학술논문
Towards embedding Caco-2 model of gut interface in a microfluidic device to enable multi-organ models for systems biology
Document Type
Report
Author
Source
BMC Systems Biology. March 5, 2019, Vol. 13 Issue Suppl 1
Subject
Language
English
ISSN
1752-0509
Abstract
Author(s): Dmitry Sakharov[sup.1] , Diana Maltseva[sup.1] , Evgeny Knyazev[sup.1] , Sergey Nikulin[sup.1] , Andrey Poloznikov[sup.1] , Sergey Shilin[sup.1] , Ancha Baranova[sup.2,3] , Irina Tsypina[sup.1,4] and Alexander Tonevitsky[sup.1,4,5] Introduction Current methodology [...]
Background A cancer cell line originating from human epithelial colorectal adenocarcinoma (Caco-2 cells) serves as a high capacity model for a preclinical screening of drugs. Recent need for incorporating barrier tissue into multi-organ chips calls for inclusion of Caco-2 cells into microperfused environment. Results This article describes a series of systems biology insights obtained from comparing Caco-2 models cells grown as conventional 2D layer and in a microfluidic chip. When basic electrical parameters of Caco-2 monolayers were evaluated using impedance spectrometry and MTT assays, no differences were noted. On the other hand, the microarray profiling of mRNAs and miRNAs revealed that grows on a microfluidic chip leads to the change in the production of specific miRNA, which regulate a set of genes for cell adhesion molecules (CAMs), and provide for more complete differentiation of Caco-2 monolayer. Moreover, the sets of miRNAs secreted at the apical surface of Caco-2 monolayers grown in conventional 2D culture and in microfluidic device differ. Conclusions When integrated into a multi-tissue platform, Caco-2 cells may aid in generating insights into complex pathophysiological processes, not possible to dissect in conventional cultures. Keywords: Caco-2 cell lines, 2D layer, Microfluidic chip, On-the-chip models
Background A cancer cell line originating from human epithelial colorectal adenocarcinoma (Caco-2 cells) serves as a high capacity model for a preclinical screening of drugs. Recent need for incorporating barrier tissue into multi-organ chips calls for inclusion of Caco-2 cells into microperfused environment. Results This article describes a series of systems biology insights obtained from comparing Caco-2 models cells grown as conventional 2D layer and in a microfluidic chip. When basic electrical parameters of Caco-2 monolayers were evaluated using impedance spectrometry and MTT assays, no differences were noted. On the other hand, the microarray profiling of mRNAs and miRNAs revealed that grows on a microfluidic chip leads to the change in the production of specific miRNA, which regulate a set of genes for cell adhesion molecules (CAMs), and provide for more complete differentiation of Caco-2 monolayer. Moreover, the sets of miRNAs secreted at the apical surface of Caco-2 monolayers grown in conventional 2D culture and in microfluidic device differ. Conclusions When integrated into a multi-tissue platform, Caco-2 cells may aid in generating insights into complex pathophysiological processes, not possible to dissect in conventional cultures. Keywords: Caco-2 cell lines, 2D layer, Microfluidic chip, On-the-chip models