Mesenchymal stem cell fate is regulated by the composition and mechanical properties of collagen-glycosaminoglycan scaffolds
Mesenchymal stem cell fate is regulated by the composition and mechanical properties of collagen-glycosaminoglycan scaffolds
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DOI：
10.1016/j.jmbbm.2011.11.009
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发表时间：
2012-07-01
影响因子：
3.9
通讯作者：
O'Brien, Fergal J.
中科院分区：
文献类型：
--
作者：
Murphy, Clara M.;Matsiko, Amos;O'Brien, Fergal J.
在干细胞生物学中，焦点最近转向细胞外基质（ECM）的内在性质（例如结构、组成和弹性）对干细胞分化的影响。利用胶原-糖胺聚糖（CG）支架作为ECM的类似物，本研究着手确定支架刚度和组成对幼稚间充质干细胞（MSC）分化的分化补充剂的情况下的效果。采用去水热（DHT）和1-乙基-3-3-二甲基氨基丙基碳二亚胺（EDAC）交联处理制备了三种均匀的CG支架，它们具有相同的组成，但具有不同的刚度值：0.5，1和1.5 kPa。此外，通过利用两种糖胺聚糖（GAG）类型：硫酸软骨素（CS）和透明质酸（HyA）研究了支架组合物对MSC分化的影响。结果表明，具有最低刚度（0.5kPa）的支架促进了S 0X 9表达的显著上调，表明MSC在更柔顺的支架中被定向为软骨形成谱系。相反，在最硬的支架（1.5kPa）中发现了最高水平的RUNX 2表达，表明MSC在更硬的支架中定向成骨谱系。此外，结果表明，与CCS支架相比，在CHyA支架内SOX 9的上调水平更高，表明透明质酸进一步影响软骨形成分化。相反，与CHyA支架相比，在CCS支架中观察到增强的RUNX 2表达，表明硫酸软骨素对MSC分化的成骨影响。总之，本研究表明，即使在没有分化补充剂的情况下，支架刚度也可以指导MSC的命运，CG支架内使用的GAG类型进一步增强了这种效果。这些结果对干细胞的治疗用途具有重要意义，并增强了我们对体内微环境对干细胞行为的物理影响的理解。(C)2011爱思唯尔有限公司保留所有权利。
In stem cell biology, focus has recently turned to the influence of the intrinsic properties of the extracellular matrix (ECM), such as structural, composition and elasticity, on stem cell differentiation. Utilising collagen-glycosaminoglycan (CG) scaffolds as an analogue of the ECM, this study set out to determine the effect of scaffold stiffness and composition on naive mesenchymal stem cell (MSC) differentiation in the absence of differentiation supplements. Dehydrothermal (DHT) and 1-ethyl-3-3-dimethyl aminopropyl carbodiimide (EDAC) crosslinking treatments were used to produce three homogeneous CG scaffolds with the same composition but different stiffness values: 0.5, 1 and 1.5 kPa. In addition, the effect of scaffold composition on MSC differentiation was investigated by utilising two glycosaminoglycan (GAG) types: chondroitin sulphate (CS) and hyaluronic acid (HyA). Results demonstrated that scaffolds with the lowest stiffness (0.5 kPa) facilitated a significant up-regulation in SOX9 expression indicating that MSCs are directed towards a chondrogenic lineage in more compliant scaffolds. In contrast, the greatest level of RUNX2 expression was found in the stiffest scaffolds (1.5 kPa) indicating that MSCs are directed towards an osteogenic lineage in stiffer scaffolds. Furthermore, results demonstrated that the level of up-regulation of SOX9 was higher within the CHyA scaffolds in comparison to the CCS scaffolds indicating that hyaluronic acid further influences chondrogenic differentiation. In contrast, enhanced RUNX2 expression was observed in the CCS scaffolds in comparison to the CHyA scaffolds suggesting an osteogenic influence of chondroitin sulphate on MSC differentiation. In summary, this study demonstrates that, even in the absence of differentiation supplements, scaffold stiffness can direct the fate of MSCs, an effect that is further enhanced by the GAG type used within the CG scaffolds. These results have significant implications for the therapeutic uses of stem cells and enhance our understanding of the physical effects of the in vivo microenvironment on stem cell behaviour. (C) 2011 Elsevier Ltd. All rights reserved.