Cardiotoxicity evaluation using human embryonic stem cells and induced pluripotent stem cell-derived cardiomyocytes

Zhao, Qi; Wang, Xijie; Wang, Shuyan; Song, Zheng; Wang, Jiaxian; Ma, Jing

doi:10.1186/s13287-017-0473-x

Cited by 28 publications

(15 citation statements)

References 22 publications

(18 reference statements)

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“…Cardiotoxicity is still one of the primary factors restricting the development of drugs. Drug development is a time-consuming and expensive process, and past statistics show that up to 90% of compounds that passed pre-clinical screening were terminated in a clinical trial, with approximately 45% of those failures being due to cardiotoxicity [1]. In addition, many drugs that were originally on the market have been withdrawn due to clinical cases of cardiotoxicity.…”

Section: Introductionmentioning

confidence: 99%

An integrated characterization of contractile, electrophysiological, and structural cardiotoxicity of Sophora tonkinensis Gapnep. in human pluripotent stem cell-derived cardiomyocytes

Wang

et al. 2019

Stem Cell Res Ther

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BackgroundCardiotoxicity remains an important concern in drug discovery and clinical medication. Meanwhile, Sophora tonkinensis Gapnep. (S. tonkinensis) held great value in the clinical application of traditional Chinese medicine, but cardiotoxic effects were reported, with matrine, oxymatrine, cytisine, and sophocarpine being the primary toxic components.MethodsIn this study, impedance and extracellular field potential (EFP) of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were recorded using the cardio non-labeled cell function analysis and culture system (Cardio-NLCS). The effects of matrine, oxymatrine, cytisine, and sophocarpine (2, 10, 50 μM) on cell viability; level of lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), and cardiac troponin I (CTn-I); antioxidant activities; production of reactive oxygen species (ROS) and malondialdehyde (MDA); and disruption of intracellular calcium homeostasis were also added into the integrated assessment.ResultsThe results showed that matrine and sophocarpine dose-dependently affected both impedance and EFP, while oxymatrine and cytisine altered impedance significantly. Our study also indicated that cardiotoxicity of matrine, oxymatrine, cytisine, and sophocarpine was related to the disruption of calcium homeostasis and oxidative stress. Four alkaloids of S. tonkinensis showed significant cardiotoxicity with dose dependence and structural cardiotoxicity synchronized with functional changes of cardiomyocytes.ConclusionsThis finding may provide guidance for clinical meditation management. Furthermore, this study introduced an efficient and reliable approach, which offers alternative options for evaluating the cardiotoxicity of the listed drugs and novel drug candidates.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1126-4) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

An integrated characterization of contractile, electrophysiological, and structural cardiotoxicity of Sophora tonkinensis Gapnep. in human pluripotent stem cell-derived cardiomyocytes

Wang

et al. 2019

Stem Cell Res Ther

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“…Due to the high incidence of drug-induced heart failure and irreversible arrhythmia, the pre-clinical evaluation of the cardiotoxicity of drugs is important ( 23 ). However, efficient approaches to evaluate the cardiotoxicity of traditional or novel treatments have been lacking.…”

Section: Discussionmentioning

confidence: 99%

Aconitine‑induced cardiac arrhythmia in human induced pluripotent stem cell‑derived cardiomyocytes

et al. 2018

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Pre-clinical evaluation of cardiac dysfunction is important for assessing the safety of traditional or novel medicines due to the universality of potential drug-induced heart failure and irreversible arrhythmia. Aconitine (ACO), a traditionally used anti-pyretic, analgesic and anti-rheumatic drug, has been reported to have arrhythmogenic effects. In the present study, the Real-Time Cellular Analysis Cardio system was applied to evaluate the arrhythmogenic effects of ACO in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The results indicated that ACO is capable of increasing the frequency and decreasing the amplitude of hiPSC-CM contraction in a dose- and time-dependent manner. ACO at 0.25 µM increased the beating rate of hiPSC-CMs by 3.7-fold within 30 min, while 3.0 µM of ACO increased the beating rate by 7.3-fold. The present study also evaluated the potential pro-apoptotic effects of ACO by using caspase-3 and caspase-9 kits. To the best of our knowledge, the present study was the first to record the ACO-induced cardiac arrhythmia of hiPSC-CMsin real-time. The results also indicate that ACO-induced cell death is mediated, at least in part, by caspase-dependent apoptotic pathways.

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“…Cardiac toxicity is one of the major factors affecting success in drug tests in clinical studies [1]. In total, 90% of drugs that enter clinical trials fail to commercialize owing to their toxic side effects on the heart [2]. Hence, development of such techniques that can measure electrophysiology and contraction force of cardiomyocytes is of critical importance.…”

Section: Introductionmentioning

confidence: 99%

Polymer-Based Functional Cantilevers Integrated with Interdigitated Electrode Arrays—A Novel Platform for Cardiac Sensing

2020

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Heart related ailments are some of the most common causes for death in the world, and some of the causes are cardiac toxicity due to drugs. Several platforms have been developed in this regard over the years that can measure electrical or mechanical behavior of cardiomyocytes. In this study, we have demonstrated a biomedical device that can simultaneously measure electrophysiology and contraction force of cardiomyocytes. This dual-function device is composed of a photosensitive polymer-based cantilever, with a pair of metal-based interdigitated electrodes on its surface, such that the cantilever can measure the contraction force of cardiomyocytes and the electrodes can measure the impedance between cells and substrate. The cantilever is patterned with microgrooves so that the cardiomyocytes can align to the cantilever in order to make a higher cantilever deflection in response to contraction force. Preliminary experimental results have identified the potential for use in the drug-induced cardiac toxicity tests, and further optimization is desirable to extend the technique to various bio-sensor areas.

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Cardiotoxicity evaluation using human embryonic stem cells and induced pluripotent stem cell-derived cardiomyocytes

Cited by 28 publications

References 22 publications

An integrated characterization of contractile, electrophysiological, and structural cardiotoxicity of Sophora tonkinensis Gapnep. in human pluripotent stem cell-derived cardiomyocytes

An integrated characterization of contractile, electrophysiological, and structural cardiotoxicity of Sophora tonkinensis Gapnep. in human pluripotent stem cell-derived cardiomyocytes

Aconitine‑induced cardiac arrhythmia in human induced pluripotent stem cell‑derived cardiomyocytes

Polymer-Based Functional Cantilevers Integrated with Interdigitated Electrode Arrays—A Novel Platform for Cardiac Sensing

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