Summary Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are commercially available, and cardiac differentiation established routine. Systematic evaluation of several control hiPSC-CM is lacking. We investigated 10 different control hiPSC-CM lines and analyzed function and suitability for drug screening. Five commercial and 5 academic hPSC-CM lines were casted in engineered heart tissue (EHT) format. Spontaneous and stimulated EHT contractions were analyzed, and 7 inotropic indicator compounds investigated on 8 cell lines. Baseline contractile force, kinetics, and rate varied widely among the different lines (e.g., relaxation time range: 118-471 ms). In contrast, the qualitative correctness of responses to BayK-8644, nifedipine, EMD-57033, isoprenaline, and digoxin in terms of force and kinetics varied only between 80% and 93%. Large baseline differences between control cell lines support the request for isogenic controls in disease modeling. Variability appears less relevant for drug screening but needs to be considered, arguing for studies with more than one line.
Graphical Abstract
Highlights • EHTs are stable from all tested hPSC-CM control lines • EHT baseline contractility shows high levels of variability between cell lines • Batch-to-batch variability is a large confounder of contractile parameters • Despite baseline variability, canonical drug responses were seen in all lines
In this article, Mannhardt and colleagues show that a systematic evaluation of 10 control hPSC-CM lines (commercial and academic) revealed high levels of variability regarding baseline contractility between the lines. In contrast, inotropic drug effects showed less prominent variability in canonical responses, arguing for a smaller relevance in drug screening.