Title: CXCR4, a Key Modulator of Vascular Progenitor Cells
Abstract: 2][3] It is believed that the majority of vascular progenitor cells originate from the bone marrow.Stem cells within the bone marrow usually exist in a quiescent state.Specific signals stimulate the stem cells to differentiate and move to systemic circulation (Mobilization).Progenitors are recruited and stay at the site of vascular repair or neovascularization (Homing), where they differentiate into endothelial-like cells or smooth muscle-like cells (Differentiation) and proliferate (Proliferation).The molecular processes leading to their mobilization from the bone marrow and homing to the sites of vascular remodeling or neovascularization are not fully understood. 4,5 See pages 275 and 283In the current issue of Arteriosclerosis, Thrombosis, and Vascular Biology, two articles 6,7 provide new insights into the essential role of CXCR4, the receptor for stromal cellderived factor-1 (SDF-1) for the mobilization and the recruitment of bone marrow (BM)-derived cells.CXCR4 is notably expressed on hematopoietic stem cells and has previously been shown to play a key role in their homing and mobilization. 8Activation of this G protein-coupled 7-transmembrane receptor induces adhesion molecules on the hematopoietic progenitor/stem cell surface thereby enhancing their homing capacities 9 and regulating their proliferation. 10hiba et al 6 report that human recombinant macrophage colony stimulating factor (M-CSF) accelerated acute phase neointimal formation in a murine model of wire-mediated vascular injury.Consistent with previous reports, [11][12][13] the authors found that BM-derived cells substantially contributed to neointima formation.M-CSF is a proinflammatory cytokine constitutively expressed in normal arteries that regulates differentiation, proliferation, and survival of monocytes/macrophages 14 and smooth muscle cells. 15Interestingly, expression of M-CSF is upregulated in the injured artery 16 and implicated in the pathogenesis of atherosclerosis. 17,18In an attempt to obtain a clue to the mechanism by which M-CSF accelerated BM-derived cell accumulation in neointima, Shiba et al report high expression of SDF-1 as well as