Differential regulation of morphology and stemness of mouse embryonic stem cells by substrate stiffness and topography
Differential regulation of morphology and stemness of mouse embryonic stem cells by substrate stiffness and topography
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DOI：
10.1016/j.biomaterials.2014.01.066
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发表时间：
2014-04-01
期刊：
影响因子：
14
通讯作者：
Long, Mian
中科院分区：
文献类型：
--
作者：
Lu, Dongyuan;Luo, Chunhua;Long, Mian
干细胞的多能性或坚固性的维持对胚胎的发育和分化至关重要。干细胞的力学或物理微环境，包括细胞外基质的硬度和形态，调节细胞的形态和干性。尽管越来越多的证据表明这些因素在干细胞分化中的重要性，但这些生物物理或生物力学调节因子的影响仍然不够明确。在本研究中，我们应用了一种具有两个弹性和三个形貌的微制聚丙烯酰胺水凝胶基质来系统地测试mESCs的形态、增殖和硬度。分析了这两个因素对特定细胞功能的独立或联合影响。在没有饲养细胞的情况下，细胞能够在聚苯乙烯和聚丙烯酰胺基质上有效生长。基质硬度是通过增强Oct-4和Nanog在柔软的聚丙烯酰胺底物上的表达来保持茎的优势。地形也是通过在凹槽或柱状基板上形成相对平坦的菌落和在六角形基板上形成球状菌落来操纵硬度的关键因素。虽然地形对软基质的影响较小，但在坚硬的、六角形或柱状的基质上，地形对保持细胞的坚固性起到了作用。MESCs还可以及时地在凹槽或六边形衬底上形成3D结构。这些结果进一步加深了对干细胞在模拟生理条件的微环境中的形态和干性的理解。(C)2014爱思唯尔有限公司。保留所有权利。
The maintenance of stem cell pluripotency or sternness is crucial to embryonic development and differentiation. The mechanical or physical microenvironment of stem cells, which includes extracellular matrix stiffness and topography, regulates cell morphology and stemness. Although a growing body of evidence has shown the importance of these factors in stem cell differentiation, the impact of these biophysical or biomechanical regulators remains insufficiently characterized. In the present study, we applied a micro-fabricated polyacrylamide hydrogel substrate with two elasticities and three topographies to systematically test the morphology, proliferation, and sternness of mESCs. The independent or combined impact of the two factors on specific cell functions was analyzed. Cells are able to grow effectively on both polystyrene and polyacrylamide substrates in the absence of feeder cells. Substrate stiffness is predominant in preserving stemness by enhancing Oct-4 and Nanog expression on a soft polyacrylamide substrate. Topography is also a critical factor for manipulating sternness via the formation of a relatively flattened colony on a groove or pillar substrate and a spheroid colony on a hexagonal substrate. Although topography is less effective on soft substrates, it plays a role in retaining cell sternness on stiff, hexagonal or pillar-shaped substrates. mESCs also form, in a timely manner, a 3D structure on groove or hexagonal substrates. These results further the understanding of stem cell morphology and stemness in a microenvironment that mimics physiological conditions. (C) 2014 Elsevier Ltd. All rights reserved.