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Related Experiment Video

Updated: Jan 8, 2026

Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation
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Advantages of long-term evaluation of doxorubicin-induced cardiotoxicity using human iPSC-derived cardiomyocyte sheet

Yuto Hinata1,2, Yuki Kagawa1, Takanori Seno1

  • 1Ogino Memorial Laboratory, Nihon Kohden Corporation, TWIns, Tokyo 162-8666, Japan.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|December 19, 2025
PubMed
Summary

This study developed a new in vitro system to measure long-term cardiotoxicity from anticancer drugs. The system detected doxorubicin-induced heart cell damage earlier than traditional biomarkers.

Keywords:
cardiac contractilitycell sheet technologydoxorubicin-induced cardiotoxicityhuman-induced pluripotent stem cell-derived cardiomyocytes

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Area of Science:

  • Cardiovascular Research
  • Drug Discovery and Development
  • Stem Cell Biology

Background:

  • Delayed cardiotoxicity from anticancer therapies is a growing concern.
  • Precise in vitro models are needed for evaluating long-term cardiotoxic effects.
  • Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer a promising model system.

Purpose of the Study:

  • To evaluate the long-term cardiotoxic effects of doxorubicin using a novel in vitro system.
  • To assess the contractility of hiPSC-CM cell sheet tissues under continuous measurement.
  • To compare the sensitivity of contractile force measurement versus soluble biomarkers for cardiotoxicity detection.

Main Methods:

  • hiPSC-CMs were cultured into cell sheet tissues and paced at a steady 1 Hz.
  • Continuous contractile force was measured over 5 days in tissues exposed to 0.3 µM doxorubicin.
  • Post-measurement biomarkers (ANP, BNP, NT-proBNP, cTnT) were analyzed.

Main Results:

  • Doxorubicin exposure led to progressive force decline and arrhythmias.
  • No significant changes were observed in the analyzed soluble biomarkers.
  • An increased relaxation slope preceded contraction amplitude reduction, with early phase force decline being prominent.

Conclusions:

  • Indirect biomarker assessment may be insufficient for detecting doxorubicin cardiotoxicity.
  • The rate-controlled, continuous force platform provides a more sensitive in vitro method for preclinical cardiotoxicity screening.
  • This system reveals early cardiotoxicity changes missed by soluble biomarkers, aiding drug development.