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Review of "SARS-CoV-2 Infection of Human Pluripotent Stem Cell-derived Vascular Cells Reveals Smooth Muscle Cells as Key Mediators of Vascular Pathology during Infection"

Reviewers: H J Chen & K Zhang (University of Chicago) | 📗📗📗📗◻️

Published onJul 02, 2024
Review of "SARS-CoV-2 Infection of Human Pluripotent Stem Cell-derived Vascular Cells Reveals Smooth Muscle Cells as Key Mediators of Vascular Pathology during Infection"
key-enterThis Pub is a Review of
SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection
SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection
Description

Summary Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events1. This prothrombotic state is considered a key factor in the increased risk of stroke, which has been observed clinically during both acute infection and long after symptoms have cleared2. Here we developed a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells, pericytes, and smooth muscle cells to recapitulate the vascular pathology associated with SARS-CoV-2 exposure. Our results demonstrate that perivascular cells, particularly smooth muscle cells (SMCs), are a specifically susceptible vascular target for SARS-CoV-2 infection. Utilizing RNA sequencing, we characterized the transcriptomic changes accompanying SARS-CoV-2 infection of SMCs, and endothelial cells (ECs). We observed that infected human SMCs shift to a pro-inflammatory state and increase the expression of key mediators of the coagulation cascade. Further, we showed human ECs exposed to the secretome of infected SMCs produce hemostatic factors that can contribute to vascular dysfunction, despite not being susceptible to direct infection. The findings here recapitulate observations from patient sera in human COVID-19 patients and provide mechanistic insight into the unique vascular implications of SARS-CoV-2 infection at a cellular level.

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Summary of Reviews: The reviewer found the study reliable, highlighting its model of SARS-CoV-2 vascular pathology using stem cell-derived cells. They noted the findings on smooth muscle cells' vulnerability and pro-inflammatory response to infection, aligning with COVID-19 patient data. While considering the model valuable, the reviewer suggested improvements, including updating the literature review, comparing with other models, validating protocols, and deepening pathway analysis.

Reviewer 1 (Huanhuan Joyce C…) | 📗📗📗📗◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

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