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Unlocking Personalized Biomedicine and Drug Discovery with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Fit for Purpose or Forever Elusive?
- Source :
- Annual review of pharmacology and toxicology. 60
- Publication Year :
- 2019
-
Abstract
- 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decades, drug development costs have increased by approximately a hundredfold, and yet about 1 in 7 licensed drugs are withdrawn from the market, often due to cardiotoxicity.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.
- Subjects :
- 0301 basic medicine
Computer science
Induced Pluripotent Stem Cells
Toxicology
Organ-on-a-chip
Genome engineering
03 medical and health sciences
0302 clinical medicine
Drug Development
Drug Discovery
CRISPR
Animals
Humans
Myocytes, Cardiac
Precision Medicine
Induced pluripotent stem cell
Biomedicine
Pharmacology
business.industry
Drug discovery
Cas9
Cardiotoxicity
030104 developmental biology
Drug development
Risk analysis (engineering)
CRISPR-Cas Systems
business
Genetic Engineering
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15454304
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Annual review of pharmacology and toxicology
- Accession number :
- edsair.doi.dedup.....54095ed443b6f607bb6d7f1db3349bdb