Stromal cell-derived factor-1/CXCR4 signaling modifies the capillary-like organization of human embryonic stem cell-derived endothelium in vitro

Tong Chen, Hao Bai, Ying Shao, Melanie Arzigian, Viktor Janzen, Eyal Attar, Yi Xie, David T. Scadden, Zack Z. Wang

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)392-401
Number of pages10
JournalStem Cells
Volume25
Issue number2
DOIs
Publication statusPublished - Feb 2007
Externally publishedYes

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Keywords

  • CXCR4
  • Endothelial
  • Human embryonic stem cells
  • Vascular development

ASJC Scopus subject areas

  • Cell Biology

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