School of Materials Science and Engineering, Nanyang Technological University, Singapore.
Exp Cell Res. 2010 Apr 15;316(7):1159-68. doi: 10.1016/j.yexcr.2010.02.010. Epub 2010 Feb 13.
Stem cell response can be influenced by a multitude of chemical, topological and mechanical physiochemical cues. While extensive studies have been focused on the use of soluble factors to direct stem cell differentiation, there are growing evidences illustrating the potential to modulate stem cell differentiation via precise engineering of cell shape. Fibronectin were printed on poly(lactic-co-glycolic acid) (PLGA) thin film forming spatially defined geometries as a means to control the morphology of bone marrow derived human mesenchymal stem cells (hMSCs). hMSCs that were cultured on unpatterned substrata adhered and flattened extensively (approximately 10,000 microm(2)) while cells grown on 20 microm micropatterend wide adhesive strips were highly elongated with much smaller area coverage of approximately 2000 microm(2). Gene expression analysis revealed up-regulation of several hallmark markers associated to neurogenesis and myogenesis for cells that were highly elongated while osteogenic markers were specifically down-regulated or remained at its nominal level. Even though there is clearly upregulated levels of both neuronal and myogenic lineages but at the functionally relevant level of protein expression, the myogenic lineage is dominant within the time scale studied as determined by the exclusive expression of cardiac myosin heavy chain for the micropatterned cells. Enforced cell shape distortion resulting in large scale rearrangement of cytoskeletal network and altered nucleus shape has been proposed as a physical impetus by which mechanical deformation is translated into biochemical response. These results demonstrated for the first time that cellular shape modulation in the absence of any induction factors may be a viable strategy to coax lineage-specific differentiation of stem cells.
干细胞的反应可以受到多种化学、拓扑和机械物理化学线索的影响。虽然已经有大量研究集中在使用可溶性因子来指导干细胞分化上，但越来越多的证据表明，通过精确设计细胞形状来调节干细胞分化具有潜力。纤维连接蛋白被打印在聚乳酸-共-羟基乙酸（PLGA）薄膜上，形成空间定义的几何形状，作为控制骨髓来源的人类间充质干细胞（hMSC）形态的一种手段。在无图案基底上培养的 hMSC 广泛附着和平整（约 10000μm²），而在 20μm 宽的有图案黏附条上生长的细胞则高度伸长，面积覆盖率较小，约为 2000μm²。基因表达分析显示，高度伸长的细胞上调了与神经发生和肌发生相关的几个标志性标记物，而成骨标记物则被特异性下调或保持在其名义水平。尽管神经元和肌源性谱系的表达水平明显上调，但在研究的功能相关蛋白表达水平上，肌源性谱系是占主导地位的，这是由微图案化细胞中肌球蛋白重链的特异性表达所决定的。细胞骨架网络的大规模重排和细胞核形状的改变导致的强制细胞形状变形，被提出是一种物理动力，通过这种动力，机械变形被转化为生化反应。这些结果首次表明，在没有任何诱导因子的情况下，细胞形状的调节可能是一种可行的策略，可以诱导干细胞的谱系特异性分化。
