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EMBRYONIC STEM CELLS

Stromal Cell-Derived Factor-1/CXCR4 Signaling Modifies the Capillary-Like Organization of Human Embryonic Stem Cell-Derived Endothelium In Vitro

^aCenter for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA;
^cMaine Medical Center Research Institute, Scarborough, Maine, USA;
^bDepartment of Hematology, Huashan Hospital, Fudan University, Shanghai, China;
^dHarvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA

Key Words. Human embryonic stem cells • CXCR4 • Endothelial • Vascular development

Correspondence: Zack Z. Wang, Ph.D., Maine Medical Center Research Institute-Center for Regenerative Medicine & Technology, 81 Research Drive Scarborough, Maine 04074, USA. Telephone: 207-885-8313; Fax: 207-885-8179; e-mail: wangz{at}mmc.org

Received March 13, 2006; accepted for publication September 27, 2006.
First published online in STEM CELLS EXPRESS   October 12, 2006.



The molecular mechanisms that regulate human blood vessel formation during early development are largely unknown. Here we used human ESCs (hESCs) as an in vitro model to explore early human vasculogenesis. We demonstrated that stromal cell-derived factor-1 (SDF-1) and CXCR4 were expressed concurrently with hESC-derived embryonic endothelial differentiation. Human ESC-derived embryonic endothelial cells underwent dose-dependent chemotaxis to SDF-1, which enhanced vascular network formation in Matrigel. Blocking of CXCR4 signaling abolished capillary-like structures induced by SDF-1. Inhibition of the SDF-1/CXCR4 signaling pathway by AMD3100, a CXCR4 antagonist, disrupted the endothelial sprouting outgrowth from human embryoid bodies, suggesting that the SDF-1/CXCR4 axis plays a critical role in regulating initial vessel formation, and may function as a morphogen during human embryonic vascular development.

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