Bone marrow cells recruited through the neuropilin-1 receptor promote arterial formation at the sites of adult neoangiogenesis in mice
J. Clin. Invest. Serena Zacchigna, et al. 118:2062 doi:10.1172/JCI32832 [Go to this article.]

Figure 7
CD11b⁺ cells promote the formation of arterial vessels through a paracrine effect in concert with the activated endothelium. (A) In vivo arterial formation by the coinjection of AAV-VEGF₁₂₁ and CD11b⁺ cells. While AAV-VEGF₁₂₁ only promotes massive capillary sprouting, as shown by CD31 staining in green (upper left panel), the simultaneous administration of purified CD11b⁺ cells determines the formation of several arteries (α-SMA staining in red) in close proximity to the cellular infiltrates (white arrows). Scale bar: 100 μm. (B) Quantification of the relative areas occupied by cellular nuclei (DAPI), endothelial cells (CD31), or SMCs (α-SMA) in 20 independent sections for each treatment (AAV-VEGF₁₂₁, BM CD11b⁺ cells, or a combination of both). Data are presented as means ± SD. *Statistical significance over control, AAV-LacZ–treated muscles (P < 0.05). Cells, BM CD11b⁺ cells; C, control. (C) CD11b⁺ cell engraftment in the skeletal muscle. A large number of PKH26-labeled CD11b⁺ cells injected together with AAV-VEGF₁₂₁, could be detected in the skeletal muscle as red fluorescent cells at day 3 after injection (left panel). A lower number of cells were still present at longer time points (shown at 21 days on the right panel) in close proximity to arterial vessels (visualized in green by α-SMA immunofluorescence staining). Scale bar: 200 μm. (D) Effect of CD11b⁺ cells on VEGF₁₂₁-induced vascular leakiness. Shown are results of the Miles test as a measure of vascular permeability in muscles injected with AAV- VEGF₁₆₅ and VEGF₁₂₁ alone or in combination with CD11b⁺ cells. Data are presented as a ratio of the adsorbance for the treated and the contralateral mock-treated tibialis anterior muscle. A significant reduction in vascular leakiness was evident when CD11b⁺ cells had been coinjected with AAV-VEGF₁₂₁ as compared with AAV-VEGF₁₂₁ alone, reaching a value comparable to AAV-VEGF₁₆₅. No effect was observed by CD11b⁺ cell injection per se. *P < 0.05.