xCELLigence RTCA EPACER

As cell analysis in basic research, translational medicine, and cell therapies becomes ever more sophisticated, it is imperative that solutions provide multiparametric and data-rich information. In this application note, Agilent Technologies introduces its xCELLigence RTCA eSight for real-time cell analysis, featuring non-invasive impedance-based monitoring together with live-cell imaging, all inside your incubator. One experiment provides two simultaneous methods with 5 different readouts. Cellular impedance first provides sensitive and rapid information about cell viability, growth, morphology, and barrier function. Brightfield and three fluorescent channels monitor and quantify viability, toxicity, and apoptosis- validating cellular impedance readouts and further boosting confidence in your results. This combination of information enables for much wider sampling and the assessment of cellular processes and biology – all within a single experiment.

Pathogenic variants in MYH7 and MYBPC3 account for the majority of hypertrophic cardiomyopathy (HCM). However, targeted drugs like myosin ATPase inhibitors have not been evaluated in children.

Caroline Kinnear from Dr. Seema Mital’s group at the Hospital for Sick Children, Toronto, will describe how the team generated patient and variant-corrected iPSC-cardiomyocytes (CMs) from pediatric HCM patients harboring single variants in MYH7 (V606M; R453C) and MYBPC3 (G148R) or digenic variants (MYBPC3 P955fs, TNNI3 A157V). Compared with isogenic and healthy controls, variant-positive CMs showed hypertrophy, sarcomere disorganization, higher contractility, calcium transients, and ATPase activity.

Kinnear will also highlight how targeted myosin ATPase inhibitors showed complete rescue of the phenotype in variant-positive CMs and in cardiac biowires to mirror isogenic controls. The response was superior to verapamil or metoprolol. The findings indicate myosin inhibitors can be effective in genotypically diverse HCM highlighting the need for myosin inhibitor drug trials in pediatric HCM.

Key learning objectives

• Learn how a “disease-in-a-dish” approach can potentially improve the treatment of disease
• Gain insights into genotype-phenotype association using patient-derived iPSCs
• Explore how analytical tools, such as the xCELLigence RTCA CardioECR instrument, are used to elucidate the mechanisms of diseases and evaluate the effects of pharmacological and genetic interventions
• Understand the translational importance of targeted myosin inhibitor therapies for future clinical trials

Who should attend?

• Researchers and scientists in industry and academia, basic and translational cardio disease researchers, and cardio drug discovery enthusiasts.

Certificate of attendance
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