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Updated: Mar 6, 2026
Fabrication of 3D Cardiac Microtissue Arrays using Human iPSC-Derived Cardiomyocytes, Cardiac Fibroblasts, and Endothelial Cells
Published on: March 14, 2021
Three-dimensional cardiac microtissues composed of cardiomyocytes and endothelial cells co-differentiated from human
Elisa Giacomelli1, Milena Bellin1, Luca Sala1
1Department of Anatomy and Embryology, Leiden University Medical Center, Leiden 2333ZC, The Netherlands.
Insights
Researchers developed a 3D human cardiac microtissue model integrating cardiomyocytes and endothelial cells. This advanced stem cell platform enables robust cardiovascular disease modeling and drug testing in vitro.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Biomedical Engineering
Background:
- Cardiomyocytes and endothelial cells engage in critical crosstalk influencing heart function.
- Existing in vitro cardiac models often lack this crucial cell-cell interaction, limiting physiological relevance.
- Developing predictive models requires recapitulating the native cardiac microenvironment.
Purpose of the Study:
- To generate and characterize human cardiac microtissues in vitro that integrate both cardiomyocytes and endothelial cells.
- To establish a robust and reproducible stem cell-based platform for cardiovascular disease modeling.
- To enable effective drug testing for cardiovascular conditions.
Main Methods:
- Simultaneous differentiation of cardiomyocytes and endothelial cells from human pluripotent stem cells.
- Cardiac mesoderm induction followed by cell enrichment based on surface markers.
- Recombination of cell populations to form beating 3D cardiac microtissues.
Main Results:
- Successfully generated 3D cardiac microtissues incorporating both cell types.
- Cardiac endothelial cells expressed relevant markers, indicating cardiac endothelium identity.
- The model demonstrated robustness and reproducibility using both embryonic and induced pluripotent stem cells.
Conclusions:
- The developed cardiac microtissue is an advanced in vitro model for studying cardiomyocyte-endothelium crosstalk.
- This platform offers a powerful tool for cardiovascular disease modeling and therapeutic screening.
- The model's reproducibility supports its utility in preclinical research and drug development.
Abstract:
Cardiomyocytes and endothelial cells in the heart are in close proximity and in constant dialogue. Endothelium regulates the size of the heart, supplies oxygen to the myocardium and secretes factors that support cardiomyocyte function. Robust and predictive cardiac disease models that faithfully recapitulate native human physiology in vitro would therefore ideally incorporate this cardiomyocyte-endothelium crosstalk. Here, we have generated and characterized human cardiac microtissues in vitro that integrate both cell types in complex 3D structures. We established conditions for simultaneous differentiation of cardiomyocytes and endothelial cells from human pluripotent stem cells following initial cardiac mesoderm induction. The endothelial cells expressed cardiac markers that were also present in primary cardiac microvasculature, suggesting cardiac endothelium identity. These cell populations were further enriched based on surface markers expression, then recombined allowing development of beating 3D structures termed cardiac microtissues. This in vitro model was robustly reproducible in both embryonic and induced pluripotent stem cells. It thus represents an advanced human stem cell-based platform for cardiovascular disease modelling and testing of relevant drugs.
