ABSTRACT
Introduction ................................................................................................ 163 Vascular progenitors support post-natal angiogenic processes ........ 164 Evidence for contributions of endothelial progenitors to tumor angiogenesis in humans ........................................................................... 165 Roles of co-mobilized hematopoietic cells in regulation of tumor angiogenesis ........................................................... 166 Angiogenic factors promote mobilization of VEGFR1+ hematopoietic cells through MMP-9-mediated release of soluble Kit ligand .................................................................... 170 Angiogenic factors recruit hematopoietic stem and progenitor cells through VEGFR1 activation........................................ 171 Conclusions................................................................................................. 173 Future directions ........................................................................................ 173 References .................................................................................................. 174
Introduction Compelling evidence suggests that recruitment of circulating vascular and hematopoietic stem and progenitor cells contributes to the initiation and
sustenance of post-natal neo-angiogenic processes. Co-mobilization of subsets of hematopoietic and vascular cells, collectively referred to as hemangiogenic cells, supports revascularization of ischemic limbs and tumor growth (Figure 8.1*). Several studies have indicated that bone marrow (BM)-derived hemangiogenic stem cells and their progeny functionally contribute to neo-angiogenesis during wound healing,1-6 post-myocardial ischemia,7-12 cerebral ischemia,13 limb ischemia,14-18 endothelialization of vascular grafts,19-22 atherosclerosis,23 retinal neovascularization,24,25 and tumor growth.3,26-32
In addition, the absolute numbers of circulating hemangiogenic progenitor cells have been demonstrated to correlate with the degree of neo-angiogenesis. The quantifications of the circulating hemangiogenic cells provide for novel biological surrogate markers to access responses to anti-angiogenesis therapy. This chapter summarizes the molecular and cellular pathways that support mobilization and recruitment of marrow-derived cells to the neo-angiogenic niches, thereby accelerating vascularization of ischemic limbs and tumor tissue.
