Cardiac differentiation of pluripotent stem cells and implications for modeling the heart in health and disease

Devalla, Harsha D.; Passier, Robert

doi:10.1126/scitranslmed.aah5457

Cited by 60 publications

(60 citation statements)

References 129 publications

(135 reference statements)

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“…In human cardiac research, the development of 3D cardiac organoids has proven a challenge due to the complex cellular environment and the diverse cell populations in the human heart, requiring a deeper biological understanding in order to create an optimum cardiac organoid platform . Cardiomyocyte differentiation is regulated by transcriptional pathways, which yield a diverse set of cardiomyocyte populations, such as sinoatrial nodal cells, atrioventricular cells, atrial cells, ventricular cells, and purkinje cells . Each of the populations is associated with specific cardiac diseases, which could be modeled through the use of organoids.…”

Section: Cell Sources For the Composition Of 3d Organoidsmentioning

confidence: 99%

“…In the context of the human heart, fibroblasts are responsible for myocardial tissue structure maintenance and remodeling through the synthesis of extracellular matrix, and they contribute directly to the electrical properties of the myocardium by physically insulating the atria from the ventricles . Endothelial cells have the function to regulate the contractile state of cardiomyocytes through autocrine and paracrine signaling molecules, and they are vital transporters of oxygen and nutrients as well as important modulators of vasomotor tone . Therefore, cardiomyocytes, cardiac fibroblasts, and cardiac endothelial cells should be tricultured to compose functional human cardiac organoids.…”

Section: Cell Sources For the Composition Of 3d Organoidsmentioning

confidence: 99%

“…The diverse subpopulations of cardiomyocytes that can be derived from hiPSCs to compose organoids allow for the in vitro modeling of a multitude of associated diseases: (i) sinoatrial nodal cells are relevant for modeling bradycardia‐tachycardia syndrome; (ii) atrioventricular nodal cells are suitable for atrioventricular block and atrioventricular nodal reentrant tachycardia; (iii) atrial cells are used for atrial fibrillation; (iv) ventricular cells are used for cardiomyopathies (hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy); and (v) purkinje cells are for congenital histiocytoid cardiomyopathy . Approaches of how to drive hiPSCs into specific subpopulations of cardiomyocytes are described by Devalla and Passier …”

Section: Cardiac Organoids Modeling Human Cardiac Diseases In Vitromentioning

confidence: 99%

“…19 Cardiomyocyte differentiation is regulated by transcriptional pathways, which yield a diverse set of cardiomyocyte populations, such as sinoatrial nodal cells, atrioventricular cells, atrial cells, ventricular cells, and purkinje cells. 20 Each of the populations is associated with specific cardiac diseases, which could be modeled through the use of organoids.…”

Section: Cell Sources For the Composition Of 3d Organoidsmentioning

confidence: 99%

“…23 Endothelial cells have the function to regulate the contractile state of cardiomyocytes through autocrine and paracrine signaling molecules, 24 and they are vital transporters of oxygen and nutrients as well as important modulators of vasomotor tone. 20 Therefore, cardiomyocytes, cardiac fibroblasts, and cardiac endothelial cells should be tricultured to compose functional human cardiac organoids.…”

Section: Cell Sources For the Composition Of 3d Organoidsmentioning

confidence: 99%

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Human Cardiac Organoids for Disease Modeling

Nugraha

Buono

Boehmer

et al. 2018

Clin Pharma and Therapeutics

116

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Human cardiac drug discovery and disease modeling face challenges in recapitulating cellular complexity and animal‐to‐human translation due to the limitations of conventional 2D cell culture and animal models. The development of human cardiac organoid technologies could help in stimulating and maintaining differentiated cell functions for extended periods of time. By closely mimicking in vivo organ functions in vitro they could thereby help in overcoming the obstacles mentioned above. Through the construction of human cardiac organoids from pluripotent stem cell–derived cells, derived from patients with specific known genotypes and phenotypes, more complex and robust in vitro tools have recently become available for disease modeling. In this review, we will describe the relevance and importance of evolving organoid platforms in disease biology. We further provide examples of cardiac organoid platforms, which may lead the way toward future personalized medicine and drug discovery.

