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Human iPSC-Derived Cardiomyocyte Networks on Multiwell Micro-electrode Arrays for Recurrent Action Potential Recordings
Published on: July 15, 2019
Conduction analysis in mixed cardiomyocytes-fibroblasts cultures using microelectrode arrays
Shilpi Roy1, Michael Q Chen, Gregory T A Kovacs
1Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA. shilpir@stanford.edu
Summary
Developing an in-vitro cardiac arrhythmia model requires understanding electrical conduction in mixed cell cultures. A minimum of 70% cardiomyocytes is needed for electrical activity, but higher ratios ensure uniform wave propagation for accurate arrhythmia studies.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Cellular Electrophysiology
Background:
- Current cardiac arrhythmia models are limited to in vivo and computational approaches.
- In vitro models are needed for detailed study of electrical conduction in cardiac tissue.
- Heterogeneous cell cultures present unique challenges for understanding action potential propagation.
Purpose of the Study:
- To investigate the impact of cardiomyocyte and fibroblast ratios on electrical conduction in vitro.
- To determine the minimum cell composition necessary for detecting electrical activity in mixed cultures.
- To assess the feasibility of creating a homogeneous depolarization wave for in vitro cardiac models.
Main Methods:
- Culturing mixed cardiomyocyte-fibroblast populations on microelectrode arrays (500x500 microm, 36 electrodes).
- Systematically varying the ratios of cardiomyocytes to fibroblasts.
- Monitoring and analyzing action potential propagation patterns across the cultures.
Main Results:
- A minimum ratio of 70% cardiomyocytes to 30% fibroblasts was required for detectable electrical activity.
- Higher cardiomyocyte proportions (e.g., 90:10) were insufficient for consistently achieving uniform, unidirectional depolarization waves.
- Tissue homogeneity is critical for supporting continuous electrical conduction, mimicking physiological conditions.
Conclusions:
- This study highlights the sensitivity of electrical conduction to tissue composition in vitro.
- The findings are crucial for developing reliable in vitro models of cardiac arrhythmia, particularly reentry phenomena.
- The results have implications for stem cell-based cardiac grafts and tissue engineering.
