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Updated: Aug 11, 2026
Epicardial Outgrowth Culture Assay and Ex Vivo Assessment of Epicardial-derived Cell Migration
Published on: March 18, 2016
Human pluripotent stem cell-derived epicardial progenitors can differentiate to endocardial-like endothelial cells
Xiaoping Bao1, Vijesh J Bhute1, Tianxiao Han1
1Dept. of Chemical & Biological Engineering, University of Wisconsin, Madison, WI 53706 53706, USA.
Insights
Human epicardial progenitors can generate endocardium-like endothelial cells. This discovery advances understanding of heart development and cardiac tissue engineering applications.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Stem Cell Biology
Background:
- Epicardial progenitors are crucial for heart development, forming various cardiac cell types.
- The specific contribution of human epicardial progenitors to the endothelium remains unclear, hindering research.
Purpose of the Study:
- To investigate the potential of human pluripotent stem cell (hPSC)-derived epicardial cells to generate endothelial cells.
- To characterize the properties of these derived endothelial cells.
Main Methods:
- Generation of CDH5-2A-eGFP knock-in hPSC lines for epicardial cell differentiation.
- Induction of endothelial cell formation from WT1+ epicardial cells using VEGF treatment.
- Analysis of WT1 expression correlation with endothelial cell generation.
Main Results:
- Successfully differentiated hPSCs into self-renewing WT1+ epicardial cells.
- Demonstrated that these epicardial cells yield endothelial cells upon VEGF stimulation.
- Characterized the resulting endothelial cells as possessing endocardium-like properties, including specific markers and tight junctions.
Conclusions:
- Human epicardial progenitors possess the capacity to form endocardial endothelium.
- Findings have significant implications for heart regeneration strategies and cardiac tissue engineering.
- Established a novel method for studying human epicardial cell differentiation and function.
Abstract:
During heart development, epicardial progenitors contribute various cardiac lineages including smooth muscle cells, cardiac fibroblasts, and endothelial cells. However, their specific contribution to the human endothelium has not yet been resolved, at least in part due to the inability to expand and maintain human primary or pluripotent stem cell (hPSC)-derived epicardial cells. Here we first generated CDH5-2A-eGFP knock-in hPSC lines and differentiated them into self-renewing WT1+ epicardial cells, which gave rise to endothelial cells upon VEGF treatment in vitro. In addition, we found that the percentage of endothelial cells correlated with WT1 expression in a WT1-2A-eGFP reporter line. The resulting endothelial cells displayed many endocardium-like endothelial cell properties, including high expression levels of endocardial-specific markers, nutrient transporters and well-organized tight junctions. These findings suggest that human epicardial progenitors may have the capacity to form endocardial endothelium during development and have implications for heart regeneration and cardiac tissue engineering.
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