Abstract
Physiological and morphological properties of the human intestine cannot be accurately mimicked in conventional culture devices such as well plates and petri dishes where intestinal epithelial cells form a monolayer with loose contacts among cells. Here, we report a novel microfluidic cell culture device (μFCCD) that can be used to culture cells as a human intestinal model. This device enables intestinal epithelial cells (Caco-2) to grow three-dimensionally on a porous membrane coated with fibronectin between two polydimethylsiloxane (PDMS) layers. Within 3 days, Caco-2 cells cultured in the μFCCD formed villi- and crypt-like structures with small intercellular spaces, while individual cells were tightly connected to one another through the expression of the tight junction protein occludin, and were covered with a secreted mucin, MUC-2. Caco-2 cells cultured in the μFCCD for 3 days were less susceptible to bacterial attack than those cultured in transwell plates for 21 days. μFCCD-cultured Caco-2 cells also displayed physiologically relevant absorption and paracellular transport properties. These results suggest that our intestinal model more accurately mimics the morphological and physiological properties of the intestine in vivo than the conventional transwell culture model.
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Acknowledgments
This work was supported by a grant from the Korea Science and Engineering Foundation (KOSEF) funded by the Korea government (MOST) (#2012-0001138), and by a grant from the Public Welfare & Safety Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (#2012R1A2A2A01012221 and #2012-0006522). JHS and BL acknowledges support from Hongik University Research Fund.
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Chi, M., Yi, B., Oh, S. et al. A microfluidic cell culture device (μFCCD) to culture epithelial cells with physiological and morphological properties that mimic those of the human intestine. Biomed Microdevices 17, 58 (2015). https://doi.org/10.1007/s10544-015-9966-5
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DOI: https://doi.org/10.1007/s10544-015-9966-5