Modeling hypoxic stress in vitro using human embryonic stem cells derived cardiomyocytes matured by fgf4 and ascorbic acid treatment

Seung Cheol Choi, 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 ParkDo Sun Lim

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number2741
JournalCells
Volume10
Issue number10
DOIs
Publication statusPublished - 2021 Oct

Keywords

  • Cardiac
  • Cytokines
  • Differentiation
  • Hypoxia
  • Pluripotent stem cells

ASJC Scopus subject areas

  • Medicine(all)

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