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Article

Modeling Hypoxic Stress In Vitro Using Human Embryonic Stem Cells Derived Cardiomyocytes Matured by FGF4 and Ascorbic Acid Treatment

1
Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
2
R&D Center for Companion Diagnostic, SOL Bio Corporation, Suite 510, 27, Seongsui-ro7-gil, Seongdong-gu, Seoul 04780, Korea
3
Division of Drug Efficacy Evaluation, New Drug Development Center, Osong Medical Innovation Foundation, 123, Osongsaengmyeong-ro, Osong-eup, Heungdeok-gu, Cheonju-si 28160, Korea
4
Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02841, Korea
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Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea
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Abbott Diagnostics Korea Inc., 65 Borahagal-ro, Yongin 17099, Korea
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Korea Research Institute of Standards and Science, 267 Gajeong-ro, Yuseong-gu, Deajeon 34113, Korea
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Department of Biomedical Sciences, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Klaus-Dieter Schlüter
Cells 2021, 10(10), 2741; https://doi.org/10.3390/cells10102741
Received: 2 September 2021 / Revised: 8 October 2021 / Accepted: 11 October 2021 / Published: 14 October 2021
(This article belongs to the Collection Cardiomyocytes, Myocardial Hypertrophy, and Heart Failure)
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. View Full-Text
Keywords: pluripotent stem cells; cytokines; cardiac; differentiation; hypoxia pluripotent stem cells; cytokines; cardiac; differentiation; hypoxia
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MDPI and ACS Style

Choi, S.-C.; Seo, H.-R.; Cui, L.-H.; Song, M.-H.; Noh, J.-M.; Kim, K.-S.; Choi, J.-H.; Kim, J.-H.; Park, C.-Y.; Joo, H.J.; Hong, S.J.; Ko, T.H.; Choi, J.-I.; Kim, H.J.; Kim, J.-H.; Paek, S.-H.; Park, J.-N.; Kim, D.-H.; Jang, Y.; Park, Y.; Lim, D.-S. Modeling Hypoxic Stress In Vitro Using Human Embryonic Stem Cells Derived Cardiomyocytes Matured by FGF4 and Ascorbic Acid Treatment. Cells 2021, 10, 2741. https://doi.org/10.3390/cells10102741

AMA Style

Choi S-C, Seo H-R, Cui L-H, Song M-H, Noh J-M, Kim K-S, Choi J-H, Kim J-H, Park C-Y, Joo HJ, Hong SJ, Ko TH, Choi J-I, Kim HJ, Kim J-H, Paek S-H, Park J-N, Kim D-H, Jang Y, Park Y, Lim D-S. Modeling Hypoxic Stress In Vitro Using Human Embryonic Stem Cells Derived Cardiomyocytes Matured by FGF4 and Ascorbic Acid Treatment. Cells. 2021; 10(10):2741. https://doi.org/10.3390/cells10102741

Chicago/Turabian Style

Choi, Seung-Cheol, 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, and Do-Sun Lim. 2021. "Modeling Hypoxic Stress In Vitro Using Human Embryonic Stem Cells Derived Cardiomyocytes Matured by FGF4 and Ascorbic Acid Treatment" Cells 10, no. 10: 2741. https://doi.org/10.3390/cells10102741

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