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Construction of Defined Human Engineered Cardiac Tissues to Study Mechanisms of Cardiac Cell Therapy
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Engineered heart slices for electrophysiological and contractile studies
Adriana Blazeski1, Geran M Kostecki1, Leslie Tung1
1Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Biomaterials
|May 3, 2015
Summary
Engineered heart slices (EHS) use decellularized cardiac tissue scaffolds to better mimic native heart tissue. This novel approach supports functional cell growth and electrical activity, advancing in vitro cardiac modeling.
Area of Science:
- Biomaterials Engineering
- Cardiovascular Research
- Tissue Engineering
Background:
- Faithfully replicating native tissue's complex topography and biochemistry is crucial for engineered cardiac tissues.
- Traditional cell cultures lack essential biochemical, structural, and mechanical cues from native extracellular matrix (ECM).
Purpose of the Study:
- To develop and characterize engineered heart slices (EHS) as a more physiologically relevant in vitro cardiac model.
- To evaluate the structural and functional properties of EHS cultured on decellularized cardiac ECM.
Main Methods:
- Rat or pig ventricular tissue was sectioned into 300 μm-thick disks and decellularized.
- Neonatal rat ventricular cells (NRVCs) were seeded onto the decellularized cardiac ECM slices to form EHS.
- Electrical pacing and optical mapping were used to assess tissue function and conduction properties.
Main Results:
- Decellularized ECM retained organized fiber structure, promoting NRVC alignment and anisotropic tissue formation.
- EHS demonstrated electrical pacing capabilities, anisotropic conduction (ratio ~2.0), and rate-dependent electrophysiological changes.
- Pace-induced reentrant arrhythmias were successfully generated and terminated in EHS.
Conclusions:
- Engineered heart slices (EHS) provide a valuable in vitro cardiac tissue model by incorporating native ECM cues.
- EHS offer improved structural and functional representation of cardiac tissue compared to traditional cell cultures.
- This model holds promise for studying cardiac electrophysiology and arrhythmia mechanisms.
