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Updated: May 17, 2026
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Construction of Defined Human Engineered Cardiac Tissues to Study Mechanisms of Cardiac Cell Therapy
Published on: March 1, 2016
Genetic engineering of somatic cells to study and improve cardiac function
Robert D Kirkton1, Nenad Bursac
1Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Summary
Genetically engineered excitable cells enhance cardiac tissue function by improving electrical conduction and mechanical force. This platform aids in studying electrophysiology, validating models, and developing therapies for heart conditions.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Cellular Electrophysiology
Background:
- Engineered cardiac tissues are crucial for studying heart function and disease.
- Mimicking fibrotic myocardium's slow action potential (AP) conduction is challenging.
- Neonatal rat ventricular myocytes (NRVMs) are commonly used but have limitations.
Purpose of the Study:
- To demonstrate the utility of genetically engineered excitable cells for electrophysiology studies.
- To enhance the electrical and mechanical function of engineered cardiac tissues.
- To create a novel platform for cardiac cell therapy research.
Main Methods:
- Micropatterning NRVMs on elastomeric films to mimic fibrotic myocardium.
- Co-culturing NRVMs with genetically engineered human embryonic kidney (HEK-293) cells expressing specific ion channels (Ex-293).
- Expressing mutant Na(v)1.5 channels, Ca(v)3.3 channels (ExCa-293), and optogenetic constructs (ChIEF) in HEK-293 cells.
Main Results:
- Engineered excitable cells (Ex-293) increased cardiac conduction velocity by 370% and twitch force by 64%.
- Mutant Na(v)1.5 channels propagated APs similarly to wild-type despite reduced sodium current.
- ExCa-293 cells improved AP duration and reduced repolarization gradients; optogenetics enabled light-controlled AP firing.
Conclusions:
- Genetically engineered excitable cells significantly improve engineered cardiac tissue function, despite being non-contractile.
- This platform is valuable for tissue-level electrophysiology studies and cardiac channelopathy research.
- Future applications include high-throughput screening, model validation, and developing somatic cell therapies for cardiac infarction and arrhythmias.
