Using human cardiomyocytes for safety pharmacology studies
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great potential for safety pharmacology studies. Human iPSC-derived cardiomyocytes can be used in different platforms, such as patch-clamp, MEA and impedance, and for different applications, such as high-throughput screening and disease modeling.
A collaborative study presented at the SPS meeting in Berlin
The PhysioStim team recently presented a comparative study between human cardiomyocytes and isolated guinea-pig ventricular cardiomyocytes at the last Safety Pharmacology Society meeting in Berlin. The study is a collaborative project between PhysioStim and Ncardia (formerly Pluriomics) and was designed to compare the effects of reference compounds in both Pluricyte® Cardiomyocytes and the well-established model of freshly isolated guinea-pig ventricular cardiomyocytes, which are currently recommended in the ICH S7B guideline.
Human cardiomyocytes and CIPA
Besides providing interesting new study opportunities, human cardiomyocytes are a major focus of the Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative to screen the proarrhythmic potential of drug candidates. The CiPA initiative aims to set new standards for the assessment of proarrhythmic risk, using new technologies and a better understanding of torsadogenic mechanisms, which will no longer be limited to hERG assays. However, before they can be truly adopted, human iPSC-derived models require thorough characterization.
Promising first results
The comparative study showed that action potential measurements in Pluricyte® Cardiomyocytes using the patch-clamp technique have a relevant ventricular electrophysiology profile. The effects of various compounds, ranging from specific to multiple ion channel modulators, were correctly identified. Pluricyte® Cardiomyocytes also seem to be more sensitive than freshly isolated guinea-pig cardiomyocytes when it comes to detecting the torsadogenic potential of compounds. These first results are highly promising and may well confirm that human cardiomyocytes could be a major asset for future safety pharmacology studies. However, to further validate the sensitivity and specificity of hiPSC cardiomyocytes, a broader selection of compounds with proarrhythmic potential is required.
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