Senior Vice President Axion Biosystems Atlanta, Georgia, United States
Abstract: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC) are now established as a widely used model system in the safety pharmacology and disease modelling communities. The International Society for Stem Cell Research (ISSCR) recently released ‘Standards for Human Stem Cell Use in Research’, a document that outlines a set of recommendations that establish the minimum characterization and reporting criteria for working with human stem cells. The overarching goal of these criteria is to standardize practices, and in doing so, improve the quality of results. However, there are still no agreed-upon minimum acceptance criteria for the functional activity of hiPSC cardiomyocyte models. Rather, it is left to the end-user to determine whether the electrophysiological phenotype of their cell model is fit for purpose.
Over the last decade, the multielectrode array (MEA) field potential assay has become a popular tool for characterizing the electrical activity of hiPSC-cardiomyocyte batches, studying cardiac disease models, screening for new therapeutics, and evaluating drug-induced cardiotoxicity. The goal of this project is to set the minimum acceptance criteria for a spontaneous beating wild type hiPSC-ventricular cardiomyocyte field potential assay for compound testing and/or disease modeling.
Using our own experience with hiPSC-cardiomyocytes in our respective labs in academia and in industry, our work with international consortia developing hiPSC-cardiomyocyte assays (CiPA and JiCSA), combined with published data, we have developed a proposed standard focused on the hiPSC-cardiomyocyte spontaneous beat rate, features of the cardiac waveform (depolarization spike amplitude and field potential duration), and the synchronization of activity in the syncytia. Cell performance data from leading commercial sources of hiPSC-cardiomyocytes with respect to this proposed standard will also be presented for reference.
Funding Source: National Institutes of Health (NIH) Grant R01HD108839 (NGP) and F31HL165818 (DG). American Heart Association Grant 23PRE1021149 (DG)
