VEGF-Induced Adult Neovascularization: Recruitment, Retention, and Role of Accessory Cells

• Published in: Cell 2006-01, Vol.124 (1), p.175-189
• Main Authors: Grunewald, Myriam, Avraham, Inbal, Dor, Yuval, Bachar-Lustig, Esther, Itin, Ahuva, Yung, Steffen, Chimenti, Stephano, Landsman, Limor, Abramovitch, Rinat, Keshet, Eli
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - physiology; Chemokine CXCL12; Chemokines, CXC - physiology; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - physiology; Heart - drug effects; Heart - physiology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - physiology; Liver - drug effects; Liver - physiology; Mice; Mice, Inbred NOD; Mice, SCID; Mice, Transgenic; Myeloid Cells - drug effects; Myeloid Cells - physiology; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Organ Specificity - genetics; Organ Specificity - physiology; Vascular Endothelial Growth Factor A - pharmacology; Vascular Endothelial Growth Factor A - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2005.10.036

Adult neovascularization relies on the recruitment of circulating cells, but their angiogenic roles and recruitment mechanisms are unclear. We show that the endothelial growth factor VEGF is sufficient for organ homing of circulating mononuclear myeloid cells and is required for their perivascular positioning and retention. Recruited bone marrow-derived circulating cells (RBCCs) summoned by VEGF serve a function distinct from endothelial progenitor cells. Retention of RBCCs in close proximity to angiogenic vessels is mediated by SDF1, a chemokine induced by VEGF in activated perivascular myofibroblasts. RBCCs enhance in situ proliferation of endothelial cells via secreting proangiogenic activities distinct from locally induced activities. Precluding RBCCs strongly attenuated the proangiogenic response to VEGF and addition of purified RBCCs enhanced angiogenesis in excision wounds. Together, the data suggest a model for VEGF-programmed adult neovascularization highlighting the essential paracrine role of recruited myeloid cells and a role for SDF1 in their perivascular retention.