Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Lab Chip. 2018 May 1;18(9):1378-1387. doi: 10.1039/c7lc01280b.
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.
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，我们提出了一种新的系统，用于在三维（3D）、类似于体内组织的环境中定量评估癌细胞的侵袭。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孔区域，并使用多层微流控装置制备；癌细胞被包裹在核心中，成纤维细胞被接种在核心周围的壳层区域。由于周围固体壳层区域的物理限制，癌细胞通过微孔进行增殖。通过简单地计算纤维外形成的癌细胞集落，可以对癌细胞的侵袭进行定量分析。该平台可以基于侵袭程度和有无成纤维细胞（NIH-3T3 细胞）存在的情况下癌细胞（A549 细胞）的基因表达，评估抗癌药物的疗效（顺铂、紫杉醇和 5-氟尿嘧啶）。所提出的基于水凝胶纤维的迁移分析可以用于研究 3D 共培养条件下的细胞行为以及药物筛选和评估。
