Heart disease remains the leading cause of death globally, with progress in understanding and treating cardiac disorders hindered by limitations in existing experimental models. Traditional animal models often fail to replicate human-specific cardiac biology, and conventional two-dimensional cell cultures lack the functional and structural complexity of heart tissue.
Regenerative medicine approaches, particularly stem cell-derived cardiac organoids, offer a promising platform to address these challenges. These three-dimensional tissues mimic aspects of early cardiac development and are useful for studying congenital heart defects, drug-induced cardiotoxicity, and personalized therapies. However, most cardiac organoids are developmentally immature and poorly vascularized because they do not adequately reproduce the mechanical forces crucial for cardiac development in vivo.
A team of researchers, led by Professor Yongdoo Park from Korea University, Republic of Korea, investigated whether applying magnetic torque stimulation (MTS) to three-dimensional cardiac organoids could mimic the mechanical forces present during early heart development. The study was published in Volume 208 of Acta Biomaterialia in December 2025, with online availability from October 23, 2025.
The researchers used an in vitro approach, differentiating human embryonic stem cells into three-dimensional cardiac organoids that incorporated surface-bound magnetic particles. A custom magnetic torque was applied during an early developmental window to simulate physiological cardiac mechanics. Organoid maturation and vascularization were assessed through molecular, structural, and functional analyses, including gene and protein expression profiling, immunofluorescence imaging, beating and calcium transient measurements, and transcriptomic analysis.
The findings indicated that mechanical torque significantly enhanced cardiac organoid maturation. Professor Park stated that "Torque-stimulated activated mechanotransduction pathways, with accompanying improvements in cardiac differentiation, maturation, and vascularization."
Mechanically matured cardiac organoids offer a platform for enhancing drug safety testing by providing more accurate, human-relevant models for cardiotoxicity screening, potentially reducing the need for animal studies. These organoids, with their vascular features, may serve as dependable and reproducible laboratory models. Long-term applications could include supporting patient-specific disease modeling, personalized treatment strategies, and elucidating the interactions between mechanical, molecular, and cellular cues in early human cardiac development.
Professor Park concluded that the study "opens new avenues for studying cardiac development, disease mechanisms, and therapeutic responses in systems that more closely reflect human physiology." He added that the platform provides a reliable and reproducible model extensible to other organoid systems where mechanical cues are regulatory, potentially accelerating drug discovery and testing, and contributing to safer, personalized treatment decisions.