A majority of such systems expose the cells to laminar flow within microchannels this fluid flow may be adjusted to control local tissue-to-fluid ratio in the channels. A few multi-compartment microfluidic systems, which provide the simultaneous co-culture of different tissues, were described previously. First of all, these systems should be superior to the organotypical single organ equivalents, secondly, they should reflect systems biology of a human organism at a smaller scale by retaining functional connectivity of cultured organ and tissue representatives. These are some necessary requirements for “human-on-a-chip” systems. These platforms open the avenue toward true systems biology driven modeling of the both normal human physiology and various pathological processes. Recently, multi-organ platforms, also known as “human-on-a-chip”, started to emerge as viable alternative for the laboratories involved in modeling of human diseases and drug development including target-based screening, and phenotypic screening. Microfluidic devices are designed to culture the cells under continuous perfusion and physiological shear stress in order to recapitulate the functions of the cells in culture, taking into account the specific tissue- and organ-level circulatory conditions. As an in vitro approach with a great predictive power for human drug response it has a potential in the reduction of costly failures in the evaluation of drug efficacy and safety.
The main goal of microfluidic organotypic chips is the emulation of human physiology on a miniature scale. 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.Ĭurrent methodology for evaluating novel drug candidates in preclinical models is far from being perfect due to the difference in the metabolism of laboratory animals and humans, the limitations of single component in vitro systems and the human body, and the restrictions of in silico modeling. Moreover, the sets of miRNAs secreted at the apical surface of Caco-2 monolayers grown in conventional 2D culture and in microfluidic device differ. 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. When basic electrical parameters of Caco-2 monolayers were evaluated using impedance spectrometry and MTT assays, no differences were noted.
ARTIFICIAL ACADEMY 2 3P SERIES
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. Recent need for incorporating barrier tissue into multi-organ chips calls for inclusion of Caco-2 cells into microperfused environment.
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.
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