Cells · 2021
Modeling Hypoxic Stress In Vitro Using Human Embryonic Stem Cells Derived Cardiomyocytes Matured by FGF4 and Ascorbic Acid Treatment.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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, Lim Do-Sun
Аннотация
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.