Organ‐on‐a‐Chip Technology for Reproducing Multiorgan Physiology

Abstract

In the drug development process, the accurate prediction of drug efficacy and toxicity is important in order to reduce the cost, labor, and effort involved. For this purpose, conventional 2D cell culture models are used in the early phase of drug development. However, the differences between the in vitro and the in vivo systems have caused the failure of drugs in the later phase of the drug-development process. Therefore, there is a need for a novel in vitro model system that can provide accurate information for evaluating the drug efficacy and toxicity through a closer recapitulation of the in vivo system. Recently, the idea of using microtechnology for mimicking the microscale tissue environment has become widespread, leading to the development of "organ-on-a-chip." Furthermore, the system is further developed for realizing a multiorgan model for mimicking interactions between multiple organs. These advancements are still ongoing and are aimed at ultimately developing "body-on-a-chip" or "human-on-a-chip" devices for predicting the response of the whole body. This review summarizes recently developed organ-on-a-chip technologies, and their applications for reproducing multiorgan functions.

In Vitro Tissue‐Engineered Skeletal Muscle Models for Studying Muscle Physiology and Disease

“…[272] Improved predictive capacity in future studies will require addition of other tissue-engineered organs, including the gut and intestine to model first-pass metabolism that regulates the concentration and chemical form of any drug that enters the bloodstream. [273] …”

Construction of pancreas–muscle–liver microphysiological system (MPS) for reproducing glucose metabolism

“…Despite these advantages, the attrition rate of drugs continues to be high and the productivity of new drug development process has decreased, resulting in a reluctance to monetarily invest in drug research and development (Peck, Lendrem, Grant, Lendrem, & Isaacs, ). The performance of in vitro models is hindered by the reality that the human body consists of many organs that are functionally interconnected by vascular networks (S. H. Lee & Sung, ). The organs communicate through signal molecules that are transported by blood to other organs via vascular networks.…”

“…Conventional in vitro models for studying glucose metabolism have been limited to static, single‐organ systems. These models are limited in their ability to simulate the relationships between organs, and fail to provide disease models that are physiologically relevant (S. H. Lee & Sung, ). Coculturing and the transfer of media from cell to cell have been proposed as alternative methods, but they are not able to reproduce the time‐dependent dynamics of multiorgan interactions (Choi, Fukuda, Sakoda, & Sakai, ).…”

Cross‐talk of healthy and impaired human tissues for dissection of disease pathogenesis

“…On the contrary, in vitro culture systems offer the advantages of controlled manipulation of experimental conditions for dissecting tissue-to-tissue communication and of accessibility to measurements 2 . The most used in vitro models to study the cross talk between different tissues are based on no-contact co-culture systems, called transwell, where different cell types are cultured on the same dish sharing the same culture medium, but physically separated by a porous membrane.…”

“…Up to now, multiple tissues-on-chip have been developed 4,7 , although the application of these technologies to human primary cells is more limited 5,8,9 . Some studies have been performed to understand the interaction between different tissues in vitro, but mainly cell lines have been used so far, as recently reviewed 2,10 .…”