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

An in vitro model of foam cell formation induced by a stretchable microfluidic device
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可拉伸微流体装置诱导泡沫细胞形成的体外模型

DOI:
10.1038/s41598-019-43902-3
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发表时间:
2019-05-16
期刊:
影响因子:
4.6
通讯作者:
Ding, Yongsheng
Ding, Yongsheng
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gu, Xiaoyang;Xie, Shijie;Ding, Yongsheng

文献摘要

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尽管已经开发了多种动脉粥样硬化动物模型,但这些模型耗时且昂贵。在这里,我们描述了一个体外模型,以诱导泡沫细胞形成早期动脉粥样硬化。该模型基于可拉伸微流体装置中的三维共培养系统。微流控装置内嵌入弹性膜,能够向血管平滑肌细胞、内皮细胞和粘附于其上的单核细胞传递不均匀应变,拟模拟血管的生物环境。在低密度脂蛋白和拉伸作用下,通过改变相关关键因子mRNA和蛋白的表达,成功诱导泡沫细胞形成。随后,利用该模型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明显的剂量依赖性抑制作用,这可能与相关因子mRNA和蛋白表达的变化有关。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,以及抗动脉粥样硬化药物的评价。
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.