Human cardiac organoids to model COVID-19 cytokine storm induced cardiac injuries

IF 3.1 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Tissue Engineering and Regenerative Medicine Pub Date : 2022-06-11 DOI:10.1002/term.3327

Dimitrios C. Arhontoulis, Charles M. Kerr, Dylan Richards, Kelsey Tjen, Nathaniel Hyams, Jefferey A. Jones, Kristine Deleon-Pennell, Donald Menick, Hanna Br?uninger, Diana Lindner, Dirk Westermann, Ying Mei

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引用次数: 12

Abstract

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.

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人类心脏类器官模拟COVID-19细胞因子风暴引起的心脏损伤

20%-25%的住院COVID-19患者发生急性心脏损伤。在此，我们证明了人类心脏类器官(hCOs)是一个可行的平台来模拟COVID-19高炎症引起的心脏损伤。由于IL-1β是一种上游细胞因子，也是COVID-19的核心特征细胞因子，因此研究人员使用IL-1β刺激hCOs诱导释放一系列促炎细胞因子，这些促炎细胞因子反映了COVID-19细胞因子风暴的特征。IL-1β处理的hCOs重现了COVID-19心脏的转录组学、结构和功能特征。IL-1β处理的hCOs与COVID-19尸检心脏组织的比较表明，高炎症在COVID-19心脏损伤中的关键作用，并提示内皮细胞的心脏保护作用。因此，IL-1β治疗的hCOs提供了一个明确且稳健的模型，用于评估免疫调节药物的疗效和潜在副作用，以及基线和模拟运动条件下COVID-19心脏损伤的可逆性。

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来源期刊

Journal of Tissue Engineering and Regenerative Medicine 生物-工程：生物医学

CiteScore

7.50

自引率

3.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Journal of Tissue Engineering and Regenerative Medicine publishes rapidly and rigorously peer-reviewed research papers, reviews, clinical case reports, perspectives, and short communications on topics relevant to the development of therapeutic approaches which combine stem or progenitor cells, biomaterials and scaffolds, growth factors and other bioactive agents, and their respective constructs. All papers should deal with research that has a direct or potential impact on the development of novel clinical approaches for the regeneration or repair of tissues and organs. The journal is multidisciplinary, covering the combination of the principles of life sciences and engineering in efforts to advance medicine and clinical strategies. The journal focuses on the use of cells, materials, and biochemical/mechanical factors in the development of biological functional substitutes that restore, maintain, or improve tissue or organ function. The journal publishes research on any tissue or organ and covers all key aspects of the field, including the development of new biomaterials and processing of scaffolds; the use of different types of cells (mainly stem and progenitor cells) and their culture in specific bioreactors; studies in relevant animal models; and clinical trials in human patients performed under strict regulatory and ethical frameworks. Manuscripts describing the use of advanced methods for the characterization of engineered tissues are also of special interest to the journal readership.