Collagen structure regulates MSCs behavior by MMPs involved cell-matrix interactions
Collagen structure regulates MSCs behavior by MMPs involved cell-matrix interactions
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DOI：
10.1039/c7tb02377d
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发表时间：
2018-01-14
影响因子：
7
通讯作者：
Zhang, Xingdong
中科院分区：
文献类型：
--
作者：
Ni, Yilu;Tang, Zhurong;Zhang, Xingdong
各种支架在细胞龛的形成和间充质干细胞（MSCs）行为的调控方面进行了研究。胶原蛋白是最有前途的组织工程材料之一，但对间充质干细胞与胶原蛋白之间的相互作用仍知之甚少。本研究制备了甲基丙烯酸化胶原（CMA）和明胶（GMA），制备了光交联水凝胶。对衍生物和水凝胶的结构、形态、力学性能和降解行为进行了表征，发现其高级结构是胶原和明胶水凝胶的主要区别。将MSC封装在水凝胶中，并在体外培养14天，有或没有金属蛋白酶组织抑制剂（TIMP）。CCK-8和CLSM显示CMA水凝胶中的细胞比GMA水凝胶中的细胞表现出更好的铺展和增殖。qRT-PCR和蛋白定量分析证实TIMP对金属蛋白酶（MMPs）有抑制作用。由于MMPs的抑制导致MSCs粘附和增殖能力下降，我们认为MMPs的适当降解将产生更多的生物活性域，改善细胞微环境。免疫荧光染色进一步证明了玻连蛋白的分布与MMP-1和MMP-2显著相关。结论是支架材料高级结构的差异被放大为多种生物细胞-基质相互作用的显著差异，并最终导致不同的细胞命运。
Various scaffolds have been studied in the formation of cell niches and regulation of mesenchymal stem cells (MSCs) behaviors. Collagen serves as one of the most promising materials for tissue engineering, but the cell-matrix interactions between MSCs and collagen are still poorly understood. In this study, we prepared methacrylated collagen (CMA) and gelatin (GMA) to form photo cross-linking hydrogels. The structure, morphology, mechanical properties and degradation behaviors of the derivatives and hydrogels were characterized and it was found that the advanced structure was the major difference between collagen and gelatin hydrogels. MSCs were encapsulated in the hydrogels and cultured for 14 days in vitro, with or without the tissue inhibitor of metalloproteinase (TIMP). The CCK-8 and CLSM demonstrated that the cells in the CMA hydrogels showed better spreading and proliferation than those in GMA hydrogels. The qRT-PCR and quantitative protein assay verified the inhibition effect of TIMP on metalloproteinases (MMPs). Since the inhibited MMPs led to inferior MSCs adhesion and proliferation, we considered that the appropriate degradation by MMPs would generate more bioactive domains and improve the cell microenvironment. Immunofluorescence staining further proved that the distribution of vitronectin was significantly related to MMP-1 and MMP-2. It was concluded that the differences in the advanced structures of the scaffold materials were amplified to significant differences in multiple biological cell-matrix interactions, and finally led to different cellular fates.