Human cardiac organoids to model COVID-19 cytokine storm induced cardiac injuries
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Human cardiac organoids to model COVID-19 cytokine storm induced cardiac injuries. / Arhontoulis, Dimitrios C; Kerr, Charles M; Richards, Dylan; Tjen, Kelsey; Hyams, Nathaniel; Jones, Jefferey A; Deleon-Pennell, Kristine; Menick, Donald; Bräuninger, Hanna; Lindner, Diana; Westermann, Dirk; Mei, Ying.
in: J TISSUE ENG REGEN M, Jahrgang 16, Nr. 9, 09.2022, S. 799-811.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung
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TY - JOUR
T1 - Human cardiac organoids to model COVID-19 cytokine storm induced cardiac injuries
AU - Arhontoulis, Dimitrios C
AU - Kerr, Charles M
AU - Richards, Dylan
AU - Tjen, Kelsey
AU - Hyams, Nathaniel
AU - Jones, Jefferey A
AU - Deleon-Pennell, Kristine
AU - Menick, Donald
AU - Bräuninger, Hanna
AU - Lindner, Diana
AU - Westermann, Dirk
AU - Mei, Ying
N1 - © 2022 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd.
PY - 2022/9
Y1 - 2022/9
N2 - Acute cardiac injuries occur in 20%-25% of hospitalized COVID-19 patients. 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 thus provide a defined and robust 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.
AB - Acute cardiac injuries occur in 20%-25% of hospitalized COVID-19 patients. 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 thus provide a defined and robust 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.
KW - COVID-19/complications
KW - Cytokine Release Syndrome/virology
KW - Cytokines/metabolism
KW - Heart Diseases/virology
KW - Humans
KW - Models, Biological
KW - Organoids
U2 - 10.1002/term.3327
DO - 10.1002/term.3327
M3 - SCORING: Journal article
C2 - 35689600
VL - 16
SP - 799
EP - 811
JO - J TISSUE ENG REGEN M
JF - J TISSUE ENG REGEN M
SN - 1932-6254
IS - 9
ER -