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

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, Yong Jun; Park, Yongdoo; Lim, Do-Sun

doi:10.3390/cells10102741

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

Choi, Seung-Cheol;
Seo, Ha-Rim;
Cui, Long-Hui;
Song, Myeong-Hwa;
Noh, Ji-Min;
... Kim, Jong-Ho;
... Park, Chi-Yeon;
... Joo, Hyung Joon;
... Hong, Soon Jun;
... Choi, Jong-Il;
... Park, Yongdoo;
... Lim, Do-Sun;
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초록

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.</p>

키워드

pluripotent stem cells; cytokines; cardiac; differentiation; hypoxia; ACUTE MYOCARDIAL-INFARCTION; CARDIAC DIFFERENTIATION; SELF-RENEWAL; MATURATION; BIOMARKER; TROPONIN; SERUM; PERFORMANCE; EXPRESSION; PROMOTES

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

저자: 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, Yong Jun; Park, Yongdoo; Lim, Do-Sun

DOI: 10.3390/cells10102741

발행일: 2021-10

유형: Article

저널명: Cells

권: 10

호: 10

언어: ENG

출판사: Multidisciplinary Digital Publishing Institute (MDPI)

발행국가: 스위스

ISSN: E 2073-4409