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- Title
Modeling Hypoxic Stress In Vitro Using Human Embryonic Stem Cells Derived Cardiomyocytes Matured by FGF4 and Ascorbic Acid Treatment.
- Authors
Choi, Seung-Cheol; Seo, Ha-Rim; Cui, Long-Hui; Song, Myeong-Hwa; Noh, Ji-Min; Kim, Kyung-Seob; Choi, Ji-Hyun; Kim, Jong-Ho; Park, Chi-Yeon; Joo, Hyung Joon; Hong, Soon Jun; Ko, Tae Hee; Choi, Jong-Il; Kim, Hyo Jin; Kim, Jong-Hoon; Paek, Se-Hwan; Park, Ji-Na; Kim, Dong-Hyung; Jang, Yongjun; Park, Yongdoo
- Abstract
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.
- Subjects
HUMAN embryonic stem cells; EMBRYONIC stem cells; PLURIPOTENT stem cells; HEART disease diagnosis; HUMAN stem cells; MYOCARDIAL infarction; VITAMIN C
- Publication
Cells (2073-4409), 2021, Vol 10, Issue 10, p2741
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells10102741