Nihon Yakurigaku Zasshi. 2026;161(5):356-362. doi: 10.1254/fpj.26019.
ABSTRACT
To address the low predictability (92% clinical failure rate) and high costs associated with species differences in traditional animal testing, this research advocates for New Approach Methodologies (NAMs) in alignment with the US FDA Modernization Act 2.0. The central achievement presented is the development of a "human Heart-on-a-chip." This microfluidic device co-cultures human iPS-derived cardiomyocytes, fibroblasts, and vascular endothelial cells to mimic living 3D tissue structures and fluid environments. The system demonstrated superior physiological reproducibility compared to conventional methods in evaluating drug responses (e.g., nifedipine) and detecting fatal side effects like QT prolongation. In addition to the heart, applications are advancing across diverse organ and disease models, including the construction of ischemia-reperfusion injury models using kidney chips and pulmonary fibrosis models using lung chips, the evaluation of barrier functions via blood-brain barrier (BBB) chips, and the analysis of interactions between cancer cells and immune cells using cancer chips. It is concluded that these technologies enable high-precision in vitro reproduction of human physiology and pathology, thereby improving the efficiency of drug screening, reducing economic losses, and accelerating the paradigm shift toward the 3Rs (Replacement, Reduction, and Refinement) in animal experimentation.
PMID:42686555 | DOI:10.1254/fpj.26019