Selective homing of EPCs to ischemic tissue. Bone marrow–derived EPCs, identified by lacZ expression, were noted to be preferentially recruited to zones of severe ischemia. (A) (B) (C) (D) (E) Histologic sections taken along the axis of ischemia at day 7 are shown (panel A), with close-up views of the nonischemic (panel B) and ischemic (panel C) portions of the skin; lacZ⁺ EPCs stain blue and are highlighted with arrows. Transverse sections taken from the central portion of ischemic tissue at day 7 (panel D) reveal a considerable number of lacZ⁺ EPCs within the ischemic (panel E), but not incised, skin; (scale bars = 50 μm). (F) The number of lacZ⁺ EPCs recruited to regions of ischemia at day 7 was found to correlate inversely with the degree of ischemia; tissue sections were divided into zones of mild, moderate, and severe ischemia. (G) Human EPCs were then studied under hypoxic conditions in vitro and were noted to be significantly more adherent to endothelial monolayers exposed to 0.5% O₂. (H) EPC chemotaxis was also studied by harvesting media from hypoxic cultures of endothelial cells and fibroblasts, and EPC migration toward hypoxic media (0.5% O₂) from both cell types was significantly increased.