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Updated: Jun 12, 2026
Derivation of Cardiac Progenitor Cells from Embryonic Stem Cells
Published on: January 12, 2015
Endothelial cells regulate cardiomyocyte development from embryonic stem cells
Kang Chen1, Hao Bai, Melanie Arzigian
1Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Insights
Endothelial cells are crucial for generating cardiomyocytes from pluripotent stem cells. Receptor tyrosine kinase EphB4 signaling within endothelial cells regulates this process, essential for cardiac regeneration.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Developmental Biology
Background:
- The molecular mechanisms guiding pluripotent stem cell differentiation into cardiomyocytes remain largely undefined.
- Understanding the cellular environment that directs cardiomyogenesis is critical for regenerative medicine.
Purpose of the Study:
- To investigate the role of endothelial cells and EphB4 signaling in cardiomyocyte generation from embryonic stem cells.
- To elucidate the contribution of the endothelial niche to cardiac differentiation.
Main Methods:
- Utilized EphB4-null embryonic stem cells to assess cardiomyocyte differentiation.
- Employed angiogenic inhibitors (endostatin, angiostatin) to study endothelial cell involvement.
- Performed co-culture experiments with embryonic stem cells and human endothelial cells.
- Analyzed the expression of cardiac-specific genes (alpha-MHC, MLC-2V).
Main Results:
- EphB4-null embryonic stem cells showed significantly reduced cardiomyocyte formation and cardiac gene expression.
- Angiogenic inhibitors impaired endothelial cell differentiation and subsequent cardiomyogenesis.
- Co-culture with human endothelial cells enhanced cardiomyocyte generation and cardiac gene expression in embryonic stem cells.
- Human endothelial cells rescued the cardiomyocyte differentiation defects in EphB4-deficient embryonic stem cells.
Conclusions:
- Endothelial cells play an essential, previously unrecognized role in facilitating cardiomyocyte differentiation from pluripotent stem cells.
- EphB4 signaling within the endothelial niche is a critical regulator of cardiomyocyte regeneration.
Abstract:
The molecules and environment that direct pluripotent stem cell differentiation into cardiomyocytes are largely unknown. Here, we determined a critical role of receptor tyrosine kinase, EphB4, in regulating cardiomyocyte generation from embryonic stem (ES) cells through endothelial cells. The number of spontaneous contracting cardiomyocytes, and the expression of cardiac-specific genes, including alpha-MHC and MLC-2V, was significantly decreased in EphB4-null ES cells. EphB4 was expressed in endothelial cells underneath contracting cardiomyocytes, but not in cardiomyocytes. Angiogenic inhibitors, including endostatin and angiostatin, inhibited endothelial cell differentiation and diminished cardiomyogenesis in ES cells. Generation of functional cardiomyocytes and the expression of cardiac-specific genes were significantly enhanced by co-culture of ES cells with human endothelial cells. Furthermore, the defects of cardiomyocyte differentiation in EphB4-deficient ES cells were rescued by human endothelial cells. For the first time, our study demonstrated that endothelial cells play an essential role in facilitating cardiomyocyte differentiation from pluripotent stem cells. EphB4 signaling is a critical component of the endothelial niche to regulate regeneration of cardiomyocytes.
