Culturing on decellularized extracellular matrix enhances antioxidant properties of human umbilical cord-derived mesenchymal stem cells.
Culturing on decellularized extracellular matrix enhances antioxidant properties of human umbilical cord-derived mesenchymal stem cells.
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在脱细胞细胞外基质上培养可增强人脐带源间充质干细胞的抗氧化特性。
DOI：
10.1016/j.msec.2015.12.090
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发表时间：
2016-04-01
影响因子：
7.9
通讯作者：
He, Fan
中科院分区：
文献类型：
--
作者：
Liu, Xiaozhen;Zhou, Long;Chen, Xi;Liu, Tao;Pan, Guoqing;Cui, Wenguo;Li, Mao;Luo, Zong-Ping;Pei, Ming;Yang, Huilin;Gong, Yihong;He, Fan
关键词：
人脐带间充质干细胞(UC-MSCs)因其具有再生潜能和缺乏伦理问题而在临床应用中引起了极大的兴趣。我们以前的研究表明，去细胞沉积的细胞外基质(ECM)为MSCs提供了一个模拟体内的微环境，促进了细胞的体外扩增。本研究旨在分析UC-MSCs在细胞外基质上培养时的细胞反应，包括活性氧(ROS)、细胞内抗氧化酶和对外源性氧化应激的抵抗力。脱细胞后，细胞沉积的ECM的结构特征为纳米纤维、胶原纤维，基质成分为I型和III型胶原、纤维连接蛋白和层粘连蛋白。与组织培养聚苯乙烯平板相比，细胞外基质培养的UC-MSC增殖率增加了2倍，处于S期的细胞比例增加了2.4倍。ECM培养细胞内ROS和过氧化氢(H_2O_2)水平分别降低41.7%和82.9%。更重要的是，ECM培养的UC-MSCs表现出超氧化物歧化酶和过氧化氢酶等细胞内抗氧化酶的表达和活性增强，沉默的信息调节因子1的表达上调，p38丝裂原激活的蛋白激酶的磷酸化受到抑制。此外，外源性100μM H_2O_2可显著抑制体外培养的UC-MSCs向成骨细胞的分化，而在细胞外基质上培养的UC-MSCs对基质矿化和成骨细胞特异性标志物基因的表达仍具有分化能力。总之，通过提供足够的细胞数量和增强抗氧化能力，脱细胞ECM有望成为UC-MSCs体外扩增的细胞培养平台。
Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) have attracted great interest in clinical application because of their regenerative potential and their lack of ethical issues. Our previous studies showed that decellularized cell-deposited extracellular matrix (ECM) provided an in vivo-mimicking microenvironment for MSCs and facilitated in vitro cell expansion. This study was conducted to analyze the cellular response of UC-MSCs when culturing on the ECM, including reactive oxygen species (ROS), intracellular antioxidative enzymes, and the resistance to exogenous oxidative stress. After decellularization, the architecture of cell-deposited ECM was characterized as nanofibrous, collagen fibrils and the matrix components were identified as type I and III collagens, fibronectin, and laminin. Compared to tissue culture polystyrene (TCPS) plates, culturing on ECM yielded a 2-fold increase of UC-MSC proliferation and improved the percentage of cells in the S phase by 2.4-fold. The levels of intracellular ROS and hydrogen peroxide (H2O2) in ECM-cultured cells were reduced by 41.7% and 82.9%, respectively. More importantly, ECM-cultured UC-MSCs showed enhanced expression and activity of intracellular antioxidative enzymes such as superoxide dismutase and catalase, up-regulated expression of silent information regulator type 1, and suppressed phosphorylation of p38 mitogen-activated protein kinase. Furthermore, a continuous treatment with exogenous 100 μM H2O2 dramatically inhibited osteogenic differentiation of UC-MSCs cultured on TCPS, but culturing on ECM retained the differentiation capacity for matrix mineralization and osteoblast-specific marker gene expression. Collectively, by providing sufficient cell amounts and enhancing antioxidant capacity, decellularized ECM can be a promising cell culture platform for in vitro expansion of UC-MSCs.
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