Cardiotoxicity & Drug Screening

Vivian Cao

Is Your Current Technology Predictive?

xCELLigence® Cardio and CardioECR instruments provide the answers:

  • Superb Predictivity: Easily screen and quickly identify short-term and long-term cardiac toxicity early in drug development. (Figure 1)
  • Easy and Flexible Work Flow: Simply plate the cells, start acquiring data, and perform combination treatments and chronic dosing.
  • Powerful Multiplexing: Simultaneous readout of cardiomyocyte contractility, integrated ion channel activity (Figure 2), and viability.
  • Full Control of Beating Rate Enables Functional Maturation: Directed pacing feature improves functionality of iPSC cardiomyocytes (Figure 3) and response to inotropic compounds.
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Figure 1. Pharmacological assessment of ion channel inhibitors using iCell cardiomyocytes. iCell cardiomyocytes exhibiting consistent and robust beating activity (14 days post-seeding) were treated with multiple concentrations of each compound for up to 24 hours. Compound-induced arrhythmia was recorded by the xCELLigence RTCA Cardio instrument. 

 

Figure 2. Cardiac excitation-contraction coupling. The xCELLigence CardioECR instrument simultaneously measures electrophysiological signals and contractility. Blebbistatin, a myosin inhibitor, does not inhibit the ion-channel signal of treated cells (green), but greatly impairs the mechanical contraction and beating (red). Being able to monitor this excitation-contraction coupling relationship provides a complete picture for safety assessment of compounds during drug development.

 

Figure 3. Beating amplitude and Beating Rate Relations over time. iCell cardiomyocytes exhibiting consistent and robust beating and field potential signals were either submitted to directed progressive electrical stimulation (Paced) using the xCELLigence CardioECR instrument or cultured without electrical stimulation (Spontaneous) for 3 weeks. The Beating amplitude and Beating Rate relationship was determined weekly.

Download the Functional Maturation of iPSC Cardiomyocytes Flyer

Examples of xCELLigence RTCA Cardio and CardioECR Applications:

  1. Toxicity Screening
  2. Drug Discovery
  3. Genetic Diseases of the Heart

 

 

Cardiotoxicity & Drug Screening Supporting Information:

  • Compatible xCELLigence® Systems
xCELLigence RTCA Cardio xCELLigence RTCA CardioECR
RTCA Cardio RTCA CardioECR
Throughput 1×96 wells 1×48 wells
Readout Impedance only Impedance and Field Potential
Sampling Rate Impedance: 12.9 ms Impedance: 1 ms
Field Potential: 10 kHz
  • Cardiotoxicity Publications:
  1. Estimating the Risk of Drug-induced Proarrhythmia Using Human Induced Pluripotent Stem Cell-derived Cardiomyocytes. Guo L, Abrams RM, Babiarz JE, Cohen JD, Kameoka S, Sanders MJ, Chiao E, Kolaja KL. Toxicol Sci. 2011 Sep;123(1):281-9. (Hoffmann-La Roche, Nutley, USA)
  2. Impedance-based Detection of Beating Rhythm and Proarrhythmic Effects of Compounds on Stem Cell-derived Cardiomyocytes. Jonsson MK, Wang QD, Becker B. Assay Drug Dev Technol. 2011 Dec;9(6):589-99. (Roche R&D, Sweden)
  3. Functional Cardiotoxicity Profiling and Screening Using the xCELLigence RTCA Cardio System. Xi B, Wang T, Li N, Ouyang W, Zhang W, Wu J, Xu X, Wang X, Abassi YA. J Lab Autom. 2011 Dec;16(6):415-21. (ACEA Biosciences, Inc., USA)
  4. In vitro Model for Assessing Arrhythmogenic Properties of Drugs Based on high-resolution Impedance Measurements. Nguemo F, Šarić T, Pfannkuche K, Watzele M, Reppel M, Hescheler J. Cell Physiol Biochem. 2012;29(5-6):819-32. (University of Cologne, Germany)
  5. Dynamic Monitoring of Beating Periodicity of Stem Cell-derived Cardiomyocytes as a Predictive Tool for Preclinical Safety Assessment. Abassi YA, Xi B, Li N, Ouyang W, Seiler A, Watzele M, Kettenhofen R, Bohlen H, Ehlich A, Kolossov E, Wang X, Xu X. Br J Pharmacol. 2012 Mar;165(5):1424-41. (ACEA Biosciences, Inc.,USA)
  6. Drug-induced Functional Cardiotoxicity Screening in Stem Cell-derived Human and Mouse Cardiomyocytes: Effects of Reference Compounds. Himmel HM. J Pharmacol Toxicol Methods. 2013 Jul-Aug;68(1):97-111. (Bayer Pharma AG, Germany)
  7. Refining the Human iPSC Cardiomyocyte Arrhythmic Risk Assessment Model. Guo L, Coyle L, Abrams RM, Kemper R, Chiao ET, Kolaja KL. Toxicol Sci. 2013 Dec;136(2):581-94. (Hoffmann-La Roche, Inc., Nutley, USA)
  8. The Proliferative and Chronotropic Effects of Brillantaisia Nitens Lindau (Acanthaceae) Extracts on Pluripotent Stem Cells and Their Cardiomyocytes Derivatives. Nembo EN, Dimo T, Bopda OS, Hescheler J, Nguemo F. J Ethnopharmacol. 2014 Oct 28;156:73-81. (University of Cologne, Germany)
  9. Chapter 16: Label-Free Impedance Measurements for Profiling Drug- Induced Cardiotoxicity. Nguemo F, Semmler J, Hescheler J. Label-Free Biosensor Methods in Drug Discovery 2015 (University of Cologne, Germany)