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Human Cardiac Organoids to Model COVID-19 Cytokine Storm Induced Cardiac Injuries

Acute cardiac injuries occur in 20–25% of hospitalized COVID-19 patients. Despite urgent needs, there is a lack of 3D organotypic models of COVID-19 hearts for mechanistic studies and drug testing. Herein, we demonstrate that human cardiac organoids (hCOs) are a viable platform to model the cardiac...

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Autores principales: Arhontoulis, Dimitrios C, Kerr, Charles, Richards, Dylan, Tjen, Kelsey, Hyams, Nathaniel, Jones, Jefferey A., Deleon-Pennell, Kristine, Menick, Donald, Lindner, Diana, Westermann, Dirk, Mei, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820666/
https://www.ncbi.nlm.nih.gov/pubmed/35132419
http://dx.doi.org/10.1101/2022.01.31.478497
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author Arhontoulis, Dimitrios C
Kerr, Charles
Richards, Dylan
Tjen, Kelsey
Hyams, Nathaniel
Jones, Jefferey A.
Deleon-Pennell, Kristine
Menick, Donald
Lindner, Diana
Westermann, Dirk
Mei, Ying
author_facet Arhontoulis, Dimitrios C
Kerr, Charles
Richards, Dylan
Tjen, Kelsey
Hyams, Nathaniel
Jones, Jefferey A.
Deleon-Pennell, Kristine
Menick, Donald
Lindner, Diana
Westermann, Dirk
Mei, Ying
author_sort Arhontoulis, Dimitrios C
collection PubMed
description Acute cardiac injuries occur in 20–25% of hospitalized COVID-19 patients. Despite urgent needs, there is a lack of 3D organotypic models of COVID-19 hearts for mechanistic studies and drug testing. Herein, we demonstrate that human cardiac organoids (hCOs) are a viable platform to model the cardiac injuries caused by COVID-19 hyperinflammation. As IL-1β is an upstream cytokine and a core COVID-19 signature cytokine, it was used to stimulate hCOs to induce the release of a milieu of proinflammatory cytokines that mirror the profile of COVID-19 cytokine storm. The IL-1β treated hCOs recapitulated transcriptomic, structural, and functional signatures of COVID-19 hearts. The comparison of IL-1β treated hCOs with cardiac tissue from COVID-19 autopsies illustrated the critical roles of hyper-inflammation in COVID-19 cardiac insults and indicated the cardioprotective effects of endothelium. The IL-1β treated hCOs also provide a viable model to assess the efficacy and potential side effects of immunomodulatory drugs, as well as the reversibility of COVID-19 cardiac injuries at baseline and simulated exercise conditions.
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spelling pubmed-88206662022-02-08 Human Cardiac Organoids to Model COVID-19 Cytokine Storm Induced Cardiac Injuries Arhontoulis, Dimitrios C Kerr, Charles Richards, Dylan Tjen, Kelsey Hyams, Nathaniel Jones, Jefferey A. Deleon-Pennell, Kristine Menick, Donald Lindner, Diana Westermann, Dirk Mei, Ying bioRxiv Article Acute cardiac injuries occur in 20–25% of hospitalized COVID-19 patients. Despite urgent needs, there is a lack of 3D organotypic models of COVID-19 hearts for mechanistic studies and drug testing. Herein, we demonstrate that human cardiac organoids (hCOs) are a viable platform to model the cardiac injuries caused by COVID-19 hyperinflammation. As IL-1β is an upstream cytokine and a core COVID-19 signature cytokine, it was used to stimulate hCOs to induce the release of a milieu of proinflammatory cytokines that mirror the profile of COVID-19 cytokine storm. The IL-1β treated hCOs recapitulated transcriptomic, structural, and functional signatures of COVID-19 hearts. The comparison of IL-1β treated hCOs with cardiac tissue from COVID-19 autopsies illustrated the critical roles of hyper-inflammation in COVID-19 cardiac insults and indicated the cardioprotective effects of endothelium. The IL-1β treated hCOs also provide a viable model to assess the efficacy and potential side effects of immunomodulatory drugs, as well as the reversibility of COVID-19 cardiac injuries at baseline and simulated exercise conditions. Cold Spring Harbor Laboratory 2022-02-01 /pmc/articles/PMC8820666/ /pubmed/35132419 http://dx.doi.org/10.1101/2022.01.31.478497 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Arhontoulis, Dimitrios C
Kerr, Charles
Richards, Dylan
Tjen, Kelsey
Hyams, Nathaniel
Jones, Jefferey A.
Deleon-Pennell, Kristine
Menick, Donald
Lindner, Diana
Westermann, Dirk
Mei, Ying
Human Cardiac Organoids to Model COVID-19 Cytokine Storm Induced Cardiac Injuries
title Human Cardiac Organoids to Model COVID-19 Cytokine Storm Induced Cardiac Injuries
title_full Human Cardiac Organoids to Model COVID-19 Cytokine Storm Induced Cardiac Injuries
title_fullStr Human Cardiac Organoids to Model COVID-19 Cytokine Storm Induced Cardiac Injuries
title_full_unstemmed Human Cardiac Organoids to Model COVID-19 Cytokine Storm Induced Cardiac Injuries
title_short Human Cardiac Organoids to Model COVID-19 Cytokine Storm Induced Cardiac Injuries
title_sort human cardiac organoids to model covid-19 cytokine storm induced cardiac injuries
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820666/
https://www.ncbi.nlm.nih.gov/pubmed/35132419
http://dx.doi.org/10.1101/2022.01.31.478497
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