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Section: Cell Sources For the Composition Of 3d Organoidsmentioning

confidence: 99%

Section: Cell Sources For the Composition Of 3d Organoidsmentioning

confidence: 99%

Section: Cardiac Organoids Modeling Human Cardiac Diseases In Vitromentioning

confidence: 99%

Section: Cell Sources For the Composition Of 3d Organoidsmentioning

confidence: 99%

Section: Cell Sources For the Composition Of 3d Organoidsmentioning

confidence: 99%

See 3 more Smart Citations

Human Cardiac Organoids for Disease Modeling

Nugraha

Buono

Boehmer

et al. 2018

Clin Pharma and Therapeutics

116

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Stem Cell Therapy of Myocardial Infarction: A Promising Opportunity in Bioengineering

Jiang

Shamul

et al. 2020

Advanced Therapeutics

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Myocardial infarction (MI) is a life‐threatening disease resulting from the irreversible death of cardiomyocytes (CMs). Stem cell‐based therapies have been studied for MI treatment over the last two decades with promising outcomes. Here, the past work in this field is critically reviewed to elucidate the advantages and disadvantages of treating MI using pluripotent stem cells (PSCs) including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), adult stem cells, and cardiac progenitor cells. Overall, PSCs (particularly iPSCs) have more advantages than the other cells for cardiac regeneration. However, the use of iPSCs is also facing critical challenges, which may be resolved by using biomaterials to engineer stem cells for reduced immunogenicity, improved immobilization/survival in the heart, and increased integration with the host cardiac tissue to eliminate arrhythmia. Biomaterials have also been applied in the derivation of CMs in vitro to increase the efficiency and maturation of cardiac differentiation. Collectively, a lot has been learned from the past failures of simply injecting intact stem cells or their derivatives in vivo for treating MI, and bioengineering stem cells with biomaterials may be a valuable strategy for advancing stem cell therapy towards its widespread application for MI treatment in the clinic.

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Accelerating cardiovascular research: recent advances in translational 2D and 3D heart models

Mohr

Thum

Bär

2022

European J of Heart Fail

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In vitro modelling the complex (patho‐) physiological conditions of the heart is a major challenge in cardiovascular research. In recent years, methods based on three‐dimensional (3D) cultivation approaches have steadily evolved to overcome the major limitations of conventional adherent two‐dimensional (2D) monolayer cultivation. These 3D approaches aim to study, reproduce or modify fundamental native features of the heart such as tissue organization and cardiovascular microenvironment. Therefore, these systems have great potential for (patient‐specific) disease research, for the development of new drug screening platforms, and for the use in regenerative and replacement therapy applications. Consequently, continuous improvement and adaptation is required with respect to fundamental limitations such as cardiomyocyte maturation, scalability, heterogeneity, vascularization, and reproduction of native properties. In this review, 2D monolayer culturing and the 3D in vitro systems of cardiac spheroids, organoids, engineered cardiac microtissue and bioprinting as well as the ex vivo technique of myocardial slicing are introduced with their basic concepts, advantages, and limitations. Furthermore, recent advances of various new approaches aiming to extend as well as to optimize these in vitro and ex vivo systems are presented.

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Cardiac differentiation of pluripotent stem cells and implications for modeling the heart in health and disease

Cited by 60 publications

References 129 publications

Human Cardiac Organoids for Disease Modeling

Human Cardiac Organoids for Disease Modeling

Stem Cell Therapy of Myocardial Infarction: A Promising Opportunity in Bioengineering

Accelerating cardiovascular research: recent advances in translational 2D and 3D heart models

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