Development of a drug screening system using three-dimensional cardiac tissues containing multiple cell types

Takeda, Maki; Miyagawa, Shigeru; Ito, Emiko; Harada, Akira; Mochizuki-Oda, Noriko; Matsusaki, Michiya; Akashi, Mitsuru; Sawa, Yoshiki

doi:10.1038/s41598-021-85261-y

Cited by 12 publications

(9 citation statements)

References 36 publications

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“…Thanks to its scalability, this technique can be used for drug screening on the one hand and cardiac repair on the other hand. In [ 144 ], hiPSC-CMs and cardiac fibroblasts were coated with ECM proteins and mixed in different ratios with endothelial cells. With an appropriate hiPSC-CMs:CFs:ECs ratio, a modification of the contractile properties could be seen in the presence of E-4031 and isoproterenol.…”

Section: Different Geometries For Different Readouts and Applicationsmentioning

confidence: 99%

Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

et al. 2021

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Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.

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Section: Different Geometries For Different Readouts and Applicationsmentioning

confidence: 99%

Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

et al. 2021

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“…This platform has the additional benefit of microgrooves providing anisotropic cell patterning that more closely represents native myocardium. Other groups have developed methods of coating hPSC-CMs and other cell types with ECM and seeding them into cell sheets that are multiple layers thick [ 44 , 45 ]. Using motion tracking, it was possible to measure the effects of several drug compounds on magnitude of contraction, contraction kinetics, and abnormal beat intervals [ 44 ].…”

Section: Engineered Cardiac Platforms For Drug Screeningmentioning

confidence: 99%

A Change of Heart: Human Cardiac Tissue Engineering as a Platform for Drug Development

et al. 2022

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Purpose of Review Human cardiac tissue engineering holds great promise for early detection of drug-related cardiac toxicity and arrhythmogenicity during drug discovery and development. We describe shortcomings of the current drug development pathway, recent advances in the development of cardiac tissue constructs as drug testing platforms, and the challenges remaining in their widespread adoption. Recent Findings Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been used to develop a variety of constructs including cardiac spheroids, microtissues, strips, rings, and chambers. Several ambitious studies have used these constructs to test a significant number of drugs, and while most have shown proper negative inotropic and arrhythmogenic responses, few have been able to demonstrate positive inotropy, indicative of relative hPSC-CM immaturity. Summary Several engineered human cardiac tissue platforms have demonstrated native cardiac physiology and proper drug responses. Future studies addressing hPSC-CM immaturity and inclusion of patient-specific cell lines will further advance the utility of such models for in vitro drug development.

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“…CMs are the leading cardiac cell component (70–80% of myocardial volume) responsible for heart function and contraction by coupling cytoplasmatic Ca 2+ increase with force generation ( Notbohm et al, 2019 ). CMs are connected between each other and with other different cardiac cell types, modulating the maturation of CMs as demonstrated by co-culture in vitro studies ( Talman and Kivelä, 2018 ; Giacomelli et al, 2020 ; Tsukamoto et al, 2020 ; Campostrini et al, 2021 ; Takeda et al, 2021 ). The advantages of the primary CMs use are associated with the sarcomeric structure ideal for patch-clamp/contractility studies, the presence of ion channels ideal for Ca 2+ imaging studies, a large number of available genetic models, and the responsiveness to hypertrophic stimuli ( Peter et al, 2016 ).…”

Section: Cell Types For In Vitro Studiesmentioning

confidence: 99%

Cardiac tissue engineering: Multiple approaches and potential applications

Gisone

Cecchettini

Ceccherini

et al. 2022

Front. Bioeng. Biotechnol.

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The overall increase in cardiovascular diseases and, specifically, the ever-rising exposure to cardiotoxic compounds has greatly increased in vivo animal testing; however, mainly due to ethical concerns related to experimental animal models, there is a strong interest in new in vitro models focused on the human heart. In recent years, human pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) emerged as reference cell systems for cardiac studies due to their biological similarity to primary CMs, the flexibility in cell culture protocols, and the capability to be amplified several times. Furthermore, the ability to be genetically reprogrammed makes patient-derived hiPSCs, a source for studies on personalized medicine. In this mini-review, the different models used for in vitro cardiac studies will be described, and their pros and cons analyzed to help researchers choose the best fitting model for their studies. Particular attention will be paid to hiPSC-CMs and three-dimensional (3D) systems since they can mimic the cytoarchitecture of the human heart, reproducing its morphological, biochemical, and mechanical features. The advantages of 3D in vitro heart models compared to traditional 2D cell cultures will be discussed, and the differences between scaffold-free and scaffold-based systems will also be spotlighted.

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Development of a drug screening system using three-dimensional cardiac tissues containing multiple cell types

Cited by 12 publications

References 36 publications

Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

A Change of Heart: Human Cardiac Tissue Engineering as a Platform for Drug Development

Cardiac tissue engineering: Multiple approaches and potential applications

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