Modeling Hypoxic Stress In Vitro Using Human Embryonic Stem Cells Derived Cardiomyocytes Matured by FGF4 and Ascorbic Acid Treatment.
Seung-Cheol ChoiHa-Rim SeoLong-Hui CuiMyeong-Hwa SongJi-Min NohKyung-Seob KimJi-Hyun ChoiJong-Ho KimChi-Yeon ParkHyung Joon JooSoon Jun HongTae Hee KoJong-Il ChoiHyo Jin KimJong-Hoon KimSe-Hwan PaekJi-Na ParkDong-Hyung KimYongjun JangYong-Doo ParkDo-Sun LimPublished in: Cells (2021)
Mature cardiomyocytes (CMs) obtained from human pluripotent stem cells (hPSCs) have been required for more accurate in vitro modeling of adult-onset cardiac disease and drug discovery. Here, we found that FGF4 and ascorbic acid (AA) induce differentiation of BG01 human embryonic stem cell-cardiogenic mesoderm cells (hESC-CMCs) into mature and ventricular CMs. Co-treatment of BG01 hESC-CMCs with FGF4+AA synergistically induced differentiation into mature and ventricular CMs. FGF4+AA-treated BG01 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 and potential cardiac biomarkers proved in the diagnosis and prognosis of coronary artery diseases were induced in FGF4+AA-treated BG01 hESC-CMs in response to hypoxia based on transcriptome analyses. This study demonstrates that it is feasible to model hypoxic stress in vitro using hESC-CMs matured by soluble factors.
Keyphrases
- pluripotent stem cells
- endothelial cells
- high glucose
- acute myocardial infarction
- left ventricular
- coronary artery
- stem cells
- drug discovery
- heart failure
- induced pluripotent stem cells
- genome wide
- gene expression
- diabetic rats
- high resolution
- stress induced
- cell death
- percutaneous coronary intervention
- newly diagnosed
- drug induced
- acute coronary syndrome
- coronary artery disease
- cancer therapy
- climate change
- pulmonary hypertension