Maturation of human induced pluripotent stem cell-derived cardiomyocytes for modeling hypertrophic cardiomyopathy

Rationale: Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they are immature, which is a barrier to modeling adult-onset cardiovascular disease. Objective: We sought to develop a simple method which could drive cultured hiPSC-CMs towards maturity across a number of phenotypes. Methods and results: Cells were cultured in fatty acid-based media and plated on micropatterned surfaces to promote alignment and elongation. These cells display many characteristics of adult human cardiomyocytes, including elongated cell morphology, enhanced maturity of sarcomeric structures, metabolic behavior, and increased myofibril contractile force. Most notably, hiPSC-CMs cultured under optimal maturity-inducing conditions recapitulate the pathological hypertrophy caused by either a pro-hypertrophic agent or genetic mutations. Conclusions: The more mature hiPSC-CMs produced by the methods described here will serve as a useful in vitro platform for characterizing cardiovascular disease.