Harris Greg M, Piroli Maria E, Jabbarzadeh Ehsan
Department of Chemical Engineering, University of South Carolina, SC 29208.
Department of Biomedical Engineering, University of South Carolina, SC 29208.
Adv Funct Mater. 2014 Apr 23;24(16):2396-2403. doi: 10.1002/adfm.201303400.
A wide variety of environmental factors including physical and biochemical signals are responsible for stem cell behavior and function. In particular, matrix elasticity and cell shape have been shown to determine stem cell function, yet little is known about the interplay between how these physical cues control cell differentiation. For the first time, by using ultraviolet (UV) lithography to pattern poly(ethylene) glycol (PEG) hydrogels we are able to manufacture microenvironments capable of parsing the effects of matrix elasticity, cell shape, and cell size in order to explore the relationship between matrix elasticity and cell shape in mesenchymal stem cell (MSC) lineage commitment. Our data shows that cells cultured on 1,000 μm circles, squares, and rectangles were primarily adipogenic lineage regardless of matrix elasticity, while cells cultured on 2,500 and 5,000 μm shapes more heavily depended on shape and elasticity for lineage specification. We further went on to characterize how modifying the cell cytoskeleton through pharmacological inhibitors can modify cell behavior. By showing MSC lineage commitment relationships due to physical signals, this study highlights the importance of cell shape and matrix elasticity in further understanding stem cell behavior for future tissue engineering strategies.
包括物理和生化信号在内的多种环境因素决定了干细胞的行为和功能。特别是，基质弹性和细胞形状已被证明可决定干细胞功能，但对于这些物理信号如何控制细胞分化之间的相互作用却知之甚少。首次通过使用紫外光刻技术对聚乙二醇（PEG）水凝胶进行图案化处理，我们能够制造出能够解析基质弹性、细胞形状和细胞大小影响的微环境，以探索间充质干细胞（MSC）谱系定向中基质弹性与细胞形状之间的关系。我们的数据表明，在1000μm的圆形、方形和矩形上培养的细胞，无论基质弹性如何，主要为脂肪生成谱系，而在2500μm和5000μm形状上培养的细胞在谱系指定方面对形状和弹性的依赖性更强。我们进一步研究了通过药理学抑制剂改变细胞骨架如何能够改变细胞行为。通过展示物理信号导致的MSC谱系定向关系，本研究突出了细胞形状和基质弹性在进一步理解未来组织工程策略中干细胞行为方面的重要性。
