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.; Lindner, Diana; Westermann, Dirk; Mei, Ying

doi:10.1101/2022.01.31.478497

Cited by 4 publications

(3 citation statements)

References 80 publications

(115 reference statements)

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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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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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“…Moreover, the vascularity of IL-1β-treated organoids exhibited prothrombotic features, including the upregulated expressions of ICAM1, E-selectin, and VAP1. On the other hand, NOS3 expression was downregulated, leading to impaired nitric oxide-mediated endothelial functions [ 127 ].…”

Section: Ipsc-derived Organoids In Covid-19 Modelingmentioning

confidence: 99%

Induced Pluripotent Stem Cell-Derived Organoids: Their Implication in COVID-19 Modeling

Csöbönyeiová

Klein

Kuniaková

et al. 2023

IJMS

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The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a significant global health issue. This novel virus’s high morbidity and mortality rates have prompted the scientific community to quickly find the best COVID-19 model to investigate all pathological processes underlining its activity and, more importantly, search for optimal drug therapy with minimal toxicity risk. The gold standard in disease modeling involves animal and monolayer culture models; however, these models do not fully reflect the response to human tissues affected by the virus. However, more physiological 3D in vitro culture models, such as spheroids and organoids derived from induced pluripotent stem cells (iPSCs), could serve as promising alternatives. Different iPSC-derived organoids, such as lung, cardiac, brain, intestinal, kidney, liver, nasal, retinal, skin, and pancreatic organoids, have already shown immense potential in COVID-19 modeling. In the present comprehensive review article, we summarize the current knowledge on COVID-19 modeling and drug screening using selected iPSC-derived 3D culture models, including lung, brain, intestinal, cardiac, blood vessels, liver, kidney, and inner ear organoids. Undoubtedly, according to reviewed studies, organoids are the state-of-the-art approach to COVID-19 modeling.

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“…However, as organoids are made largely from epithelial cells of tissues, macrophages and vasculatures are usually missing 14 . Because macrophages are a major mediator of cytokine release syndrome and damage vasculature, the lack of these effectors and targets hampers key knowledge from organoid models [15][16][17] . Having vascular networks and immune cells in organoids is a promising venue 18 .…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids

Chau,

To,

Au-Yeung

et al. 2024

Preprint

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SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.

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

Cited by 4 publications

References 80 publications

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

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

Induced Pluripotent Stem Cell-Derived Organoids: Their Implication in COVID-19 Modeling

SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids

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