Article

  • The EMBO Journal (1999) 18, 3964 - 3972
  • doi:10.1093/emboj/18.14.3964

VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells

Takayuki Asahara1, Tomono Takahashi1, Haruchika Masuda1, Christoph Kalka1, Donghui Chen1, Hideki Iwaguro1, Yoko Inai1, Marcy Silver1 and Jeffrey M. Isner1

  1. Departments of Medicine (Cardiology) and Biomedical Research, St Elizabeth's Medical Center, Tufts University School of Medicine, 736 Cambridge Street, Boston, MA 02135, USA

Correspondence to:

Takayuki Asahara, E-mail: asa777@aol.com

Jeffrey M. Isner, E-mail: jisner@opal.tufts.edu

Received 27 January 1999; Accepted 19 May 1999; Revised 29 April 1999


Vascular endothelial growth factor (VEGF) has been shown to promote neovascularization in animal models and, more recently, in human subjects. This feature has been assumed to result exclusively from its direct effects on fully differentiated endothelial cells, i.e. angiogenesis. Given its regulatory role in both angiogenesis and vasculogenesis during fetal development, we investigated the hypothesis that VEGF may modulate endothelial progenitor cell (EPC) kinetics for postnatal neovascularization. Indeed, we observed an increase in circulating EPCs following VEGF administration in vivo. VEGF-induced mobilization of bone marrow-derived EPCs resulted in increased differentiated EPCs in vitro and augmented corneal neovascularization in vivo. These findings thus establish a novel role for VEGF in postnatal neovascularization which complements its known impact on angiogenesis.

  • Keywords:

    • blood,
    • bone marrow,
    • endothelial progenitor cell,
    • vascular endothelial growth factor,
    • vasculogenesis