• Our CiPA Instruments

    HESI FDA BAA study: "Assessing variability and reproducibility of manual and automated patch clamp platforms"

  • CiPA hERG Protocol

    This protocol was used for hERG studies on the Patchliner and SyncroPatch 384PE.

  • HTS CiPA hERG Assay

    Effects of Cisapride using the CiPA hERG protocol on the SyncroPatch 384PE

  • Myocyte & Ion Channel Effects

    Arrhythmic Field potentials in iPSC-derived Cardiomyocytes (CardioExcyte 96) and hERG current inhibition (SyncroPatch 384PE)

  • Gigaseal HTS patch clamp

    CiPA-specified cardiac ion channels recorded at high throughput

  • Gigaseal HTS patch clamp

    High throughput recordings of cardiac ion channels at physiological temperature

  • CardioExcyte 96 screening tool

    CardioExcyte 96 with integrated liquid handling for cardiac safety screening

2020 - Repolarization studies using human stem cell-derived cardiomyocytes: Validation studies and best practice recommendations

CiPA review in Regulatory Toxicology and Pharmacology (2020)

Authors:
Gintant G., Kaushik E.P., Feaster T., Stoelzle-Feix S., Kanda Y., Osada T., Smith G., Czysz K., Kettenhofen R., Rong Lu H., Cai B., Shi H., Herron T.J., Dang Q., Burton F., Pang L., Traebert M., Abassi Y., Beck Pierson J., Blinova K.

Journal:
Regulatory Toxicology and Pharmacology (2020) doi: 10.1016/j.yrtph.2020.104756


Abstract:

Human stem cell-derived cardiomyocytes (hSC-CMs) hold great promise as in vitro models to study the elec-trophysiological effects of novel drug candidates on human ventricular repolarization. Two recent large vali-dation studies have demonstrated the ability of hSC-CMs to detect drug-induced delayed repolarization and “cellrhythmias” (interrupted repolarization or irregular spontaneous beating of myocytes) linked to Torsade-de- Pointes proarrhythmic risk. These (and other) studies have also revealed variability of electrophysiological re-sponses attributable to differences in experimental approaches and experimenter, protocols, technology plat-forms used, and pharmacologic sensitivity of different human-derived models. Thus, when evaluating drug- induced repolarization effects, there is a need to consider 1) the advantages and disadvantages of different approaches, 2) the need for robust functional characterization of hSC-CM preparations to define “fit for purpose” applications, and 3) adopting standardized best practices to guide future studies with evolving hSC-CM prepa-rations. Examples provided and suggested best practices are instructional in defining consistent, reproducible, and interpretable “fit for purpose” hSC-CM-based applications. Implementation of best practices should enhance the clinical translation of hSC-CM-based cell and tissue preparations in drug safety evaluations and support their growing role in regulatory filings.


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