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一种由可拉伸微流控装置诱导泡沫细胞形成的体外模型。

An in vitro model of foam cell formation induced by a stretchable microfluidic device.

机构信息

College of Life Sciences, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, China.

出版信息

Sci Rep. 2019 May 16;9(1):7461. doi: 10.1038/s41598-019-43902-3.

Abstract

Although a variety of animal models of atherosclerosis have been developed, these models are time-consuming and costly. Here, we describe an in vitro model to induce foam cell formation in the early stage of atherosclerosis. This model is based on a three-dimension co-culture system in a stretchable microfluidic device. An elastic membrane embedded in the microfluidic device is capable of delivering nonuniform strain to vascular smooth muscle cells, endothelial cells and monocytes adhering thereto, which are intended to mimic the biological environment of blood vessels. Under low-density lipoprotein and stretch treatment, foam cell formation was successfully induced in co-culture with changes in mRNA and protein expression of some related key factors. Subsequently, the model was used to assess the inhibitory effect of atorvastatin on foam cell formation. The results obtained indicate that atorvastatin has a significantly dose-dependent inhibition of foam cell formation, which can be explained by the changes in mRNA and protein expression of the related factors. In principle, the model can be used to study the role of different types of cells in the formation of foam cells, as well as the evaluation of anti-atherosclerotic drugs.

摘要

尽管已经开发出多种动脉粥样硬化动物模型,但这些模型既耗时又昂贵。在这里,我们描述了一种体外模型,可诱导动脉粥样硬化早期的泡沫细胞形成。该模型基于可拉伸微流控装置中的三维共培养系统。微流控装置中嵌入的弹性膜能够对附着其上的血管平滑肌细胞、内皮细胞和单核细胞施加不均匀的应变,旨在模拟血管的生物环境。在低密度脂蛋白和拉伸处理下,共培养中成功诱导了泡沫细胞形成,同时相关关键因子的 mRNA 和蛋白表达发生变化。随后,该模型用于评估阿托伐他汀对泡沫细胞形成的抑制作用。结果表明,阿托伐他汀对泡沫细胞形成具有显著的剂量依赖性抑制作用,这可以通过相关因子的 mRNA 和蛋白表达变化来解释。原则上,该模型可用于研究不同类型细胞在泡沫细胞形成中的作用,以及评估抗动脉粥样硬化药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e92/6522483/25f2a69fe484/41598_2019_43902_Fig1_HTML.jpg

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