Although animal experiments are indispensable for preclinical screening in the drug discovery process, various issues such as ethical considerations and species differences remain. To solve these issues, cell-based assays using human-derived cells have been actively pursued. However, it remains difficult to accurately predict drug efficacy, toxicity, and organs interactions, because cultivated cells often do not retain their original organ functions and morphologies in conventional in vitro cell culture systems. In the μTAS research field, which is a part of biochemical engineering, the technologies of organ-on-a-chip, based on microfluidic devices built using microfabrication, have been widely studied recently as a novel in vitro organ model. Since it is possible to physically and chemically mimic the in vitro environment by using microfluidic device technology, maintenance of cellular function and morphology, and replication of organ interactions can be realized using organ-on-a-chip devices. So far, functions of various organs and tissues, such as the lung, liver, kidney, and gut have been reproduced as in vitro models. Furthermore, a body-on-a-chip, integrating multi organ functions on a microfluidic device, has also been proposed for prediction of organ interactions. We herein provide a background of microfluidic systems, organ-on-a-chip, Body-on-a-chip technologies, and their challenges in the future.
Conventional cell-based assays in life science and medical applications can be difficult to maintain functionally over long periods. Microfluidics is an emerging technology with potential to provide integrated environments for cell maintenance, continuous perfusion, and monitoring. In this study, we developed an integrated microfluidic device with on-chip pumping and detection functionalities. The microfluidic structure in the device is divided into two independent channels separated by a semipermeable membrane on which cells are inoculated and cultured. Perfusion and fluorescence measurements of culture media for each channel can be conducted by the on-chip pumping system and optical fiber detection system. Performance of the device was examined through long-term culture and monitoring of polarized transport activity of intestinal tissue models (Caco-2 cells). The cells could be cultured for more than two weeks, and monolayer transport of rhodamine 123 was successfully monitored by on-line fluorescent measurement. This device may have applications in toxicity testing and drug screening.
In this study, we propose a microfluidic cell culture device mimicking the microscopic structure in liver tissue called hepatic cords. The cell culture area of the device was designed to align hepatocytes in two lines in a similar way to hepatic cords. Thanks to the structural design together with a cell seeding procedure, rat primary hepatocytes were successfully aligned in two lines and cultured under perfusion condition. It is shown that aligned hepatocytes gradually self-organize and form bile canaliculi along the hepatic cord-like structure. The present technique to culture hepatocytes with functional bile canaliculi could be used as an alternative to animal testing in the field of drug discovery and toxicological studies, and also be beneficial to tissue engineering applications.
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