Modeling acute myocardial infarction in vitro using mature and ventricular hESC-derived cardiomyocytes by FGF4 and ascorbic acid treatment. Modeling acute myocardial infarction in vitro using mature and ventricular hESC-derived cardiomyocytes by FGF4 and ascorbic acid treatment

hPSC-CMs resemble immature embryonic or fetal CMs rather than mature adult CMs, and have limitations in disease modeling and pharmacological studies. Therefore, hPSCs-derived mature and ventricular CMs are required for more accurate in vitro modeling of adult-onset cardiac disease and drug discovery. FGF4+AA-treated hESC-CMs robustly released acute myocardial infarction (AMI) biomarkers (cTnI, CK-MB, and myoglobin) into culture medium in response to hypoxic injury. Hypoxia-responsive genes related to cellular responses to glycolytic processes, oxygen levels, HIF-1 signaling, apoptotic processes, and regulation of cell death including potential cardiac biomarkers proved in clinical studies in the diagnosis and prognosis of coronary artery diseases were induced in FGF4+AA-treated hESC-CMs in response to hypoxia based on transcriptome analyses. Overall design: RNA profiles of normoxia- and hypoxia-treated BG01 hESC-CMs for 24 hr after treatment with FGF4+AA between days 5 and 15 of differentiation