Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Platform to Study SARS-CoV-2 Related Myocardial Injury

Chun-Ka Wong; Hayes Kam-Hei Luk; Wing-Hon Lai; Yee-Man Lau; Ricky Ruiqi Zhang; Antonio Cheuk-Pui Wong; George Chi-Shing Lo; Kwok-Hung Chan; Ivan Fan-Ngai Hung; Hung-Fat Tse; Patrick Chiu-Yat Woo; Susanna Kar-Pui Lau; Chung-Wah Siu

doi:10.1253/circj.CJ-20-0881

Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Platform to Study SARS-CoV-2 Related Myocardial Injury

Circ J. 2020 Oct 23;84(11):2027-2031. doi: 10.1253/circj.CJ-20-0881. Epub 2020 Sep 26.

Affiliations

¹ Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong.
² Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong.
³ Infectious Disease Division, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong.

PMID: 32981925
DOI: 10.1253/circj.CJ-20-0881

Abstract

Background: SARS-CoV-2 infection is associated with myocardial injury, but there is a paucity of experimental platforms for the condition.Methods and Results:Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected by SARS-CoV-2 for 3 days ceased beating and exhibited cytopathogenic changes with reduced viability. Active viral replication was evidenced by an increase in supernatant SARS-CoV-2 and the presence of SARS-CoV-2 nucleocaspid protein within hiPSC-CMs. Expressions of BNP, CXCL1, CXCL2, IL-6, IL-8 and TNF-α were upregulated, while ACE2 was downregulated.

Conclusions: Our hiPSC-CM-based in-vitro SARS-CoV-2 myocarditis model recapitulated the cytopathogenic effects and cytokine/chemokine response. It could be exploited as a drug screening platform.

Keywords: COVID-19; Myocarditis; SARS-CoV-2; Stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme 2
Betacoronavirus / genetics
Betacoronavirus / metabolism*
COVID-19
Cell Survival
Cells, Cultured
Coronavirus Infections / complications*
Coronavirus Infections / metabolism
Coronavirus Infections / virology
Coronavirus Nucleocapsid Proteins
Cytokines / metabolism
Cytopathogenic Effect, Viral
Drug Evaluation, Preclinical / methods
Humans
Induced Pluripotent Stem Cells / metabolism
Induced Pluripotent Stem Cells / virology*
Myocarditis / complications*
Myocarditis / metabolism
Myocarditis / virology
Myocytes, Cardiac / metabolism
Myocytes, Cardiac / virology*
Nucleocapsid Proteins / metabolism
Pandemics
Peptidyl-Dipeptidase A / metabolism
Phosphoproteins
Pneumonia, Viral / complications*
Pneumonia, Viral / metabolism
Pneumonia, Viral / virology
Reverse Transcriptase Polymerase Chain Reaction
SARS-CoV-2
Virus Replication

Substances

Coronavirus Nucleocapsid Proteins
Cytokines
Nucleocapsid Proteins
Phosphoproteins
nucleocapsid phosphoprotein, SARS-CoV-2
Peptidyl-Dipeptidase A
ACE2 protein, human
Angiotensin-Converting Enzyme 2