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

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.

Inhibition of SARS-CoV-2 infection in human cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoskeleton architecture and contractility

“…Along with monocytes and fibroblasts, cardiomyocytes are also an important source of cytokines during events such as heart failure (Aoyagi and Matsui, 2012). Here, we showed that IL-6, IL-8 and TNF-α release is stimulated in hiPSC-CMs in response to SARS-CoV-2 infection, complementing previous data on increased mRNA levels of these cytokines (Wong et al, 2020). Elevated levels of IL-6 are strongly correlated with cardiac damage and heart failure in rodent models (Janssen et al, 2005; Jug et al, 2009).…”

The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications

“…Of note, SARS-CoV-2 invasion exhibited cytopathogenic effects on iPSC- cardiomyocytes, inducing cell rounding, formation of grapelike clumps, and complete destruction of cell monolayers together with irreversible pyknotic cell shrinkage, which terminates in myocardial injuries. Furthermore, an array of cytokines and chemokines (IL-6, IL-8, tumor necrosis factor (TNF)-α, CXCL1 and CXCL2) from iPSC-cardiomyocytes were released to assist further injury [ 261 ]. Recently employed drugs such as chloroquine (CQ) and azithromycin (AZM) to treat SARS-CoV-2 infection, were also tested on the human embryonic stem cell derived cardiomyocytes to investigate the drug induced cardiotoxicity, which reinforced the findings obtained from clinical data [ 262 ].…”

Transcriptome profiling of different types of human respiratory tract cells infected by SARS-CoV-2 highlight an unique role for inflammatory and interferon response

“…The clinical picture of COVID-19 patients are characterized by an over-exuberant immune response with lung lymphomononuclear cells infiltration and proliferation that may account for tissue damage more than the direct effect of viral replication (Azkur et al 2020;Blanco-Melo et al 2020;Yang et al 2020). Evidence also showed that SARS-CoV-2 infects human respiratory tract cells, prompting inflammation and tissue damage/loss as well as in other different cell types (Wong et al 2020). Despite recent advances, little is known about the pathways involved in viral pathogenesis (Ziegler et al 2020).…”