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Updated: Jul 17, 2026
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Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells
Published on: November 1, 2017
Differential requirements for hematopoietic commitment between human and rhesus embryonic stem cells.
Deepika Rajesh1, Nachimuthu Chinnasamy, Shoukhrat M Mitalipov
1Department of Surgery, University of Wisconsin Medical School, K4/760 Clinical Science Center, 600 Highland Avenue, Madison, Wisconsin 53792-7375, USA.
Stem Cells (Dayton, Ohio)
|February 8, 2007
Summary
Rhesus macaque ESCs (rESCs) show limited hematopoietic differentiation compared to human ESCs (hESCs), pausing at the hemangioblast stage. This study highlights key differences crucial for advancing stem cell transplantation therapies.
Area of Science:
- Stem Cell Biology
- Hematopoiesis
- Comparative Biology
Background:
- Clinical application of ESC-derived hematopoietic transplantation requires large animal models.
- Rhesus macaque ESCs (rESCs) have shown limited hematopoietic differentiation compared to human ESCs (hESCs).
- Understanding these differences is key to advancing ESC-based therapies.
Purpose of the Study:
- To compare hematopoietic differentiation between hESCs and rESCs.
- To identify functional differences in ESC hematopoietic development.
- To clarify critical steps in ESC hematopoietic differentiation.
Main Methods:
- Adapted hESCs and rESCs to Matrigel culture.
- Compared differentiation in OP9 stroma coculture and EB culture with cytokines.
- Analyzed cell surface markers (CD34, CD45) and colony formation in methylcellulose.
Main Results:
- rESCs in OP9 stroma produced CD34(+)CD45(-) cells forming endothelial networks, unlike hESCs which showed robust hematopoietic differentiation.
- Cytokine-supplemented EB culture improved rESC hematopoietic differentiation but levels remained lower than hESCs.
- rESCs formed mixed colonies of erythroid, myeloid, and endothelial cells, indicating bipotential hematoendothelial progenitors.
Conclusions:
- rESCs possess hematopoietic potential but pause at the hemangioblast stage in conditions optimized for hESCs.
- Functional differences between hESCs and rESCs impede direct translation of differentiation protocols.
- Further research is needed to overcome rESC differentiation barriers for allogeneic transplantation models.
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