Human cardiovascular organoids: Biomedical applications and ethical challenges

Abstract

Cardiovascular disease (CVD) remains the leading cause of global mortality, yet traditional in vitro and animal models often fail to recapitulate the integrated structural, cellular, and functional complexity of the human heart. Recent advances in human pluripotent stem cell technology, developmental bioengineering, and microphysiological systems have enabled the development of diverse three-dimensional cardiac tissue models, including self-organizing cardiovascular organoids and engineered cardiac platforms, three-dimensional constructs that partially recapitulate key myocardial features. These platforms facilitate mechanistic and disease-relevant modelling of congenital and acquired cardiac disorders, allow interrogation of arrhythmogenic mechanisms, and reproduce pathophysiological processes such as ischemia–reperfusion injury, fibrotic remodelling, and inflammatory cardiomyopathy with increasing physiological relevance. In translational contexts, these models are emerging as valuable tools in drug discovery pipelines, enabling high-throughput cardiotoxicity assessment and supporting regenerative medicine strategies, thereby bridging mechanistic research with preclinical validation. Integration with cutting-edge modalities—such as single-cell and spatial multi-omics, CRISPR-based genome editing, synthetic biology circuits, and artificial intelligence-driven phenomics further enhances their maturation and predictive accuracy, although their clinical applicability remains under active investigation. Despite these advances, challenges including batch-to-batch variability, limited vascularization, metabolic immaturity, and incomplete immune system incorporation continue to constrain physiological fidelity. Additionally, ethical and regulatory considerations spanning donor consent, genetic data privacy, biobanking governance, and model-specific translational and societal implications remain critical for responsible innovation. This review presents a comprehensive synthesis of current cardiovascular organoid research, highlights emerging biomedical applications, and provides a critical perspective on the ethical frameworks essential for advancing the field responsibly.