{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T01:45:19Z","timestamp":1785375919958,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bio &amp; Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT)","award":["NRF-2016M3A9B6947892, NRF-2015R1D1A1A01060473, NRF-2018R1D1A1B07050742"],"award-info":[{"award-number":["NRF-2016M3A9B6947892, NRF-2015R1D1A1A01060473, NRF-2018R1D1A1B07050742"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\u2013cardiogenic 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.<\/jats:p>","DOI":"10.3390\/cells10102741","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T09:10:49Z","timestamp":1634202649000},"page":"2741","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Modeling Hypoxic Stress In Vitro Using Human Embryonic Stem Cells Derived Cardiomyocytes Matured by FGF4 and Ascorbic Acid Treatment"],"prefix":"10.3390","volume":"10","author":[{"given":"Seung-Cheol","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"},{"name":"R&D Center for Companion Diagnostic, SOL Bio Corporation, Suite 510, 27, Seongsui-ro7-gil, Seongdong-gu, Seoul 04780, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha-Rim","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"},{"name":"Division of Drug Efficacy Evaluation, New Drug Development Center, Osong Medical Innovation Foundation, 123, Osongsaengmyeong-ro, Osong-eup, Heungdeok-gu, Cheonju-si 28160, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long-Hui","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeong-Hwa","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Min","family":"Noh","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Seob","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hyun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1309-0821","authenticated-orcid":false,"given":"Jong-Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Yeon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Joon","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-6678","authenticated-orcid":false,"given":"Soon Jun","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hee","family":"Ko","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6617-508X","authenticated-orcid":false,"given":"Jong-Il","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3419-0538","authenticated-orcid":false,"given":"Jong-Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se-Hwan","family":"Paek","sequence":"additional","affiliation":[{"name":"R&D Center for Companion Diagnostic, SOL Bio Corporation, Suite 510, 27, Seongsui-ro7-gil, Seongdong-gu, Seoul 04780, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Na","family":"Park","sequence":"additional","affiliation":[{"name":"Abbott Diagnostics Korea Inc., 65 Borahagal-ro, Yongin 17099, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Hyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Korea Research Institute of Standards and Science, 267 Gajeong-ro, Yuseong-gu, Deajeon 34113, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0508-4341","authenticated-orcid":false,"given":"Yongjun","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3822-4651","authenticated-orcid":false,"given":"Yongdoo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do-Sun","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1161\/CIRCRESAHA.114.300558","article-title":"Engineering adolescence: Maturation of human pluripotent stem cell-derived 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