Epo has direct effects on resident vasculature, and it mobilizes circulating CD34+ BM-derived populations to stimulate their contribution to vascular repair in both acute and chronic injury models. BM-derived EPCs circulate in the bloodstream and migrate to areas of ischemia, respond to hypoxia-regulated factors such as Epo, and participate in both physiological and pathological neovascularization. Epo stimulates EPC proliferation, adhesion, and differentiation to endothelium, as do other hypoxia-regulated factors such as VEGF, stromal cell–derived factor 1 (SDF-1), and insulin-like growth factor–binding protein 3 (IGFBP-3).