Molecular and Cellular Biology and Pathobiology Program, Medical University of South Carolina, Charleston, South Carolina, USA.
Bioengineering Department, Clemson University, Charleston, SC, USA.
J Tissue Eng Regen Med. 2022 Sep;16(9):799-811. doi: 10.1002/term.3327. Epub 2022 Jun 11.
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.
在住院的 COVID-19 患者中,有 20%-25%发生急性心脏损伤。在此,我们证明人类心脏类器官(hCO)是模拟 COVID-19 过度炎症引起的心脏损伤的可行平台。由于白细胞介素-1β(IL-1β)是一种上游细胞因子和 COVID-19 的核心特征性细胞因子,因此我们用其刺激 hCO 以诱导释放出一组促炎细胞因子,这些细胞因子反映了 COVID-19 细胞因子风暴的特征。经 IL-1β 处理的 hCO 再现了 COVID-19 心脏的转录组、结构和功能特征。与 COVID-19 尸检的心脏组织相比,经 IL-1β 处理的 hCO 说明了过度炎症在 COVID-19 心脏损伤中的关键作用,并表明内皮具有心脏保护作用。因此,经 IL-1β 处理的 hCO 为评估免疫调节剂药物的疗效和潜在副作用,以及在基线和模拟运动条件下 COVID-19 心脏损伤的可逆性提供了一个明确而强大的模型。