Effects of substrate stiffness on adipogenic and osteogenic differentiation of human mesenchymal stem cells.
Effects of substrate stiffness on adipogenic and osteogenic differentiation of human mesenchymal stem cells.
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DOI：
10.1016/j.msec.2014.03.048
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发表时间：
2014-07
期刊：
影响因子：
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通讯作者：
Wen Zhao;Xiaowei Li;Xiaoyan Liu;Ning Zhang;X. Wen
中科院分区：
文献类型：
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作者：
Wen Zhao;Xiaowei Li;Xiaoyan Liu;Ning Zhang;X. Wen
除了生化信号外，基质的机械特性也被证明可以调节细胞表型。在这项研究中，我们检测了基质硬度对成人骨髓间充质干细胞（hMSCs）分化成脂肪细胞和成骨细胞的影响。以巯基功能化透明质酸（HA-SH）和巯基功能化重组人明胶（Gtn-SH）为基础，通过聚乙二醇四丙烯酸酯（PEGTA）交联制备了一种化学修饰的细胞外基质衍生的高生物相容性水凝胶作为模型体系。通过调节交联密度来控制水凝胶的刚度。在成脂和成骨条件下，用不同硬度的水凝胶培养人骨髓间充质干细胞。采用油红O染色和f -肌动蛋白染色分别评价成脂和成骨分化过程中细胞形态的变化。用逆转录聚合酶链反应（RT-PCR）测定细胞基因表达与水凝胶硬度的关系。结果支持了一种假设，即骨髓间充质干细胞的成脂和成骨分化倾向于发生在与其在体内微环境中相似的硬度基质上。
Substrate mechanical properties, in addition to biochemical signals, have been shown to modulate cell phenotype. In this study, we inspected the effects of substrate stiffness on human mesenchymal stem cells (hMSCs) derived from adult human bone marrow differentiation into adipogenic and osteogenic cells. A chemically modified extracellular matrix derived and highly biocompatible hydrogel, based on thiol functionalized hyaluronic acid (HA-SH) and thiol functionalized recombinant human gelatin (Gtn-SH), which can be crosslinked by poly (ethylene glycol) tetra-acrylate (PEGTA), was used as a model system. The stiffness of the hydrogel was controlled by adjusting the crosslinking density. Human bone marrow MSCs were cultured on the hydrogels with different stiffness under adipogenic and osteogenic conditions. Oil Red O staining and F-actin staining were applied to assess the change of cell morphologies under adipogenic and osteogenic differentiation, respectively. Gene expression of cells was determined with reverse transcription polymerase chain reaction (RT-PCR) as a function of hydrogel stiffness. Results support the hypothesis that adipogenic and osteogenic differentiation of hMSCs are inclined to occur on substrate with stiffness similar to theirin vivomicroenvironments.