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Embryonic Stem Cells |
1 Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China
2 Maine Medical Center Research Institute, Scarborough, Maine
3 Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
4 Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China
5 Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts
6 Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Maine Medical Center Research Institute, Scarborough, Maine
* To whom correspondence should be addressed. E-mail: wangz{at}mmc.org.
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Abstract |
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The molecular mechanisms that regulate human blood vessel formation during early development are largely unknown. Here we used human embryonic stem cells (hESCs) as an in vitro model to explore early human vasculogenesis. We demonstrated that 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 (EBs), 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.
Key Words. human embryonic stem cells, CXCR-4, endothelial, vascular development
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