SarcTrack

Toepfer, Christopher N.; Sharma, Arun; Cicconet, Marcelo; Garfinkel, Amanda C; Mücke, Michael; Neyazi, Meraj; Willcox, Jon A. L.; Agarwal, Radhika; Schmid, Manuel; Rao, Jyoti; Ewoldt, Jourdan; Pourquié, Olivier; Chopra, Anant; Chen, Christopher; Seidman, Jonathan G.; Seidman, Christine E.

doi:10.1161/circresaha.118.314505

Cited by 105 publications

(63 citation statements)

References 34 publications

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“…HiPSC-CMs express ACE2, which increases over 90 days of differentiation (Churko et al, 2018). The hiPSC-CMs are also responsive to inotropic drugs such as norepinephrine, and beating rates can be controlled via electrical stimulation (Toepfer et al, 2019). Because hiPSC-CMs can be purified and replated for downstream applications, research groups in academia and industry now utilize these cells for cardiovascular disease modeling and high-throughput drug screening assays.…”

Section: Introductionmentioning

confidence: 99%

Human iPSC-Derived Cardiomyocytes are Susceptible to SARS-CoV-2 Infection

Sharma

García

Arumugaswami

et al. 2020

Preprint

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115

152

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words):Coronavirus disease 2019 is a viral pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is predominantly defined by respiratory symptoms, but cardiac complications including arrhythmias, heart failure, and viral myocarditis are also prevalent. Although the systemic ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well-understood. We used human induced pluripotent stem cellderived cardiomyocytes (hiPSC-CMs) as a model system to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and immunofluorescence demonstrated that SARS-CoV-2 can enter and replicate within hiPSC-CMs, localizing at perinuclear locations within the cytoplasm. Viral cytopathic effect induced hiPSC-CM apoptosis and cessation of beating after 72 hours of infection. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating the mechanisms of infection and potentially a cardiac-specific antiviral drug screening platform.was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

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Section: Introductionmentioning

confidence: 99%

Human iPSC-Derived Cardiomyocytes are Susceptible to SARS-CoV-2 Infection

Sharma

García

Arumugaswami

et al. 2020

Preprint

Self Cite

115

152

View full text Add to dashboard Cite

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“… c) Structural readouts of sarcomere dynamics reported using the SarcTrack analysis software developed by Toepfer et al [ 119 ] …”

Section: Assays Used In Cardiotoxicity Studies To Measure Active Forcementioning

confidence: 99%

“…“SarcTrack” is one such video analysis tool that tracks the displacement of fluorescently labeled sarcomeric proteins to reveal changes to sarcomere length and shortening. [ 119 ] Not surprisingly, sarcomere length changes have been correlated with contractile force. [ 120 ] Toepfer et al used of SarcTrack to detect changes to sarcomere function in response to drug treatment using a small molecule that alters myosin function.…”

Section: Assays Used In Cardiotoxicity Studies To Measure Active Forcementioning

confidence: 99%

“…[ 120 ] Toepfer et al used of SarcTrack to detect changes to sarcomere function in response to drug treatment using a small molecule that alters myosin function. [ 119 ] Monitoring such changes at the level of sarcomere structure and function will enable new insights into mechanisms of action of cardiotoxic compounds. With continued improvements in imaging tools and analysis software, video microscopy analysis will continue to be a cornerstone of drug discovery and screening assays.…”

Section: Assays Used In Cardiotoxicity Studies To Measure Active Forcementioning

confidence: 99%

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Mechanobiology Assays with Applications in Cardiomyocyte Biology and Cardiotoxicity

Blair

Pruitt

2020

Adv Healthcare Materials

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Cardiomyocytes are the motor units that drive the contraction and relaxation of the heart. Traditionally, testing of drugs for cardiotoxic effects has relied on primary cardiomyocytes from animal models and focused on short‐term, electrophysiological, and arrhythmogenic effects. However, primary cardiomyocytes present challenges arising from their limited viability in culture, and tissue from animal models suffers from a mismatch in their physiology to that of human heart muscle. Human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) can address these challenges. They also offer the potential to study not only electrophysiological effects but also changes in cardiomyocyte contractile and mechanical function in response to cardiotoxic drugs. With growing recognition of the long‐term cardiotoxic effects of some drugs on subcellular structure and function, there is increasing interest in using hiPSC‐CMs for in vitro cardiotoxicity studies. This review provides a brief overview of techniques that can be used to quantify changes in the active force that cardiomyocytes generate and variations in their inherent stiffness in response to cardiotoxic drugs. It concludes by discussing the application of these tools in understanding how cardiotoxic drugs directly impact the mechanobiology of cardiomyocytes and how cardiomyocytes sense and respond to mechanical load at the cellular level.

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“…Because disease models have shown changes in contraction force, modulators of contractility are under investigation. The allosteric modulator of cardiac myosin, mavacamten, reduces contractility by decreasing the ATPase activity of cardiac MHC in a mouse model of HCM [101], also showing effectiveness in reversing the hypercontactility seen in truncated MYBPC hPSC-CM mutants [108]. Phase III clinical trials are now ongoing to test mavacamten efficacy in adults with symptomatic obstructive HCM (ClinicalTrials.gov NCT03470545), with completion expected in June 2020 [97].…”

Section: Trends In Molecular Medicinementioning

confidence: 99%