Using Cardiovascular Cells from Human Pluripotent Stem Cells for COVID-19 Research: Why the Heart Fails

Yiangou, Loukia; Davis, Richard P.; Mummery, Christine L.

doi:10.1016/j.stemcr.2020.11.003

Cited by 31 publications

(32 citation statements)

References 95 publications

(130 reference statements)

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“…According to COVID-19, this model seems to be extremely beneficial for the viral infections investigations. It even allows testing all kinds of therapies, including the antibody treatment and anti-inflammatory drugs [ 59 ].…”

Section: Ace2 Is An Adjacent Elementmentioning

confidence: 99%

ACE2 Is an Adjacent Element of Atherosclerosis and COVID-19 Pathogenesis

Poznyak

Bezsonov

Eid

et al. 2021

IJMS

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COVID-19 is a highly contagious new infection caused by the single-stranded RNA Sars-CoV-2 virus. For the first time, this infection was recorded in December 2019 in the Chinese province of Wuhan. The virus presumably crossed the interspecies barrier and passed to humans from a bat. Initially, the disease was considered exclusively in the context of damage to the respiratory system, but it quickly became clear that the disease also entails serious consequences from various systems, including the cardiovascular system. Among these consequences are myocarditis, myocardial damage, subsequent heart failure, myocardial infarction, and Takotsubo syndrome. On the other hand, clinical data indicate that the presence of chronic diseases in a patient aggravates the course and outcome of coronavirus infection. In this context, the relationship between COVID-19 and atherosclerosis, a condition preceding cardiovascular disease and other disorders of the heart and blood vessels, is particularly interesting. The renin-angiotensin system is essential for the pathogenesis of both coronavirus disease and atherosclerosis. In particular, it has been shown that ACE2, an angiotensin-converting enzyme 2, plays a key role in Sars-CoV-2 infection due to its receptor activity. It is noteworthy that this enzyme is important for the normal functioning of the cardiovascular system. Disruptions in its production and functioning can lead to various disorders, including atherosclerosis.

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Section: Ace2 Is An Adjacent Elementmentioning

confidence: 99%

ACE2 Is an Adjacent Element of Atherosclerosis and COVID-19 Pathogenesis

Poznyak

Bezsonov

Eid

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…Common models used to study SARS-CoV-2 include immortalized cell lines and genetically modified mice [ 75 , 76 ]. Although these models have demonstrated significant utility in studying the mechanisms of viral entry and replication, they fail to effectively mimic the physiological conditions of different tissue systems in humans [ 77 ]. Since SARS-CoV-2 infects multiple cell types across different tissues, hPSC models may serve as a good platform to comprehensively study SARS-CoV-2 infection.…”

Section: Human Stem Cell-based Modelsmentioning

confidence: 99%

Human Stem Cell Models of SARS-CoV-2 Infection in the Cardiovascular System

Ernzen

Trask

Peeples

et al. 2021

Stem Cell Rev and Rep

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The virus responsible for coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over 190 million people to date, causing a global pandemic. SARS-CoV-2 relies on binding of its spike glycoprotein to angiotensin-converting enzyme 2 (ACE2) for infection. In addition to fever, cough, and shortness of breath, severe cases of SARS-CoV-2 infection may result in the rapid overproduction of pro-inflammatory cytokines. This overactive immune response is known as a cytokine storm, which leads to several serious clinical manifestations such as acute respiratory distress syndrome and myocardial injury. Cardiovascular disorders such as acute coronary syndrome (ACS) and heart failure not only enhance disease progression at the onset of infection, but also arise in hospitalized patients with COVID-19. Tissue-specific differentiated cells and organoids derived from human pluripotent stem cells (hPSCs) serve as an excellent model to address how SARS-CoV-2 damages the lungs and the heart. In this review, we summarize the molecular basis of SARS-CoV-2 infection and the current clinical perspectives of the bidirectional relationship between the cardiovascular system and viral progression. Furthermore, we also address the utility of hPSCs as a dynamic model for SARS-CoV-2 research and clinical translation. Graphical abstract

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“…Although the dominant pathology of COVID-19 involves the respiratory system, 20%-30% of COVID-19 patients experience severe cardiovascular damage, which emerged as a major indicator of poor prognosis [8,14]. Moreover, patients with pre-existing heart complications are more likely to develop severe illness and have higher risk of death compared with patients without co-morbidities [14,15]. Therefore, a COVID-Gu et al / vaccination.…”

Section: The Ongoing Pandemic Of Coronavirus Disease 19 (Covid-19) Caused By a Coronavirus Sars-mentioning

confidence: 99%

Ad5-spike COVID-19 vaccine does not aggravate heart damage after ischemic injury

Chen

Meng

et al. 2021

Preprint

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Hopes for a COVID-19 vaccine are now a reality. The spike protein of SARS-CoV-2, which majorly binds to the host receptor ACE2 for cell entry, is used by most of the COVID-19 vaccine candidates as a choice of antigen. ACE2 is highly expressed in the heart and is known to be protective in multiple organs. Interaction of spike with ACE2 has been reported to reduce ACE2 expression and affect ACE2-mediated signal transduction in the heart. However, whether a spike-encoding vaccine will aggravate myocardial damage after a heart attack via affecting ACE2 remains unclear. Therefore, for patients with or at risk of heart diseases, questions arise around the safety of the spike-based vaccines. Here, we demonstrate that ACE2 is up-regulated and protective in the injured mouse heart after myocardial ischemia/reperfusion (I/R). Infecting human cardiomyocyte, smooth muscle cells, endothelial cells, and cardiac fibroblasts with a recombinant adenovirus type-5 vectored COVID-19 vaccine expressing the spike protein (AdSpike) does not affect cell survival and cardiomyocyte function, whether the cells are subjected to hypoxia-reoxygenation injury or not. This observation is further confirmed in human engineered heart tissues. Furthermore, AdSpike vaccination does not aggravate heart damage in wild-type or humanized ACE2 mice after I/R injury, even at a dose that is ten-fold higher as used in human. This study represents the first systematic evaluation of the safety of a leading COVID-19 vaccine under a disease context and may provide important information to ensure maximal protection from COVID-19 in patients with or at risk of heart diseases.

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Using Cardiovascular Cells from Human Pluripotent Stem Cells for COVID-19 Research: Why the Heart Fails

Cited by 31 publications

References 95 publications

ACE2 Is an Adjacent Element of Atherosclerosis and COVID-19 Pathogenesis

ACE2 Is an Adjacent Element of Atherosclerosis and COVID-19 Pathogenesis

Human Stem Cell Models of SARS-CoV-2 Infection in the Cardiovascular System

Ad5-spike COVID-19 vaccine does not aggravate heart damage after ischemic injury

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