Unlocking Personalized Biomedicine and Drug Discovery with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Fit for Purpose or Forever Elusive?
Standard
Unlocking Personalized Biomedicine and Drug Discovery with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Fit for Purpose or Forever Elusive? / de Korte, Tessa; Katili, Puspita A; Mohd Yusof, Nurul A N; van Meer, Berend J; Saleem, Umber; Burton, Francis L; Smith, Godfrey L; Clements, Peter; Mummery, Christine L; Eschenhagen, Thomas; Hansen, Arne; Denning, Chris.
in: ANNU REV PHARMACOL, Jahrgang 60, 06.01.2020, S. 529-551.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Unlocking Personalized Biomedicine and Drug Discovery with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Fit for Purpose or Forever Elusive?
AU - de Korte, Tessa
AU - Katili, Puspita A
AU - Mohd Yusof, Nurul A N
AU - van Meer, Berend J
AU - Saleem, Umber
AU - Burton, Francis L
AU - Smith, Godfrey L
AU - Clements, Peter
AU - Mummery, Christine L
AU - Eschenhagen, Thomas
AU - Hansen, Arne
AU - Denning, Chris
PY - 2020/1/6
Y1 - 2020/1/6
N2 - In recent decades, drug development costs have increased by approximately a hundredfold, and yet about 1 in 7 licensed drugs are withdrawn from the market, often due to cardiotoxicity. This review considers whether technologies using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could complement existing assays to improve discovery and safety while reducing socioeconomic costs and assisting with regulatory guidelines on cardiac safety assessments. We draw on lessons from our own work to suggest a panel of 12 drugs that will be useful in testing the suitability of hiPSC-CM platforms to evaluate contractility. We review issues, including maturity versus complexity, consistency, quality, and cost, while considering a potential need to incorporate auxiliary approaches to compensate for limitations in hiPSC-CM technology. We give examples on how coupling hiPSC-CM technologies with Cas9/CRISPR genome engineering is starting to be used to personalize diagnosis, stratify risk, provide mechanistic insights, and identify new pathogenic variants for cardiovascular disease.
AB - In recent decades, drug development costs have increased by approximately a hundredfold, and yet about 1 in 7 licensed drugs are withdrawn from the market, often due to cardiotoxicity. This review considers whether technologies using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could complement existing assays to improve discovery and safety while reducing socioeconomic costs and assisting with regulatory guidelines on cardiac safety assessments. We draw on lessons from our own work to suggest a panel of 12 drugs that will be useful in testing the suitability of hiPSC-CM platforms to evaluate contractility. We review issues, including maturity versus complexity, consistency, quality, and cost, while considering a potential need to incorporate auxiliary approaches to compensate for limitations in hiPSC-CM technology. We give examples on how coupling hiPSC-CM technologies with Cas9/CRISPR genome engineering is starting to be used to personalize diagnosis, stratify risk, provide mechanistic insights, and identify new pathogenic variants for cardiovascular disease.
U2 - 10.1146/annurev-pharmtox-010919-023309
DO - 10.1146/annurev-pharmtox-010919-023309
M3 - SCORING: Review article
C2 - 31506008
VL - 60
SP - 529
EP - 551
JO - ANNU REV PHARMACOL
JF - ANNU REV PHARMACOL
SN - 0362-1642
ER -