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

Autor: Ji-Na Park, Seung-Cheol Choi, Yongdoo Park, Ji-Hyun Choi, Soon Jun Hong, Jong-Hoon Kim, Hyojin Kim, Chi-Yeon Park, Dong-Hyung Kim, Long-Hui Cui, Jong Il Choi, Yongjun Jang, Tae Hee Ko, Kyung-Seob Kim, Myeong-Hwa Song, Ha-Rim Seo, Hyung Joon Joo, Ji-Min Noh, Jong-Ho Kim, Do Sun Lim, Se-Hwan Paek
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cells, Vol 10, Iss 2741, p 2741 (2021)
Cells
Volume 10
Issue 10
ISSN: 2073-4409
Popis: 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.
Databáze: OpenAIRE