Advanced Cardiovascular Toxicity Screening: Integrating Human iPSC-Derived Cardiomyocytes with 2D In Silico Models.

IF 3.4 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Toxicology Pub Date : 2025-03-28 DOI:10.1007/s12012-025-09987-1

Anastasiya Sinitsyna, Andrey Berezhnoy, Ivan Semidetnov, Vadim Naumov, Tatyana Sergeeva, Sergey Bakumenko, Mikhail Slotvitsky, Valeriya Tsvelaya, Konstantin Agladze

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引用次数: 0

Abstract

The pharmaceutical industry is evolving with the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) for in vitro cardiac safety screening. Traditional reliance on QT-interval prolongation as a main arrhythmogenicity marker is being challenged. In addition, the Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative recommends using computer modeling and in silico platforms as a more comprehensive approach for arrhythmogenicity testing in conjunction with hiPSC-CM in vitro screening. Our study presents an innovative platform that integrates in vitro hiPSC-CM propagation test with in silico models to assess the potential arrhythmogenic effect of drug-induced impact on ionic currents and electrophysiological intercellular coupling. Utilizing the electrophysiological and morphological characteristics of hiPSC-CM, we offer a thorough evaluation of potential drug-induced cardiac risks by computer modeling. We show, using the examples of lidocaine (100-300 μM) and Cyclophosphamide (639, 852 μM), that with the use of an integrative experimental and computer platform, it is possible to correctly display the clinical manifestations of side effects in advance.

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来源期刊

Cardiovascular Toxicology 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

>12 weeks

期刊介绍： Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.