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Developing 3D Organized Human Cardiac Tissue within a Microfluidic Platform
Published on: June 15, 2021
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Development of a drug screening system using three-dimensional cardiac tissues containing multiple cell types.
Maki Takeda1, Shigeru Miyagawa1, Emiko Ito1
1Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Scientific Reports
|March 12, 2021
Summary
Optimizing the ratio of cardiac cells in three-dimensional cardiac tissues (3D-CTs) is crucial for drug screening. A specific composition (7CT) demonstrated superior contractility and drug sensitivity, making it ideal for detecting drug-induced arrhythmia.
Area of Science:
- Biomaterials Science
- Cardiovascular Research
- Drug Discovery
Background:
- Developing reliable three-dimensional cardiac tissues (3D-CTs) for drug screening requires precise cellular composition.
- Extracellular matrix (ECM) and cell ratios significantly influence cardiac tissue function and drug response.
Purpose of the Study:
- To determine the optimal ratio of cardiomyocytes, fibroblasts, and endothelial cells for functional 3D-CTs.
- To evaluate the efficacy of different 3D-CT compositions as drug screening platforms.
Main Methods:
- Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), cardiac fibroblasts (CFs), and cardiac endothelial cells (CEs) were combined in varying ratios (10:0:0, 7:2:1, 5:4:1, 2:7:1).
- Gene expression (cardiac, fibroblast, endothelial, ECM, adhesion, ion channel markers) and protein expression were analyzed.
- Contractile properties were assessed, and drug responses to E-4031 and isoproterenol were evaluated.
Main Results:
- Increased fibroblast proportion correlated with higher ECM/adhesion gene expression and lower ion channel gene expression.
- The 7:2:1 (7CT) ratio exhibited the greatest contractility.
- 7CT and 5CT showed reduced contractility and QT prolongation with E-4031; 7CT demonstrated the highest drug sensitivity and response to isoproterenol.
Conclusions:
- Three-dimensional cardiac tissues with optimized fibroblast and endothelial cell ratios (e.g., 7CT) are effective for drug screening.
- These engineered tissues can accurately detect drug-induced arrhythmia and assess drug efficacy.
