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 Park; Do Sun Lim

doi:10.3390/cells10102741

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 journal › Article › peer-review

2 Citations (Scopus)

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 language	English
Article number	2741
Journal	Cells
Volume	10
Issue number	10
DOIs	https://doi.org/10.3390/cells10102741
Publication status	Published - 2021 Oct

Keywords

Cardiac
Cytokines
Differentiation
Hypoxia
Pluripotent stem cells

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cells10102741

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Choi, S. C., Seo, H. R., Cui, L. H., Song, M. H., Noh, J. M., Kim, K. S., Choi, J. H., Kim, J. H., Park, C. Y., Joo, H. J., Hong, S. J., Ko, T. H., Choi, J. I., Kim, H. J., Kim, J. H., Paek, S. H., Park, J. N., Kim, D. H., Jang, Y., ... Lim, D. S. (2021). Modeling hypoxic stress in vitro using human embryonic stem cells derived cardiomyocytes matured by fgf4 and ascorbic acid treatment. Cells, 10(10), [2741]. https://doi.org/10.3390/cells10102741

Choi, SC, Seo, HR, Cui, LH, Song, MH, Noh, JM, Kim, KS, Choi, JH, Kim, JH, Park, CY, Joo, HJ, Hong, SJ, Ko, TH, Choi, JI, Kim, HJ, Kim, JH, Paek, SH, Park, JN, Kim, DH, Jang, Y, Park, Y & Lim, DS 2021, 'Modeling hypoxic stress in vitro using human embryonic stem cells derived cardiomyocytes matured by fgf4 and ascorbic acid treatment', Cells, vol. 10, no. 10, 2741. https://doi.org/10.3390/cells10102741

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

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.",

keywords = "Cardiac, Cytokines, Differentiation, Hypoxia, Pluripotent stem cells",

author = "Choi, {Seung Cheol} and Seo, {Ha Rim} and Cui, {Long Hui} and Song, {Myeong Hwa} and Noh, {Ji Min} and Kim, {Kyung Seob} and Choi, {Ji Hyun} and Kim, {Jong Ho} and Park, {Chi Yeon} and Joo, {Hyung Joon} and Hong, {Soon Jun} and Ko, {Tae Hee} and Choi, {Jong Il} and Kim, {Hyo Jin} and Kim, {Jong Hoon} and Paek, {Se Hwan} and Park, {Ji Na} and Kim, {Dong Hyung} and Yongjun Jang and Yongdoo Park and Lim, {Do Sun}",

note = "Funding Information: Funding: This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT); NRF-2016M3A9B6947892 (to Y.P.), and by the NRF grants funded by the Korea government; NRF-2015R1D1A1A01060473 (to S.-C.C.) and NRF-2018R1D1A1B07050742 (to S.-C.C.). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = oct,

doi = "10.3390/cells10102741",

language = "English",

volume = "10",

journal = "Cells",

issn = "2073-4409",

publisher = "MDPI Multidisciplinary Digital Publishing Institute",

number = "10",

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TY - JOUR

T1 - Modeling hypoxic stress in vitro using human embryonic stem cells derived cardiomyocytes matured by fgf4 and ascorbic acid treatment

AU - Choi, Seung Cheol

AU - Seo, Ha Rim

AU - Cui, Long Hui

AU - Song, Myeong Hwa

AU - Noh, Ji Min

AU - Kim, Kyung Seob

AU - Choi, Ji Hyun

AU - Kim, Jong Ho

AU - Park, Chi Yeon

AU - Joo, Hyung Joon

AU - Hong, Soon Jun

AU - Ko, Tae Hee

AU - Choi, Jong Il

AU - Kim, Hyo Jin

AU - Kim, Jong Hoon

AU - Paek, Se Hwan

AU - Park, Ji Na

AU - Kim, Dong Hyung

AU - Jang, Yongjun

AU - Park, Yongdoo

AU - Lim, Do Sun

N1 - Funding Information: Funding: This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT); NRF-2016M3A9B6947892 (to Y.P.), and by the NRF grants funded by the Korea government; NRF-2015R1D1A1A01060473 (to S.-C.C.) and NRF-2018R1D1A1B07050742 (to S.-C.C.). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/10

Y1 - 2021/10

N2 - 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.

AB - 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.

KW - Cardiac

KW - Cytokines

KW - Differentiation

KW - Hypoxia

KW - Pluripotent stem cells

UR - http://www.scopus.com/inward/record.url?scp=85116966851&partnerID=8YFLogxK

U2 - 10.3390/cells10102741

DO - 10.3390/cells10102741

M3 - Article

C2 - 34685725

AN - SCOPUS:85116966851

SN - 2073-4409

VL - 10

JO - Cells

JF - Cells

IS - 10

M1 - 2741

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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