The FDA’s Comprehensive in vitro Proarrythmia Assay (CiPA) initiative aims to provide a thorough preclinical cardiac safety profile of new chemical entities that enables prediction of human clinical proarrhythmia risk. To allow the successful utilisation of commercial human iPSC-derived cardiomyocytes (iPSC-CM) as models of human CM in the CiPA safety paradigm, their biophysical and pharmacological profile needs to be fully characterised. Here we will highlight our work to assess the utility of Axiogenesis vCor.4U iPSC-CM for CiPA-relevant cardiotoxicity screening.
Optical voltage imaging of human iPSC-derived cardiomyocytes was used to assess electrophysiological effects of compounds beyond hERG inhibition. Action potential waveform analysis revealed compound-specific and concentration-dependent changes, enabling mechanistic differentiation of multichannel activity and demonstrating a human-relevant approach for translational cardiac safety assessment.
The presence of sensory neuron markers, excitability properties consistent with sensory neurons, and evidence of nociceptor ion channels (using both RNASeq and electrophysiology) provides strong evidence that iCell Sensory Neurons have a robust sensory neuron phenotype suitable for supporting pain discovery programs.