Functional Characterization of Human Stem Cell-Derived Cardiomyocytes

Glenn E Kirsch1, Carlos A Obejero-Paz1, Andrew Bruening-Wright1

  • 1ChanTest Corporation, Cleveland, Ohio USA.

Insights

Early cardiac toxicity testing using human stem cell-derived cardiomyocytes (SC-hCM) helps predict drug risks. This method uses SC-hCM electrophysiology to assess potential cardiac dangers, improving drug safety.

Area of Science:

  • Cardiovascular pharmacology
  • Stem cell biology
  • Drug safety assessment

Background:

  • Cardiac toxicity is a major cause of drug attrition and market withdrawal.
  • Accurate early-stage cardiac risk assessment is crucial for drug development.
  • Primary human cardiomyocytes are limited, necessitating alternative models.

Purpose of the Study:

  • To describe methods for assessing cardiac risk using human stem cell-derived cardiomyocytes (SC-hCM).
  • To highlight the utility of SC-hCM electrophysiology in early drug safety evaluation.
  • To provide techniques for recording key electrophysiological parameters.

Main Methods:

  • Recording of individual ion currents (sodium, calcium, potassium) in SC-hCM.
  • Measurement of single-cell action potentials.
  • Impedance recordings from contracting SC-hCM syncytia.

Main Results:

  • Established techniques for detailed electrophysiological analysis of SC-hCM.
  • Demonstrated the feasibility of assessing cardiac ion channel function and action potentials.
  • Enabled evaluation of cardiac network activity through impedance measurements.

Conclusions:

  • Human stem cell-derived cardiomyocytes (SC-hCM) provide a viable model for early cardiac safety testing.
  • SC-hCM electrophysiology is a valuable tool for predicting drug-induced cardiotoxicity.
  • These methods aid in mitigating cardiac risks during drug discovery and development.