Related Experiment Video
Updated: May 24, 2026
14:03
High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers
Published on: March 24, 2023
A cell-based phenotypic assay to identify cardioprotective agents
Stephanie Guo1, Adam Olm-Shipman, Andrew Walters
1School of Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA.
Circulation Research
|March 8, 2012
Summary
A new 24-well cell-based assay effectively models tissue ischemia/reperfusion (IR) injury. This high-throughput screening method accurately predicts molecule effects on cardiac function and infarct size in the heart.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Cellular Biology
Background:
- Ischemia/reperfusion (IR) injury is a major cause of death, linked to heart attack and stroke.
- Current IR injury models are not suitable for high-throughput screening (HTS), hindering therapeutic development.
Purpose of the Study:
- To develop a physiologically relevant and HTS-amenable model for IR injury.
- To screen molecules for their effects on IR injury.
Main Methods:
- A 24-well microplate respirometry system was adapted to create transient IR injury in H9c2 cardiomyocytes.
- A library of 2000 molecules was screened using cell death as an endpoint, with Po2 and pH monitoring for metabolic data.
- Promising molecules were validated in a Langendorff-perfused heart model.
Main Results:
- The cell-based assay demonstrated strong correlations with recovery of cardiac function (r2=0.66) and infarct size (r2=0.62) in the heart model.
- Screening identified protective, detrimental, and inert molecules.
- Cellular bioenergetics were linked to protection against IR injury.
Conclusions:
- A novel cell-based assay accurately predicts the impact of molecules on IR injury in the intact heart.
- This HTS model can accelerate the identification of potential therapeutics or harmful compounds for IR injury.
