Comparison of 10 Control hPSC Lines for Drug Screening in an Engineered Heart Tissue Format
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Comparison of 10 Control hPSC Lines for Drug Screening in an Engineered Heart Tissue Format. / Mannhardt, Ingra; Saleem, Umber; Mosqueira, Diogo; Loos, Malte F; Ulmer, Bärbel M; Lemoine, Marc D; Larsson, Camilla; Améen, Caroline; de Korte, Tessa; Vlaming, Maria L H; Harris, Kate; Clements, Peter; Denning, Chris; Hansen, Arne; Eschenhagen, Thomas.
In: STEM CELL REP, Vol. 15, No. 4, 13.10.2020, p. 983-998.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Comparison of 10 Control hPSC Lines for Drug Screening in an Engineered Heart Tissue Format
AU - Mannhardt, Ingra
AU - Saleem, Umber
AU - Mosqueira, Diogo
AU - Loos, Malte F
AU - Ulmer, Bärbel M
AU - Lemoine, Marc D
AU - Larsson, Camilla
AU - Améen, Caroline
AU - de Korte, Tessa
AU - Vlaming, Maria L H
AU - Harris, Kate
AU - Clements, Peter
AU - Denning, Chris
AU - Hansen, Arne
AU - Eschenhagen, Thomas
N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2020/10/13
Y1 - 2020/10/13
N2 - 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.
AB - 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.
U2 - 10.1016/j.stemcr.2020.09.002
DO - 10.1016/j.stemcr.2020.09.002
M3 - SCORING: Journal article
C2 - 33053362
VL - 15
SP - 983
EP - 998
JO - STEM CELL REP
JF - STEM CELL REP
SN - 2213-6711
IS - 4
ER -