Toh Yi-Chin, Zhang Chi, Zhang Jing, Khong Yuet Mei, Chang Shi, Samper Victor D, van Noort Danny, Hutmacher Dietmar W, Yu Hanry
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669, Singapore.
Lab Chip. 2007 Mar;7(3):302-9. doi: 10.1039/b614872g. Epub 2007 Jan 23.
Mammalian cells cultured on 2D surfaces in microfluidic channels are increasingly used in drug development and biological research applications. These systems would have more biological or clinical relevance if the cells exhibit 3D phenotypes similar to the cells in vivo. We have developed a microfluidic channel based system that allows cells to be perfusion-cultured in 3D by supporting them with adequate 3D cell-cell and cell-matrix interactions. The maximal cell-cell interaction was achieved by perfusion-seeding cells through an array of micropillars; and 3D cell-matrix interactions were achieved by a polyelectrolyte complex coacervation process to form a thin layer of matrix conforming to the 3D cell shapes. Carcinoma cell lines (HepG2, MCF7), primary differentiated (hepatocytes) and primary progenitor cells (bone marrow mesenchymal stem cells) were perfusion-cultured for 72 hours to 1 week in the microfluidic channel, which preserved their 3D cyto-architecture and cell-specific functions or differentiation competence. This transparent 3D microfluidic channel-based cell culture system also allows direct optical monitoring of cellular events for a wide range of applications.
在微流控通道的二维表面上培养的哺乳动物细胞越来越多地用于药物开发和生物学研究应用中。如果这些细胞表现出与体内细胞相似的三维表型，那么这些系统将具有更大的生物学或临床相关性。我们开发了一种基于微流控通道的系统，通过支持细胞进行充分的三维细胞间和细胞与基质相互作用，使细胞能够在三维环境中进行灌注培养。通过一系列微柱对细胞进行灌注接种，实现了最大程度的细胞间相互作用；通过聚电解质复合凝聚过程形成一层与三维细胞形状相符的薄基质层，实现了三维细胞与基质的相互作用。将癌细胞系（HepG2、MCF7）、原代分化细胞（肝细胞）和原代祖细胞（骨髓间充质干细胞）在微流控通道中灌注培养72小时至1周，这保留了它们的三维细胞结构以及细胞特异性功能或分化能力。这种基于透明三维微流控通道的细胞培养系统还允许对细胞事件进行直接光学监测，以用于广泛的应用。
