Micropassage-embedding composite hydrogel fibers enable quantitative evaluation of cancer cell invasion under 3D coculture conditions
Micropassage-embedding composite hydrogel fibers enable quantitative evaluation of cancer cell invasion under 3D coculture conditions
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DOI：
10.1039/c7lc01280b
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发表时间：
2018-05-07
期刊：
影响因子：
6.1
通讯作者：
Seki, Minoru
中科院分区：
文献类型：
--
作者：
Sugimoto, Manami;Kitagawa, Yoichi;Seki, Minoru
细胞迁移和侵袭在生理现象中具有重要意义，包括伤口愈合和癌症转移。在这里，我们提出了一个新的系统，用于定量评估癌细胞在三维（3D），在体内组织样环境中的侵袭。该系统使用复合水凝胶微纤维，其横截面具有相对柔软的微通道区域，并且使用多层微流体装置制备;癌细胞被包封在核心中，成纤维细胞接种在核心周围的壳区域中。由于周围固体壳区域施加的物理限制，癌细胞增殖被引导通过微通道。癌细胞侵袭的定量分析可以简单地通过计数在纤维外形成的癌细胞集落来进行。该平台可根据癌细胞（A549细胞）的侵袭程度和基因表达（有或没有成纤维细胞（NIH-3 T3细胞））来评价抗癌药物（顺铂、紫杉醇和5-氟尿嘧啶）的疗效。所提出的基于水凝胶纤维的迁移测定可用于研究3D共培养条件下的细胞行为以及用于药物筛选和评价。
Cell migration and invasion are of significant importance in physiological phenomena, including wound healing and cancer metastasis. Here we propose a new system for quantitatively evaluating cancer cell invasion in a three-dimensional (3D), in vivo tissue-like environment. This system uses composite hydrogel microfibers whose cross section has a relatively soft micropassage region and that were prepared using a multilayered microfluidic device; cancer cells are encapsulated in the core and fibroblasts are seeded in the shell regions surrounding the core. Cancer cell proliferation is guided through the micropassage because of the physical restriction imposed by the surrounding solid shell regions. Quantitative analysis of cancer cell invasion is possible simply by counting the cancer cell colonies that form outside the fiber. This platform enables the evaluation of anticancer drug efficacy (cisplatin, paclitaxel, and 5-fluorouracil) based on the degree of invasion and the gene expression of cancer cells (A549 cells) with or without the presence of fibroblasts (NIH-3T3 cells). The presented hydrogel fiber-based migration assays could be useful for studying cell behaviors under 3D coculture conditions and for drug screening and evaluation.