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 Y.; Menick, Donald R.; Bräuninger, Hanna; Lindner, Diana; Westermann, Dirk; Mei, Ying

doi:10.1002/term.3327

Cited by 17 publications

(5 citation statements)

References 81 publications

(97 reference statements)

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“…Follow-up studies showed that this model was transcriptomically similar to adult myocardium ( Kerr et al, 2021 ) and that its vascularization could be increased by the upregulation of the hypoxia-inducible factor HIF-α ( Coyle et al, 2021 ). Furthermore, these microtissues were used to model cardiac injuries caused by COVID-19 hyperinflammation through stimulation with IL-1β to mimic a cytokine storm ( Arhontoulis et al, 2022 ).…”

Section: Cardiac Microtissuesmentioning

confidence: 99%

Heart in a dish – choosing the rightin vitromodel

Drakhlis

Zweigerdt

2023

Disease Models &Amp; Mechanisms

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The heart is the first functional organ established during embryogenesis. Investigating heart development and disease is a fascinating and crucial field of research because cardiovascular diseases remain the leading cause of morbidity and mortality worldwide. Therefore, there is great interest in establishing in vitro models for recapitulating both physiological and pathological aspects of human heart development, tissue function and malfunction. Derived from pluripotent stem cells, a large variety of three-dimensional cardiac in vitro models have been introduced in recent years. In this At a Glance article, we discuss the available methods to generate such models, grouped according to the following classification: cardiac organoids, cardiac microtissues and engineered cardiac tissues. For these models, we provide a systematic overview of their applications for disease modeling and therapeutic development, as well as their advantages and limitations to assist scientists in choosing the most suitable model for their research purpose.

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Section: Cardiac Microtissuesmentioning

confidence: 99%

Heart in a dish – choosing the rightin vitromodel

Drakhlis

Zweigerdt

2023

Disease Models &Amp; Mechanisms

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“…Organoids, due to their ability to closely mimic the cellular composition and internal architecture of native organs and their ability to be derived from patient-specific cells, offer the promise to overcome the major limitations in using animal and 2D cell culture models as mentioned above to investigate viral infection in human. Using respective organoid models, studies have demonstrated that COVID-19 affects not only the lung 43,44 but also the heart, 45,46 gastrointestinal tract, 47 blood vessels, and kidney. 48 These echo the multi-organ dysfunction observed in human patients infected by severe acute respiratory syndrome coronavirus 2.…”

Section: Challenges and Future Directionsmentioning

confidence: 99%

Alliance of Heart and Endoderm: Multilineage Organoids to Model Co-development

Varghese

Jia

et al. 2023

Circulation Research

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Studies in animal models tracing organogenesis of the mesoderm-derived heart have emphasized the importance of signals coming from adjacent endodermal tissues in coordinating proper cardiac morphogenesis. Although in vitro models such as cardiac organoids have shown great potential to recapitulate the physiology of the human heart, they are unable to capture the complex crosstalk that takes place between the co-developing heart and endodermal organs, partly due to their distinct germ layer origins. In an effort to address this long-sought challenge, recent reports of multilineage organoids comprising both cardiac and endodermal derivatives have energized the efforts to understand how inter-organ, cross-lineage communications influence their respective morphogenesis. These co-differentiation systems have produced intriguing findings of shared signaling requirements for inducing cardiac specification together with primitive foregut, pulmonary, or intestinal lineages. Overall, these multilineage cardiac organoids offer an unprecedented window into human development that can reveal how the endoderm and heart cooperate to direct morphogenesis, patterning, and maturation. Further, through spatiotemporal reorganization, the co-emerged multilineage cells self-assemble into distinct compartments as seen in the cardiac-foregut, cardiac-intestine, and cardiopulmonary organoids and undergo cell migration and tissue reorganization to establish tissue boundaries. Looking into the future, these cardiac incorporated, multilineage organoids will inspire future strategies for improved cell sourcing for regenerative interventions and provide more effective models for disease investigation and drug testing. In this review, we will introduce the developmental context of coordinated heart and endoderm morphogenesis, discuss strategies for in vitro co-induction of cardiac and endodermal derivatives, and finally comment on the challenges and exciting new research directions enabled by this breakthrough.

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“…111,112 Human cardiac organoids and vascular organoids have been established to explore SARS-CoV-2 infectivity in the cardiovascular system. 42,113,114 Mils et al demonstrated that infected cardiac organoids could recapitulate key clinical features of diastolic malfunction in COVID-19 patients. 115 The study also showed that cytokine-induced cardiac dysfunction in cardiac organoids could be attenuated by using bromodomain and extraterminal family inhibitors (BETi).…”

Section: Other Organoidsmentioning

confidence: 99%

“…SARS‐CoV‐2 infection can cause cardiac injury and dysfunction in patients and increase the risk of mortality 111,112 . Human cardiac organoids and vascular organoids have been established to explore SARS‐CoV‐2 infectivity in the cardiovascular system 42,113,114 . Mils et al demonstrated that infected cardiac organoids could recapitulate key clinical features of diastolic malfunction in COVID‐19 patients 115 .…”

Section: Human Organoids For Studying Sars‐cov‐2 Infectivitymentioning

confidence: 99%

Development trends of human organoid‐based COVID‐19 research based on bibliometric analysis

Yuan

Zou

et al. 2023

Cell Proliferation

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Coronavirus disease 2019 (COVID‐19), a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has posed a catastrophic threat to human health worldwide. Human stem cell‐derived organoids serve as a promising platform for exploring SARS‐CoV‐2 infection. Several review articles have summarized the application of human organoids in COVID‐19, but the research status and development trend of this field have seldom been systematically and comprehensively studied. In this review, we use bibliometric analysis method to identify the characteristics of organoid‐based COVID‐19 research. First, an annual trend of publications and citations, the most contributing countries or regions and organizations, co‐citation analysis of references and sources and research hotspots are determined. Next, systematical summaries of organoid applications in investigating the pathology of SARS‐CoV‐2 infection, vaccine development and drug discovery, are provided. Lastly, the current challenges and future considerations of this field are discussed. The present study will provide an objective angle to identify the current trend and give novel insights for directing the future development of human organoid applications in SARS‐CoV‐2 infection.

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

Cited by 17 publications

References 81 publications

Heart in a dish – choosing the rightin vitromodel

Heart in a dish – choosing the rightin vitromodel

Alliance of Heart and Endoderm: Multilineage Organoids to Model Co-development

Development trends of human organoid‐based COVID‐19 research based on bibliometric analysis

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