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Micro-physiological system of human lung: The current status and application to drug discovery
1Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.
Abstract:
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.
Insights
Lung-on-a-chip technology offers a human-centric approach to studying lung development and disease. This micro-physiological system (MPS) overcomes limitations of animal models and traditional cell cultures for improved drug discovery.
Area of Science:
- Pulmonary Science
- Biomedical Engineering
- Drug Discovery
Background:
- Traditional animal models and 2D/3D cell cultures fail to accurately replicate human lung physiology, hindering research and drug development.
- Reproducibility issues arise from structural and physiological differences between humans and experimental animals.
- Limitations in current models impede understanding of lung development, function, and disease mechanisms.
Purpose of the Study:
- To review the progress, achievements, and challenges of lung mimetics, particularly "lung-on-a-chip" technology.
- To highlight the application of micro-physiological systems (MPS) in disease modeling and toxicological studies.
- To discuss the potential of lung-on-a-chip systems in accelerating drug discovery for refractory lung diseases.
Main Methods:
- Focus on "lung-on-a-chip" technology and other lung mimetics.
- Review of recent advancements in micro-physiological system (MPS) development.
- Analysis of applications in disease modeling, toxicology, and drug discovery.
Main Results:
- Micro-physiological systems (MPS) like "lung-on-a-chip" enable culturing human cells in an environment mimicking the human body.
- These advanced models show promise in overcoming the limitations of traditional animal and cell culture studies.
- Applications in disease modeling, toxicology, and drug discovery are rapidly expanding globally.
Conclusions:
- "Lung-on-a-chip" technology represents a significant advancement in pulmonary research, offering a more human-relevant experimental platform.
- These systems are crucial for improving the accuracy and efficiency of drug discovery for complex lung conditions.
- Continued development and application of lung mimetics are expected to drive innovation in treating refractory lung diseases.
