Cardiomyocytes derived from pluripotent stem cells hold promise for applying cardiac pharmacology studies and regeneration therapy. One of the most significant issues for their biomedical applications is the immaturity of pluripotent stem cell-derived cardiomyocytes. Cardiomyocytes derived from pluripotent stem cells tend to halt their maturation and maintain an embryonic state during in vitro cultivation. Thus far, our efforts have been focused on inducing the maturation of the cardiomyocytes. Using the reporter iPSCs of cardiomyocyte maturation, we conducted a high throughput screening and identified an ERRγ agonist that induced upregulation of TNNI3, a marker for mature cardiomyocytes.
Furthermore, the ERRγ agonist induced comprehensive maturation of iPSC-derived cardiomyocytes, including electrophysiological properties, mitochondria functions, sarcomere structures, and T tubule formation. We also confirmed that this compound-based maturation can be applied to generate 3D mature engineered heart tissue by combining mechanical stimulation. The mature engineered heart tissue can be used for toxicology studies to assess the cardiotoxicity of anticancer drugs and model cardiac diseases to investigate the disease mechanism.
Collectively, the generation of mature cardiac tissues will help efficiently establish models for cardiac pharmacology studies.