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Updated: Nov 3, 2025

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Directed Differentiation of Hemogenic Endothelial Cells from Human Pluripotent Stem Cells
Published on: March 31, 2021
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The next generation of endothelial differentiation: Tissue-specific ECs
Jane Nguyen1, Ying-Yu Lin1, Sharon Gerecht2
1Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology, Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA.
Cell Stem Cell
|June 3, 2021
Summary
Human pluripotent stem cells (hPSCs) offer a powerful tool to generate diverse endothelial cells (ECs) for improved disease modeling and therapeutics. This review covers hPSC differentiation strategies and their applications in organoids and organ-on-chip systems.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Vascular Biology
Background:
- Endothelial cells (ECs) are crucial for regulating immune cell trafficking and respond to hemodynamic forces.
- ECs display significant tissue-specific heterogeneity despite a common mesodermal origin.
- Existing disease models and therapeutic strategies require enhanced accuracy and breadth, necessitating novel approaches to study ECs.
Purpose of the Study:
- To review current methodologies for differentiating human pluripotent stem cells (hPSCs) into various types of blood vascular ECs.
- To discuss the maturation of hPSC-derived ECs into continuous, fenestrated, and sinusoidal endothelial tissues.
- To explore the application of hPSC-derived ECs in advancing organoid development and organ-on-chip technologies.
Main Methods:
- Review of literature on hPSC differentiation protocols for EC generation.
- Analysis of strategies for EC maturation into distinct vascular phenotypes.
- Examination of studies utilizing hPSC-derived ECs in organoid and organ-on-chip models.
Main Results:
- hPSCs can be differentiated into a range of blood vascular ECs, capturing endothelial heterogeneity.
- Maturation protocols enable the generation of continuous, fenestrated, and sinusoidal ECs from hPSCs.
- hPSC-derived ECs are increasingly used in sophisticated organoid and organ-on-chip platforms.
Conclusions:
- hPSC-derived ECs represent a promising avenue for creating accurate and versatile models of human vascular biology.
- These cells hold significant potential for advancing the development of novel therapeutics and understanding vascular diseases.
- The integration of hPSC-derived ECs into organoid and organ-on-chip systems is revolutionizing preclinical research.

