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首页> 外文期刊>Journal of biomedical materials research. Part B, Applied biomaterials. >Topographical extracellular matrix cues on anticancer drug-induced cytotoxicity in stem cells
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Topographical extracellular matrix cues on anticancer drug-induced cytotoxicity in stem cells

机译：抗癌药物诱导的干细胞诱导细胞毒性的地形细胞外基质提示

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In recent years, cell chip-based platforms have begun to show promise as a means of corroborating the findings of in vivo animal tests for cytotoxicity, and perhaps in the future partially replacing the need for such animal models. In contrast to the conventional culture methods, micro- and nanofabrication techniques can be utilized to provide a set of mechanostimulatory signals to the cells that mimic the context of extracellular matrix (ECM) of the tissue in which a particular cell line resides. Here, we report periodic lateral topographic striations, with a pitch ranging approximately from 200 to 800 nm with an intention to mimic a common geometry of fibrils in the ECM such as collagen or elastin, as a platform for investigating anticancer drug-induced cytotoxicity in stem cells. The ECM cues could facilitate perimeter, elongation, and gap junction formation of mesenchymal stem cells (MSCs), which eventually influenced the fate of cells in terms of death and survival against the common chemotherapeutic agent cisplatin. Interestingly, the appropriate inhibition of gap junctions of MSCs on the ECM mimicking substrates could prevent the cisplatin-induced cytotoxicity through the inhibition of the cisplatin-induced death signal communication' as compared to that on the flat substrates. Our results imply that nanoscale topography is an important consideration for chip-based cytotoxicity assays, which uniquely enable the consideration and rational design of ECM-like topographic features, and furthermore, that the natural topography of the ECM in the context of stem cell niches may serve as an important indicator for chemotherapeutic agent sensitivity. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1320-1327, 2015.
机译：近年来，基于细胞芯片的平台已经开始表现出承诺，作为证实体内动物试验的细胞毒性研究的方法，也许在未来部分地取代了对这种动物模型的需求。与常规培养方法相比，可以利用微型和纳米制纳米制衡技术向细胞提供一组统一信号，其模仿特定细胞系所在的组织的细胞外基质（ECM）的上下文。在这里，我们报告了周期性的横向地形纹条件，间距约为200至800nm，其目的是模拟ECM中的纤维蛋白的常见几何形状，例如胶原蛋白或弹性蛋白，作为研究抗癌药物诱导的细胞毒性的平台细胞。 ECM提示可以促进间充质干细胞（MSCs）的周长，伸长和间隙结形成，其最终影响了细胞的命运，以对常见的化学治疗剂顺铂的死亡和存活。有趣的是，通过抑制顺铂诱导的死亡信号通信，对ECM模拟底物对ECM模拟底物的适当抑制MSCs的间隙结料可以通过抑制顺铂诱导的死亡信号通信'。我们的结果意味着纳米级地形是基于芯片的细胞毒性测定的重要考虑因素，其唯一能够使ECM样地形特征的考虑和合理设计能够进行，而且，ECM在干细胞龛的背景下的自然地形作为化学治疗剂敏感性的重要指标。 （c）2014年Wiley期刊，Inc.J生物保解员AP：苹果生物摩特，103B：1320-1327,2015。

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