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Effects of Serum and Compound Preparation Methods on Delayed Repolarization Evaluation With Human iPSC-CMs.
- Source :
-
Toxicological Sciences . Jul2022, Vol. 188 Issue 1, p48-61. 14p. - Publication Year :
- 2022
-
Abstract
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used in the Comprehensive in vitro Proarrhythmia Assay (CiPA). The notable difference of the electrophysiological (EP) responses of hiPSC-CMs in serum and serum-free media (SFM) is puzzling and may impact regulatory decision-making on the cardiac safety of candidate drugs in inducing QT prolongation and torsade de pointes (TdP). In this study, we compared the EP responses of hiPSC-CMs to 10 CiPA compounds and moxifloxacin in serum and SFM; explained the potential reason behind the different EP responses—abiotic compound loss to plastic tubes/plates of hydrophobic compounds prepared in SFM; and investigated the impact of compound preparation methods on drug bioavailability in exposure media, which affects the TdP risk prediction of drugs tested in serum-containing and SFM. For assays to be conducted in SFM, awareness of abiotic compound loss of hydrophobic compounds in serum-free preparations is critical for delay repolarization evaluation and data extrapolation from in vitro to in vivo. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10966080
- Volume :
- 188
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Toxicological Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 157681794
- Full Text :
- https://doi.org/10.1093/toxsci/kfac043