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A humanized engineered heart tissue platform for cardiotoxicity assessment.

Yao-Hui Sun1, Daphne A Diloretto2, Hillary K J Kao2

  • 1Division of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA; Department of Radiation Oncology, University of California, Davis, Sacramento, CA 95817, USA.

Stem Cell Reports
|March 20, 2026
PubMed
Summary

Researchers developed a novel engineered heart tissue model for assessing environmental toxin cardiotoxicity. This advanced platform offers a more sensitive and physiologically relevant method for drug screening and understanding heart disease risks.

Keywords:
calcium transientcardiac tissue engineeringcardiotoxicitydrug screeningethanolextracellular matrixhuman induced pluripotent stem cell-derived cardiomyocyteshuman induced pluripotent stem cellsrotenone.xenobiotics

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Area of Science:

  • Cardiovascular Research
  • Toxicology
  • Biomedical Engineering

Background:

  • Cardiovascular diseases (CVDs) are a major health concern, with environmental xenobiotics playing a significant role.
  • Existing in vitro models for cardiotoxicity assessment lack physiological relevance.
  • The impact of numerous potential toxicants on cardiovascular health remains largely unknown.

Purpose of the Study:

  • To develop a physiologically relevant in vitro model for assessing cardiotoxicity.
  • To create a scalable platform for evaluating the effects of environmental xenobiotics on the heart.
  • To enable real-time monitoring of cardiac function in response to toxicants.

Main Methods:

  • Development of a three-dimensional recellularized humanized engineered heart tissue (rHHT) platform.
  • Integration of decellularized human left ventricular extracellular matrix with human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
  • Generation of a hiPSC line expressing the calcium indicator GCaMP6f for monitoring calcium transients.

Main Results:

  • The rHHT platform successfully recapitulates key features of native ventricular myocardium.
  • The platform enables real-time and longitudinal monitoring of calcium transients.
  • Demonstrated higher sensitivity and stringency for cardiotoxicity assessment compared to conventional monolayer models using ethanol and rotenone.

Conclusions:

  • The developed rHHT platform is a scalable and sensitive system for xenobiotic cardiotoxicity assessment.
  • This platform has potential applications in high-throughput screening and mechanistic studies of cardiotoxicity.
  • The engineered heart tissue model holds promise for future personalized medicine applications in cardiovascular risk assessment.