Related Experiment Video
Updated: Sep 20, 2025
Induction of Myocardial Infarction and Myocardial Ischemia-Reperfusion Injury in Mice
Published on: January 19, 2022
Human Heart Anoxia and Reperfusion Tissue (HEART) Model for the Rapid Study of Exosome Bound miRNA Expression As
Bradley W Ellis1, George Ronan1, Xiang Ren2
1Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN, 46556, USA.
Abstract:
Current biomarkers for myocardial infarction (MI) diagnosis are typically late markers released upon cell death, incapable of distinguishing between ischemic and reperfusion injury and can be symptoms of other pathologies. Circulating microRNAs (miRNAs) have recently been proposed as alternative biomarkers for MI diagnosis; however, detecting the changes in the human cardiac miRNA profile during MI is extremely difficult. Here, to study the changes in miRNA levels during acute MI, a heart-on-chip model with a cardiac channel, containing human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes in human heart decellularized matrix and collagen, and a vascular channel, containing hiPSC-derived endothelial cells, is developed. This model is exposed to anoxia followed by normoxia to mimic ischemia and reperfusion, respectively. Using a highly sensitive miRNA biosensor that the authors developed, the exact same increase in miR-1, miR-208b, and miR-499 levels in the MI-on-chip and the time-matched human blood plasma samples collected before and after ischemia and reperfusion, is shown. That the surface marker profile of exosomes in the engineered model changes in response to ischemic and reperfusion injury, which can be used as biomarkers to detect MI, is also shown. Hence, the MI-on-chip model developed here can be used in biomarker discovery.
Insights
A novel heart-on-chip model accurately detects microRNA (miRNA) changes during myocardial infarction (MI), mirroring human blood plasma. This breakthrough aids in discovering new biomarkers for early MI detection and distinguishing injury types.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Biomarker Discovery
Background:
- Current myocardial infarction (MI) biomarkers are late indicators of cell death and cannot differentiate ischemia from reperfusion injury.
- Circulating microRNAs (miRNAs) show promise as early MI biomarkers, but detecting cardiac miRNA changes in patients is challenging.
Purpose of the Study:
- To develop and validate a heart-on-chip model for studying miRNA dynamics during acute MI.
- To identify specific cardiac miRNAs and exosome surface markers indicative of MI and reperfusion injury.
Main Methods:
- Engineered a heart-on-chip model with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and endothelial cells in a biomimetic matrix.
- Subjected the model to anoxia/normoxia cycles to simulate ischemia/reperfusion (MI).
- Utilized a sensitive miRNA biosensor to quantify miRNA levels in the chip and matched human plasma samples.
Main Results:
- The MI-on-chip model demonstrated synchronized increases in miR-1, miR-208b, and miR-499 levels, consistent with human plasma samples post-ischemia/reperfusion.
- Changes in exosome surface marker profiles within the engineered model were observed in response to ischemic and reperfusion injury.
- The model successfully mimicked cardiac miRNA alterations seen in acute MI patients.
Conclusions:
- The developed heart-on-chip model serves as a powerful platform for MI biomarker discovery.
- This model can accurately reflect in vivo cardiac miRNA changes, facilitating the identification of novel diagnostic markers.
- The findings suggest that both specific miRNAs and exosome profiles are potential biomarkers for detecting MI and reperfusion injury.
