ReviewInduced pluripotent stem cell-derived cardiomyocytes: A platform for testing for drug cardiotoxicity

- Off-target cardiotoxicity is found in up to 30% of new drugs and is a major limitation to drug development.
- Current methods for assessment of drug cardiotoxicity have unacceptably high false positive and false negative rates.
- hiPSC-CMs represent an exciting new platform for testing for drug efficacy and cardiotoxicity.
- hiPSC-CMs have the capacity to replicate the genetic diversity present in human drug responses.
- hiPSC-CMs open a new window in pharmacogenomics and personalized medicine

Off-target cardiotoxicity has been a significant impediment to the development of new drugs. Traditional platforms for screening for cardiotoxicity are both overly sensitive and limited in their ability to predict cardiotoxicity that is often only uncovered after years of clinical use. A major impediment has been the lack of a human cardiomyocyte cell line. The recent discovery that adult somatic human cells (white blood cells or skin fibroblasts) can be reprogrammed into pluripotent stem cells (hiPSCs) and then differentiated into beating cardiomyocytes (hiPSC-CMs) provides an exciting new platform for drug cardiotoxicity and efficacy testing. One major advantage of using patient-derived hiPSC-CMs for drug testing is their ability to recapitulate population genetic variations (single nucleotide polymorphisms) that influence drug toxicity, providing a powerful new tool in the field of pharmacogenomics and personalized medicine.