tetano
Editor, Senior Moderator
J Biomed Mater Res A
. 2023 Apr 8.
doi: 10.1002/jbm.a.37543. Online ahead of print.
SARS-CoV-2 spike protein induces endothelial dysfunction in 3D engineered vascular networks
Brett Stern[SUP] 1 [/SUP], Peter Monteleone[SUP] 2 3 [/SUP], Janet Zoldan[SUP] 1 [/SUP]
Affiliations
Abstract
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.
Keywords: 3D in vitro models; COVID-19; angiogenesis; induced pluripotent stem cells.
. 2023 Apr 8.
doi: 10.1002/jbm.a.37543. Online ahead of print.
SARS-CoV-2 spike protein induces endothelial dysfunction in 3D engineered vascular networks
Brett Stern[SUP] 1 [/SUP], Peter Monteleone[SUP] 2 3 [/SUP], Janet Zoldan[SUP] 1 [/SUP]
Affiliations
- PMID: 37029655
- DOI: 10.1002/jbm.a.37543
Abstract
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.
Keywords: 3D in vitro models; COVID-19; angiogenesis; induced pluripotent stem cells.