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使用微流控梯度发生器在不产生大剪切应力的情况下研究葡萄糖浓度对癌细胞的影响。

Investigation of the Influence of Glucose Concentration on Cancer Cells by Using a Microfluidic Gradient Generator without the Induction of Large Shear Stress.

作者信息

Ishida Tadashi, Shimamoto Takuya, Ozaki Nobuya, Takaki Satoshi, Kuchimaru Takahiro, Kizaka-Kondoh Sinae, Omata Toru

机构信息

Department of Mechano-Micro Engineering, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.

Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Kanagawa 226-8501, Japan.

出版信息

Micromachines (Basel). 2016 Sep 1;7(9):155. doi: 10.3390/mi7090155.

Abstract

A microfluidic device capable of precise chemical control is helpful to mimic tumor microenvironments in vitro, which are closely associated with malignant progression, including metastasis. Cancer cells under a concentration gradient of oxygen and other sustenance materials inside a tumor in vivo have recently been reported to increase the probability of metastasis. The influence of glucose concentration on cancer cells has not been measured well, whereas that of oxygen concentration has been thoroughly examined using microfluidic devices. This is because glucose concentrations can be controlled using microfluidic concentration gradient generators, which trade off temporal stability of the glucose concentration and shear stress on the cells; by contrast, oxygen concentration can be easily controlled without microfluidic device-induced shear stresses. To study cell division and migration responses as a function of glucose concentration, we developed a microfluidic device to observe cell behaviors under various chemical conditions. The device has small-cross-section microchannels for generating a concentration gradient and a large-cross-section chamber for cell culture. With this design, the device can achieve both a cell culture with sufficiently low shear stress on cell activity and a stable glucose concentration gradient. Experiments revealed that a low glucose concentration increased the total migration length of HeLa cells and that HeLa cells under a glucose concentration gradient exhibit random motion rather than chemotaxis.

摘要

一种能够进行精确化学控制的微流控装置有助于在体外模拟肿瘤微环境,肿瘤微环境与包括转移在内的恶性进展密切相关。最近有报道称,体内肿瘤内处于氧气和其他营养物质浓度梯度下的癌细胞转移概率会增加。葡萄糖浓度对癌细胞的影响尚未得到很好的测定,而氧气浓度的影响已使用微流控装置进行了深入研究。这是因为葡萄糖浓度可以使用微流控浓度梯度发生器来控制,该发生器在葡萄糖浓度的时间稳定性和对细胞的剪切应力之间进行权衡;相比之下,氧气浓度可以在没有微流控装置引起的剪切应力的情况下轻松控制。为了研究细胞分裂和迁移对葡萄糖浓度的响应,我们开发了一种微流控装置,以观察各种化学条件下的细胞行为。该装置具有用于产生浓度梯度的小横截面微通道和用于细胞培养的大横截面腔室。通过这种设计,该装置既能在对细胞活性剪切应力足够低的情况下进行细胞培养,又能实现稳定的葡萄糖浓度梯度。实验表明,低葡萄糖浓度增加了HeLa细胞的总迁移长度,并且处于葡萄糖浓度梯度下的HeLa细胞表现出随机运动而非趋化性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e5/6189924/7eba190027b3/micromachines-07-00155-g001.jpg

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