Comparison of 10 Control hPSC Lines for Drug Screening in an Engineered Heart Tissue Format
Ingra Mannhardt, Umber Saleem, Diogo Mosqueira, Malte Loos, Bärbel Ulmer, Marc D. Lemoine, Camilla Larsson, Caroline Améen, Tessa de Korte, Maria L.H. Vlaming, Kate Harris, Peter Clements, Chris Denning, Arne Hansen, Thomas Eschenhagen
Abstract
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.