Human Living Myocardial Slices as a New Approach Methodology

Cardiovascular disease remains the leading cause of mortality worldwide, highlighting the need for predictive, human-relevant experimental models that improve translational success and reduce reliance on animal research. Human living myocardial slices (LMS) have emerged as a powerful new approach methodology (NAM), bridging the gap between simplified in vitro systems and clinically relevant human tissue. By preserving the native multicellular composition, extracellular matrix, and adult myocardial architecture, LMS retain key structural, mechanical, electrophysiological, and molecular properties of the human heart that are often lost in conventional cell culture models and not fully recapitulated by stem cell-derived platforms. Reviewed here are the historical development of cardiac slice technologies and the principles underlying modern human LMS preparation and biomimetic culture, enabling long-term functional maintenance of LMS. Diverse applications of LMS in translational cardiovascular research are summarised. By retaining patient-specific characteristics and clinically relevant responses, LMS provide a unique platform for investigating disease mechanisms, evaluating therapeutic interventions, and supporting precision medicine approaches. As access to human cardiac tissue expands and culture methodologies become increasingly standardized, LMS are well positioned to enhance translational success, accelerate cardiovascular drug development, and support the broader adoption of NAMs in biomedical research.