Advances in heart slice culture for translational research

Drug-induced cardiotoxicity remains a major cause of late-stage clinical trial failure and postmarketing drug withdrawal, underscoring the limitations of traditional in vitro screening platforms.While hERG assays, isolated adult cardiomyocytes, and human induced pluripotent stem cell-derived cardiomyocytes have improved early safety assessment, these systems fail to fully recapitulate the structural, multicellular, and biomechanical complexity of native myocardium.Precision-cut heart slice technology has emerged as a powerful organotypic model that preserves intact cellular architecture, extracellular matrix composition, and physiological cell-cell interactions.Recent advances integrating biomimetic electromechanical stimulation, controlled preload and afterload conditions, optimized media formulations, oxygenation strategies, and perfusion bioreactors have substantially extended tissue viability and functional stability ex vivo.These improvements have enabled the maintenance of contractile force, sarcomere integrity, metabolic activity, and transcriptional maturity for up to two weeks in culture.Importantly, heart slices demonstrate superior sensitivity in detecting clinically relevant cardiotoxic effects compared to stem cell-based systems, particularly for oncology therapeutics.Emerging applications include modeling hypertrophy, fibrosis, arrhythmogenic cardiomyopathy, gene therapy vector optimization, and evaluation of cardioprotective strategies.Platforms such as MyoDish, stretcher-based systems, and biomimetic cardiac tissue culture models represent distinct yet converging technological approaches that balance physiological rigor with scalability.Collectively, precision-cut heart slices bridge the translational gap between reductionist cell culture models and in vivo studies.Continued standardization, integration of dynamic mechanical conditioning, and expansion towards modular high-throughput systems are expected to further position this technology as a central platform for cardiotoxicity screening and translational cardiovascular research.