CD34+ bone marrow–derived progenitor cells contribute to tissue repair by differentiating into endothelial cells, vascular smooth muscle cells, hematopoietic cells, and possibly other cell types. However, the mechanisms by which circulating progenitor cells home to remodeling tissues remain unclear. Here we show that integrin α4β1 (VLA-4) promotes the homing of circulating progenitor cells to the α4β1 ligands VCAM and cellular fibronectin, which are expressed on actively remodeling neovasculature. Progenitor cells, which express integrin α4β1, homed to sites of active tumor neovascularization but not to normal nonimmune tissues. Antagonists of integrin α4β1, but not other integrins, blocked the adhesion of these cells to endothelia in vitro and in vivo as well as their homing to neovasculature and outgrowth into differentiated cell types. These studies describe an adhesion event that facilitates the homing of progenitor cells to the neovasculature.
Hui Jin, Aparna Aiyer, Jingmei Su, Per Borgstrom, Dwayne Stupack, Martin Friedlander, Judy Varner
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