Modeling heart failure by induced pluripotent stem cell-derived organoids.

Cardiac organoids replicate tissue complexity better than 2D models, making them ideal for studying diseases like heart failure (HF). This study developed scaffold-free cardiac organoids from induced pluripotent stem cells (iPSCs) to model HF in vitro. Gene expression analysis confirmed a cardiac phenotype, and endothelin-1 (ET-1) treatment induced HF-like features. Key findings include upregulation of HF markers (ANP, BNP, ACTA1), altered miRNA profiles, reduced contractility, and protein aggregation. Nutraceutical co-treatment mitigated these effects, highlighting the model's utility in understanding HF mechanisms and testing therapies. Overall design: small RNA-sequencing of scaffold-free cardiac organoids derived from induced pluripotent stem cells (iPSCs) treated or not with endothelin-1 (ET-1) as hypertrophic inducer.