Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model for Drug Cardiotoxicity Screening

Abstract

Background: Cardiomyocytes derived from human induced pluripotent stem cells offer a human cardiac substrate for safety
pharmacology, and have been adopted faster than they have been validated.
Objective: To review what these cells have been shown to predict, the assay platforms used, and the limitations that qualify
the result.
Methods: Narrative review of differentiation and maturation studies, assay development, and the blinded multisite
validation work.
Findings: A ten-site blinded study of 28 drugs separated low-risk from higher-risk compounds with an area under the curve
of 0.872, and a consortium study reported 81% sensitivity and 87% specificity. Against this, the cell line contributed more
variance than the testing site, and monolayer cells carry roughly half the sodium current density of adult myocardium.
Conclusions: The cells detect repolarisation delay reliably. Specificity, not sensitivity, is the unresolved problem, and the
regulatory framework treats them as confirmatory rather than primary