Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids

Silva, Ana C.; Matthys, Oriane B.; Joy, David A; Kauss, M. Ariel; Natarajan, Vaishaali; Lai, Michael H.; Turaga, Diwakar; Blair, Andrew; Alexanian, Michael; Bruneau, Benoit G.; McDevitt, Todd C.

doi:10.1016/j.stem.2021.11.007

Cited by 79 publications

(109 citation statements)

References 79 publications

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“…This is in line with protocols mentioned above that are able to generate endodermal cells [97,98]. Endocardial and epicardial cells could also spontaneously form and line the chamber cavity [100,101] or outer surface [98,101], respectively. The co-culture of epicardial cells with cardiac chamber organoids was also developed to bet-ter mimic the three-layer formation in in vivo heart tissue [100].…”

Section: Generation Of Cardiac Organoids From Hpscssupporting

confidence: 87%

“…While the heart consists of several distinct cell types, the Wnt modulation strategy is likely to generate endoderm-derived cell types as Wnt activation is also needed for endoderm specification [126]. This is in line with protocols mentioned above that are able to generate endodermal cells [97,98]. Endocardial and epicardial cells could also spontaneously form and line the chamber cavity [100,101] or outer surface [98,101], respectively.…”

Section: Generation Of Cardiac Organoids From Hpscsmentioning

confidence: 53%

“…Cardiomyocytes from these organoids reflect a SHF-like identity. Another approach applies similar Wnt modulation early and cultures the organoids in a medium that supports multiple lineages [98]. This process generates organoids with a cardiomyocyte core surrounded by endodermal and epicardial cells.…”

Section: Generation Of Cardiac Organoids From Hpscsmentioning

confidence: 99%

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Harnessing the Power of Stem Cell Models to Study Shared Genetic Variants in Congenital Heart Diseases and Neurodevelopmental Disorders

Chang

Tchieu

2022

Cells

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Advances in human pluripotent stem cell (hPSC) technology allow one to deconstruct the human body into specific disease-relevant cell types or create functional units representing various organs. hPSC-based models present a unique opportunity for the study of co-occurring disorders where “cause and effect” can be addressed. Poor neurodevelopmental outcomes have been reported in children with congenital heart diseases (CHD). Intuitively, abnormal cardiac function or surgical intervention may stunt the developing brain, leading to neurodevelopmental disorders (NDD). However, recent work has uncovered several genetic variants within genes associated with the development of both the heart and brain that could also explain this co-occurrence. Given the scalability of hPSCs, straightforward genetic modification, and established differentiation strategies, it is now possible to investigate both CHD and NDD as independent events. We will first overview the potential for shared genetics in both heart and brain development. We will then summarize methods to differentiate both cardiac & neural cells and organoids from hPSCs that represent the developmental process of the heart and forebrain. Finally, we will highlight strategies to rapidly screen several genetic variants together to uncover potential phenotypes and how therapeutic advances could be achieved by hPSC-based models.

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Section: Generation Of Cardiac Organoids From Hpscssupporting

confidence: 87%

Section: Generation Of Cardiac Organoids From Hpscsmentioning

confidence: 53%

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Harnessing the Power of Stem Cell Models to Study Shared Genetic Variants in Congenital Heart Diseases and Neurodevelopmental Disorders

Chang

Tchieu

2022

Cells

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“…Two recent studies with human iPSCs succeeded in the co-production of cardiac and gastrointestinal tissue in single organoids without organized chambers (Silva et al, 2021; Drakhlis et al, 2021). As well, Hofbauer et al (2021) succeeded in generating self-organized, isolated cardioids exhibiting chamber-like structures from human pluripotent stem cells that were used to model cardiac injury (Hofbauer et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

A Combined Human Gastruloid Model of Cardiogenesis and Neurogenesis

Olmsted

Paluh

2022

Preprint

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Multi-lineage development from gastruloids is enabling unprecedented opportunities to model and study human embryonic processes and is expected to accelerate ex vivo strategies in organ development. Reproducing human cardiogenesis with neurogenesis in a multi-lineage context remains challenging, requiring spatiotemporal input of paracrine and mechanical cues. Here we extend elongating multi-lineage organized (EMLO) gastruloids to include cardiogenesis (EMLOC) and describe interconnected neuro-cardiac lineages in a single gastruloid model. Contractile EMLOCs recapitulate numerous interlinked developmental features including heart tube formation and specialization, cardiomyocyte differentiation and remodeling phases, epicardium, ventricular wall morphogenesis, chamber-like structures and formation of a putative outflow tract. The EMLOC cardiac region, which originates anterior to gut tube primordium, is progressively populated by neurons in a spatial pattern mirroring the known distribution of neurons in the innervated human heart. This human EMLOC model represents the first multi-lineage advancement for the study of coincident neurogenesis and cardiogenesis.

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“…1 ). In a more recent example, a multilineage organoid protocol was introduced wherein there is a sequential emergence of cardiac mesoderm followed by gut endoderm over 100 days in culture [ 23 ]. The sequence of morphogenetic events reported in this organoid model is believed to recapitulate stages that occur after the ‘heart tube’ formation.…”

Section: Introductionmentioning

confidence: 99%

An evidence appraisal of heart organoids in a dish and commensurability to human heart development in vivo

Thomas

Perez

Sayed

2022

BMC Cardiovasc Disord

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Stem-cell derived in vitro cardiac models have provided profound insights into mechanisms in cardiac development and disease. Efficient differentiation of specific cardiac cell types from human pluripotent stem cells using a three-step Wnt signaling modulation has been one of the major discoveries that has enabled personalized cardiovascular disease modeling approaches. Generation of cardiac cell types follow key development stages during embryogenesis, they intuitively are excellent models to study cardiac tissue patterning in primitive cardiac structures. Here, we provide a brief overview of protocols that have laid the foundation for derivation of stem-cell derived three-dimensional cardiac models. Further this article highlights features and utility of the models to distinguish the advantages and trade-offs in modeling embryonic development and disease processes. Finally, we discuss the challenges in improving robustness in the current models and utilizing developmental principles to bring higher physiological relevance. In vitro human cardiac models are complimentary tools that allow mechanistic interrogation in a reductionist way. The unique advantage of utilizing patient specific stem cells and continued improvements in generating reliable organoid mimics of the heart will boost predictive power of these tools in basic and translational research.

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Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids

Cited by 79 publications

References 79 publications

Harnessing the Power of Stem Cell Models to Study Shared Genetic Variants in Congenital Heart Diseases and Neurodevelopmental Disorders

Harnessing the Power of Stem Cell Models to Study Shared Genetic Variants in Congenital Heart Diseases and Neurodevelopmental Disorders

A Combined Human Gastruloid Model of Cardiogenesis and Neurogenesis

An evidence appraisal of heart organoids in a dish and commensurability to human heart development in vivo

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