Modeling Hypoxic Stress In Vitro Using Human Embryonic Stem Cells Derived Cardiomyocytes Matured by FGF4 and Ascorbic Acid Treatment
Seung-Cheol Choi,
Ha-Rim Seo,
Long-Hui Cui,
Myeong-Hwa Song,
Ji-Min Noh,
Kyung-Seob Kim,
Ji-Hyun Choi,
Jong-Ho Kim,
Chi-Yeon Park,
Hyung Joon Joo,
Soon Jun Hong,
Tae Hee Ko,
Jong-Il Choi,
Hyo Jin Kim,
Jong-Hoon Kim,
Se-Hwan Paek,
Ji-Na Park,
Dong-Hyung Kim,
Yongjun Jang,
Yongdoo Park,
Do-Sun Lim
Affiliations
Seung-Cheol Choi
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Ha-Rim Seo
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Long-Hui Cui
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Myeong-Hwa Song
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Ji-Min Noh
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Kyung-Seob Kim
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Ji-Hyun Choi
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Jong-Ho Kim
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Chi-Yeon Park
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Hyung Joon Joo
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Soon Jun Hong
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Tae Hee Ko
Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02841, Korea
Jong-Il Choi
Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02841, Korea
Hyo Jin Kim
Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea
Jong-Hoon Kim
Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea
Se-Hwan Paek
R&D Center for Companion Diagnostic, SOL Bio Corporation, Suite 510, 27, Seongsui-ro7-gil, Seongdong-gu, Seoul 04780, Korea
Ji-Na Park
Abbott Diagnostics Korea Inc., 65 Borahagal-ro, Yongin 17099, Korea
Dong-Hyung Kim
Korea Research Institute of Standards and Science, 267 Gajeong-ro, Yuseong-gu, Deajeon 34113, Korea
Yongjun Jang
Department of Biomedical Sciences, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Yongdoo Park
Department of Biomedical Sciences, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
Do-Sun Lim
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
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.
