CSF1-mediated macrophage recruitment enhances VEGF-induced angiogenesis.

<p>PEGDA hydrogels encapsulated with VEGF (320 ng), CSF1 (320 ng), VEGF (320 ng) + CSF1 (320 ng) or PDGFBB (320 ng) + FGF2 (80 ng) were implanted in <i>Csf1r-EGFP</i>^<i>+/tg</i> or <i>Flk1-myr</i>::<i>mCherry</i>^<i>+/tg</i> mice. Quantification of confocal images (a-d) indicated that the density of Csf1r-EGFP+ cells recruited by either CSF1 or CSF1/VEGF at day 3 was significantly higher than VEGF alone and similar to the density of PDGDBB/FGF2 (i). When comparing vessel density and total vessel length at day 10 (e-h), CSF1 alone was non-angiogenic. However, the combination of CSF1/VEGF induced a more robust angiogenic response compared to VEGF alone that was comparable to PDGFBB/FGF2 (j and k). When CSF1 was co-delivered with VEGF, the recruited macrophages not only improved the angiogenic response, but also enhanced pericyte investment on VEGF-induced vessels (o-q), similar to PDGFBB/FGF2 induced vessels (l-n). Abbreviations: VEGF (V); CSF1 (C); VEGF+CSF1 (V+C); PDGFBB+FGF2 (P+F).