Heart disease remains the leading cause of death worldwide, yet progress in understanding and treating cardiac disorders is limited by the shortcomings of existing experimental models. Traditional animal models often fail to capture human-specific cardiac biology, while conventional two-dimensional cell cultures lack the functional and structural complexity of heart tissue. These challenges have fueled growing interest in regenerative medicine approaches that more accurately model human heart development, disease mechanisms, and therapeutic responses, with stem cell–derived cardiac organoids emerging as a promising platform.
These three-dimensional, self-organizing tissues recapitulate key aspects of early cardiac development and enable studies of congenital heart defects, drug-induced cardiotoxicity, and personalized therapies. Despite their promise, most cardiac organoids remain developmentally immature and poorly vascularized, limiting their translational relevance. This limitation arises from the fact that the mechanical forces essential for cardiac development in vivo are not sufficiently reproduced in organoid systems.
To address this gap, a team of researchers led by Professor
Yongdoo Park from the Department of Biomedical Sciences, Korea University, Republic of Korea, investigated whether applying magnetic torque stimulation (MTS) to three-dimensional cardiac organoids can help mimic the mechanical forces experienced during early heart development. The study was made available online on 23 October 2025, and published in Volume 208 of the journal Acta Biomaterialia on December 2025.
The researchers employed an experimental in vitro approach to examine how mechanical stimulation affects cardiac organoid development. Human embryonic stem cells were differentiated into three-dimensional cardiac organoids, which were incorporated with surface-bound magnetic particles. A custom magnetic torque was applied during a defined early developmental window to mimic physiological cardiac mechanics. Organoid maturation and vascularization were evaluated using molecular, structural, and functional analyses, including gene and protein expression profiling, immunofluorescence imaging, beating and calcium transient measurements, and transcriptomic analysis, enabling systematic assessment of mechanotransduction-driven cardiac development.
The findings revealed that mechanical torque significantly enhanced cardiac organoid maturation. "Torque-stimulated activated mechanotransduction pathways, with accompanying improvements in cardiac differentiation, maturation, and vascularization," says Prof. Park.
Mechanically matured cardiac organoids represent a promising platform for improving drug safety testing by providing more accurate, human-relevant models for cardiotoxicity screening and reducing reliance on animal studies. As these organoids incorporate vascular features, they may serve as dependable and reproducible laboratory models across different studies. Over the longer term, torque-stimulated cardiac organoids could support patient-specific disease modeling and personalized treatment strategies, while also offering a powerful system for elucidating how mechanical, molecular, and cellular cues interact to shape early human cardiac development. As cardiac organoids mature and incorporate vascular complexity, they offer increasingly reliable human-based models that can be consistently applied across laboratories.
"Our study opens new avenues for studying cardiac development, disease mechanisms, and therapeutic responses in systems that more closely reflect human physiology. In addition, the platform provides a reliable and reproducible model that can also be extended to other organoid systems in which mechanical cues play a key regulatory role. By reducing dependence on animal models, such platforms can accelerate drug discovery and testing, contributing to safer and more personalized treatment decisions," concludes Prof. Park.
