Differential BM contribution results from activation of redundant mechanisms of postnatal neovasculogenesis. Combinations of models of adult neovasculogenesis were established in single mice and result in different levels of BM contribution. (A-B) Lewis lung carcinoma cell (LLC)–based tumors showed GFP⁺ bone marrow (BM) contribution throughout the tumor mass (A; scale bar represents 100 μm) mainly from CD11b⁺ cells (B; n = 8; scale bar represents 50 μm). Tumors are outlined with dashed lines. (C-D) Within tumor-associated vasculature, CD31 (C) and claudin-5 (D) staining showed integration from GFP⁺ BM cells (scale bars represent 20 μm). (E) B16 tumors had low levels of GFP⁺ BM contribution in comparison with all other models and no contribution within tumor-associated vasculature (n = 8; scale bar represents 100 μm). (F) The most robust contribution was seen in the retinal injury model. This model uses vascular endothelial growth factor (VEGF) overexpression by a recombinant adeno-associated virus type 2 that overexpresses the murine 188 isoform of VEGF-A (rAAV2 VEGF-A 188) and laser-induced ischemic injury to promote robust BM-derived neovascularization. DsRed⁺ BM-derived blood vessels are shown (middle panel) along with a negative control (left panel; scale bars represent 100 μm). All animals were perfused with FITC-dextran to show functional vasculature (right panel; n = 5; scale bar represents 50 μm). Similar results were observed with GFP⁺ BM (data not shown). (G) Retinas were costained with α-SMA to confirm endothelial phenotype (n = 5; scale bar represents 50 μm). (H) LLC tumors established in mice that received a transplant of DsRed⁺ BM along with retinal injury also showed BM integration into tumor vasculature (n = 5; scale bar represents 20 μm). Confocal microscopy with 0.5-micron Z-step analysis was necessary to identify nucleated cells coexpressing donor GFP or DsRed and endothelial proteins (CD31).