Micro-physiological system of human lung: The current status and application to drug discovery

Various attempts have been made to elucidate the mechanisms of human lung development, its physiological functions, and diseases, in the hope of new drug discovery. Recent technological advancements in experimental animals, cell culture, gene editing, and analytical methods have provided new insights and therapeutic strategies. However, the results obtained from animal experiments are often inconsistent with those obtained from human data because of reproducibility issues caused by structural and physiological differences between mice and humans. In addition, it is not possible to accurately reproduce the internal environment of the human lung structure using conventional two-dimensional (2D) or three-dimensional (3D) cell culture methods. As a result, the micro-physiological system (MPS) technology, such as “lung-on-a-chip” that can culture human cells in a state close to human body environment have been developed, and its applications to disease models, toxicological studies, and drug discovery are accelerated worldwide. Here, we focus on the mimetics of the lung, including “lung-on-a-chip” technology, and review their recent progress, achievements and challenges. Finally, we discuss the role of these chips in drug discovery for refractory lung diseases.