2022 - Tackling Chronic Compound Responses of hiPSC-CMs for Preclinical Cardiac Risk Evaluation: Defined Serum-Free Medium and Long-Term Culture on the FLEXcyte 96
FLEXcyte 96 poster, BPS 2022 
(1.03 MB)
Abstract:
In pre-clinical drug development, cardiac contraction analysis of potential drug candidates is one of the crucial steps to ensure a successful and reliable transition to clinical stages. The use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) continues to increase in the assessment of safety and toxicological side effects of newly developed compounds, due to their reproducibility and low ethical concern. However, the obstacles of an immature phenotype as well as the need of serum-containing media for chronic assays raise concerns over non-physiological responses in preclinical drug development. To solve this issue, a variety of methods are currently being tested to foster hiPSC-CM maturation in vitro and to conduct chronic studies without the need of serum containing medium. Here we assessed the effects of relatively defined medium (serum-free) and prolonged cell culture times on iCell® Cardiomyocytes² maturation with focus on functional contractile properties using the FLEXcyte 96 technology. Analysis of iCell Cardiomyocytes² contractile properties cultured in iCell Cardiomyocytes Serum-free Medium compared to being cultured in regular serum-containing iCell Cardiomyocytes Maintenance Medium showed similar results for most parameters and expected effects of gold standard compounds assessed over 5 days. In addition, iCell Cardiomyocytes², cultured on FLEXcyte 96 plates and analyzed for 40 days, showed an increase in amplitude and a decrease in beat rate over time, indicating the pro-maturation effect of a physiological environment over time
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