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Updated: Jul 28, 2025

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers
Published on: March 24, 2023
Large-scale microRNA functional high-throughput screening identifies miR-515-3p and miR-519e-3p as inducers of human
Harsha V Renikunta1,2,3, Katina Lazarow4, Yiqi Gong5
1Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care, Hindenburgdamm 30, 12203 Berlin, Germany.
Abstract:
Ischemic cardiomyopathy, driven by loss of cardiomyocytes and inadequate proliferative response, persists to be a major global health problem. Using a functional high-throughput screening, we assessed differential proliferative potential of 2019 miRNAs after transient hypoxia by transfecting both miR-inhibitor and miR-mimic libraries in human iPSC-CM. Whereas miR-inhibitors failed to enhance EdU uptake, overexpression of 28 miRNAs substantially induced proliferative activity in hiPSC-CM, with an overrepresentation of miRNAs belonging to the primate-specific C19MC-cluster. Two of these miRNAs, miR-515-3p and miR-519e-3p, increased markers of early and late mitosis, indicative of cell division, and substantially alter signaling pathways relevant for cardiomyocyte proliferation in hiPSC-CM.

