| Autor: |
Stern, Brett, Monteleone, Peter, Zoldan, Janet |
| Zdroj: |
Journal of Biomedical Materials Research, Part A; Apr2024, Vol. 112 Issue 4, p524-533, 10p |
| Abstrakt: |
With new daily discoveries about the long‐term impacts of COVID‐19, there is a clear need to develop in vitro models that can be used to better understand the pathogenicity and impact of COVID‐19. Here, we demonstrate the utility of developing a model of endothelial dysfunction that utilizes human induced pluripotent stem cell‐derived endothelial progenitors encapsulated in collagen hydrogels to study the effects of COVID‐19 on the endothelium. These cells form capillary‐like vasculature within 1 week after encapsulation and treating these cell‐laden hydrogels with SARS‐CoV‐2 spike protein resulted in a significant decrease in the number of vessel‐forming cells as well as vessel network connectivity quantified by our computational pipeline. This vascular dysfunction is a unique phenomenon observed upon treatment with SARS‐CoV‐2 SP and is not seen upon treatment with other coronaviruses, indicating that these effects were specific to SARS‐CoV‐2. We show that this vascular dysfunction is caused by an increase in inflammatory cytokines, associated with the COVID‐19 cytokine storm, released from SARS‐CoV‐2 spike protein treated endothelial cells. Following treatment with the corticosteroid dexamethasone, we were able to prevent SARS‐CoV‐2 spike protein‐induced endothelial dysfunction. Our results highlight the importance of understanding the interactions between SARS‐CoV‐2 spike protein and the endothelium and show that even in the absence of immune cells, the proposed 3D in vitro model for angiogenesis can reproduce COVID‐19‐induced endothelial dysfunction seen in clinical settings. This model represents a significant step in creating physiologically relevant disease models to further study the impact of long COVID and potentially identify mitigating therapeutics. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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