Engineered Human Cardiac Microtissues: The State-of-the-(He)art

Soon, Kayla; Mourad, Omar; Nunes, Sara S.

doi:10.1002/stem.3376

Cited by 9 publications

(11 citation statements)

References 65 publications

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“…[18][19][20] We would like to direct readers to who wish to gain more familiarity with principles of HOC, designs and fabrication approaches or who would like more details to published reviews that cover these particular aspects. 11,15,17,21 Different heart diseases can be modeled using HOC platforms through diverse approaches, such as modification of cell composition, 22 addition of soluble factors, 18,23 or using cells from specific genetic backgrounds [24][25][26][27] (Figure 3). As mentioned previously, HOC disease models offer distinct advantages over monolayer and animal models, with a comparison of different approaches summarized in the Table 1.…”

Section: Cardiovascular Organoids/ 3d Models Review Seriesmentioning

confidence: 99%

“…8,9 To address the limitations of traditional cardiac disease models, 2 different yet overlapping tissue engineering approaches have been employed in the generation of cardiac microtissues: spheroid/organoid or hearton-a-chip (HOC) tissues. [10][11][12] Spheroid or organoidstyle cardiac tissue engineering approaches rely on the self-assembly of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and other cell types into spherical structures. 13,14 These spheroids offer advantages over traditional monolayer approaches such as displaying a more native architecture and enabling improved cell-cell communication between CMs and other cell types while using fewer cells than other tissue engineering approaches.…”

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confidence: 99%

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Modeling Heart Diseases on a Chip: Advantages and Future Opportunities

Mourad

Yee

et al. 2023

Circulation Research

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Heart disease is a significant burden on global health care systems and is a leading cause of death each year. To improve our understanding of heart disease, high quality disease models are needed. These will facilitate the discovery and development of new treatments for heart disease. Traditionally, researchers have relied on 2D monolayer systems or animal models of heart disease to elucidate pathophysiology and drug responses. Heart-on-a-chip (HOC) technology is an emerging field where cardiomyocytes among other cell types in the heart can be used to generate functional, beating cardiac microtissues that recapitulate many features of the human heart. HOC models are showing great promise as disease modeling platforms and are poised to serve as important tools in the drug development pipeline. By leveraging advances in human pluripotent stem cell-derived cardiomyocyte biology and microfabrication technology, diseased HOCs are highly tuneable and can be generated via different approaches such as: using cells with defined genetic backgrounds (patient-derived cells), adding small molecules, modifying the cells’ environment, altering cell ratio/composition of microtissues, among others. HOCs have been used to faithfully model aspects of arrhythmia, fibrosis, infection, cardiomyopathies, and ischemia, to name a few. In this review, we highlight recent advances in disease modeling using HOC systems, describing instances where these models outperformed other models in terms of reproducing disease phenotypes and/or led to drug development.

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Section: Cardiovascular Organoids/ 3d Models Review Seriesmentioning

confidence: 99%

mentioning

confidence: 99%

Modeling Heart Diseases on a Chip: Advantages and Future Opportunities

Mourad

Yee

et al. 2023

Circulation Research

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“…Importantly, this tissue showed the ability to pump fluid, which resembled cardiac physiology, more specifically the Frank-Starling mechanism which describes the relationship between stroke volume and end-diastolic volume in the heart. 87,88 Collectively, engineered cardiac microtissues display a great opportunity in the field of cardiac regenerative/replacement approaches. However, for clinical applications, the transplantation strategies need to be improved in several ways.…”

Section: Engineered Cardiac Microtissuementioning

confidence: 99%

“…To model the native ventricle, hiPSC‐derived ventricular CMs were engineered into a human ventricle‐like cardiac organoid chamber. Importantly, this tissue showed the ability to pump fluid, which resembled cardiac physiology, more specifically the Frank–Starling mechanism which describes the relationship between stroke volume and end‐diastolic volume in the heart 87,88 …”

Section: Engineered Cardiac Microtissuementioning

confidence: 99%

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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“…At present, a variety of “cardiac tissue chips” have been developed to simulate and manipulate dynamic mechanical microenvironment of cardiac tissue at the micro-scale by combining with microfabrication or microfluidic technology, providing real-time insights into fibrosis events. Moreover, cardiac tissue chips can offer an extraordinary way to precisely manage different microenvironment signals (e.g., abnormal stretch or fluid shear stress) to construct biomimetic 3D in vitro cardiac fibrosis models ( Duval et al, 2017 ; Soon et al, 2021 ). For example, Zhao et al (2019) described a scalable tissue-cultivation platform that is cell source agnostic and enables drug testing under electrical pacing ( Figure 3C ).…”

Section: Dynamic Biomechanical Traitsmentioning

confidence: 99%

Dynamic and static biomechanical traits of cardiac fibrosis

Liu

Fan²,

Jin³

et al. 2022

Front. Bioeng. Biotechnol.

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Cardiac fibrosis is a common pathology in cardiovascular diseases which are reported as the leading cause of death globally. In recent decades, accumulating evidence has shown that the biomechanical traits of fibrosis play important roles in cardiac fibrosis initiation, progression and treatment. In this review, we summarize the four main distinct biomechanical traits (i.e., stretch, fluid shear stress, ECM microarchitecture, and ECM stiffness) and categorize them into two different types (i.e., static and dynamic), mainly consulting the unique characteristic of the heart. Moreover, we also provide a comprehensive overview of the effect of different biomechanical traits on cardiac fibrosis, their transduction mechanisms, and in-vitro engineered models targeting biomechanical traits that will aid the identification and prediction of mechano-based therapeutic targets to ameliorate cardiac fibrosis.

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Engineered Human Cardiac Microtissues: The State-of-the-(He)art

Cited by 9 publications

References 65 publications

Modeling Heart Diseases on a Chip: Advantages and Future Opportunities

Modeling Heart Diseases on a Chip: Advantages and Future Opportunities

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

Dynamic and static biomechanical traits of cardiac fibrosis

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