Role of c-kit/Kit ligand signaling in regulating vasculogenesis

Summary

Mobilization into peripheral blood of bone marrow-derived cells including hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs), is regulated by chemokines/cytokines. These cells can contribute to the formation of new blood vessels (vasculogenesis) under pathological conditions including atherosclerosis, wound healing and tumor growth. We will review how these cells are mobilized into circulation, and supplied to the sites, where vessel formation is needed (i.e. ischemic tissue or tumor bed).We will give evidence that matrix metalloproteinase-9 mediated Kit ligand (Stem cell factor) processing is essential for cell mobilization induced by chemo-/cyto-kines, like vascular endothelial growth factor (VEGF), Placental growth factor (PlGF), stromal cell derived factor-1 (SDF-1). These studies may provide the basis for the development of new therapeutic strategies for vascular diseases through targeting kit ligand mediated mobilization and homing of bone marrow-derived progenitor cells for cell therapy and cancer therapy.

This publication was partially financed by Serono Foundation for the Advancement of Medical Science. Financial support: This work was supported by a grant from the Japanese Society for the Promotion of Science (B.H.) and by funds from the National Institutes of Health (CA 72006 and AR46238 to ZW). Part of this paper was originally presented at the 2^nd International Workshop on New Therapeutic Targets in Vascular Biology from February 6-9, 2003 in Geneva, Switzerland.

Keywords

Matrix metalloproteinase-9 - endothelial progenitor cells - tyrosine kinase receptor - stem cells - vasculogenesis

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