Heart slice culture system reliably demonstrates clinical drug-related cardiotoxicity

Miller, Jessica M.; Meki, Moustafa; Ou, Qinghui; George, Sharon A.; Gams, Anna; Abouleisa, Riham; Tang, Xian‐Liang; Ahern, Brooke M.; Giridharan, Guruprasad A.; El-Baz, Ayman; Hill, Bradford G.; Satin, Jonathan; Conklin, Daniel J.; Moslehi, Javid; Bolli, Roberto; Ribeiro, Alexandre J. S.; Efimov, Igor R.; Mohamed, Tamer

doi:10.1016/j.taap.2020.115213

Cited by 25 publications

(25 citation statements)

References 64 publications

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“…Thin heart slices are a relatively new technology that has emerged in recent years and has shown promise in providing a system of adequate complexity and viability to allow for drug screening ( Miller et al, 2020 ). They retain the adult phenotype, including the adult heart’s multicellularity and extracellular structure, and have been produced from human cardiac tissue and large mammals.…”

Section: In-vitro Modeling Of the Human Myocardiummentioning

confidence: 99%

“…Current preclinical cardiotoxicity systems are failing to detect the cardiotoxicity of many drugs ( Gwathmey et al, 2009 ). We have recently shown that our optimized heart slice system ( Ou et al, 2019 ) can reliably detect drug-related cardiotoxicity ( Miller et al, 2020 ). Three medications from three different anticancer categories were tested (doxorubicin, trastuzumab, and sunitinib).…”

Section: Applications Of Heart Slices As a Cardiotoxicity Screening Pmentioning

confidence: 99%

“…First, the exact nutrients needed to further maintain the metabolic activities and mitochondrial utilization rates in the presence of several nutrients such as fatty acids, glucose, fructose, corticosteroids, and hormones of heart slices. Our lab has performed the only study to provide a proof of concept study to show that heart slices can reflect clinical phenotypes of cardiotoxins ( Miller et al, 2020 ). This study used three known cardiotoxins at three different concentrations and assessed effects at one time point (48 h).…”

Section: Current Limitations and Future Perspective Of The Cardiac Slmentioning

confidence: 99%

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Heart Slices to Model Cardiac Physiology

2021

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Translational research in the cardiovascular field is hampered by the unavailability of cardiac models that can recapitulate organ-level physiology of the myocardium. Outside the body, cardiac tissue undergoes rapid dedifferentiation and maladaptation in culture. There is an ever-growing demand for preclinical platforms that allow for accurate, standardized, long-term, and rapid drug testing. Heart slices is an emerging technology that solves many of the problems with conventional myocardial culture systems. Heart slices are thin (<400 µm) slices of heart tissue from the adult ventricle. Several recent studies using heart slices have shown their ability to maintain the adult phenotype for prolonged periods in a multi cell-type environment. Here, we review the current status of cardiac culture systems and highlight the unique advantages offered by heart slices in the light of recent efforts in developing physiologically relevant heart slice culture systems.

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Section: In-vitro Modeling Of the Human Myocardiummentioning

confidence: 99%

Section: Applications Of Heart Slices As a Cardiotoxicity Screening Pmentioning

confidence: 99%

Section: Current Limitations and Future Perspective Of The Cardiac Slmentioning

confidence: 99%

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Heart Slices to Model Cardiac Physiology

2021

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“…Ultimately, the ideal experimental cardiac tissue culture model is the one that demonstrates high sensitivity and specificity towards various therapeutic and pharmacological interventions while accurately replicating the physiology and pathophysiology of the human heart ( Wang et al, 2008 ). The recent move towards the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) ( Burridge et al, 2016 ) and human heart slices ( Ou et al, 2019 ; Miller et al, 2020 ; Ou et al, 2020 ) in cardiotoxicity testing provided a potential solution to address this issue. In this special issue we have 12 manuscripts, seven review articles and five original research articles summarizing the recent advances in cardiotoxicity testing.…”

Section: Introductionmentioning

confidence: 99%

“…hiPSC-CM systems are ideal for high-throughput testing and for proof-of-principle evaluations of patient-specific genetic backgrounds or disease mutations; however, the incomplete maturation and lack of multicellularity creates caveats. The use of slice preparations is an exciting advance in test platforms because this native tissue preparation retains phenotypic properties in vitro ( Ou et al, 2019 ; Miller et al, 2020 ; Ou et al, 2020 ). Finally, Meki et al reviewed the use of adult human and pig heart slices in cardiotoxicity testing.…”

Section: Introductionmentioning

confidence: 99%

Editorial: Recent Advances in Cardiotoxicity Testing

2021

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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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Heart slice culture system reliably demonstrates clinical drug-related cardiotoxicity

Cited by 25 publications

References 64 publications

Heart Slices to Model Cardiac Physiology

Heart Slices to Model Cardiac Physiology

Editorial: Recent Advances in Cardiotoxicity Testing

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

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