架重组可能是MSC在具有特定机械性质的微环境中培养的间充质干细胞的命运中的谱系特异性增强的早期事件。
Tissue engineering combines biological cells and synthetic materials containing chemical signaling molecules to form scaffolds for tissue regeneration. Mesenchymal stem cells (MSCs) provide an attractive source for tissue engineering due to their versatility of multipotent differentiation. Recently, it has been recognized that both chemical and mechanical stimulations are essential mediators of adhesion and differentiation of MSCs. While significant progress has been made on the understanding of chemical regulatory factors within the extracellular matrix, the effects of mechanical stimulation exerted by nanomaterials on MSCs and the underlying mechanisms are less well-known. The present study showed that the adhesion, proliferation, and differentiation of MSCs cultured on vertically aligned silicon nanowire (SiNW) arrays were significantly different from those on flat silicon wafer and control substrates. The interactions between MSCs and the SiNW arrays caused the stem cells to preferentially differentiate toward osteocytes and chondrocytes but not adipocytes in the absence of supplementary growth factors. Our study demonstrated that Ca2+ ion channels were transiently activated in MSCs upon mechanical stimulation, which eventually led to activation of Ras/Raf/MEK/ERK signaling cascades to regulate adhesion, proliferation, and differentiation of MSCs. The stretch-mediated transient Ca2+ ion channel activation and cytoskeleton reorganization during stem cell-nanowire interaction may be early events of lineage-specific potentiation of MSCs in determining the fates of mesenchymal stem cells cultured on microenvironments with specific mechanical properties.