Figure 5.

Transplantation with WT bone marrow rescues ischemia-induced angiogenic capillary branching in the MMP-9^−/− mice. Nonischemic tissues illustrate similar levels of capillary perfusion capacity in the WT or MMP-9^−/−. Left, Fluorescence microangiography. Middle, Increased perfusion capacity was detected in WT ischemic tissues, whereas MMP-9^−/− ischemic tissues showed an impaired perfusion (day 14), consistent with inadequate angiogenesis. Transplantation (Tx) of WT bone marrow to MMP-9^−/− mice (right) rescued perfusion capacity, as suggested by the high capillary tortuosity and branching in the MMP-9^−/− ischemic tissue (top right). All scale bars=100 μm. Bottom right, MMP-9 (red)–positive macrophages (green) were detected (arrows) at early time points in the MMP-9^−/− ischemic tissues of mice transplanted with WT marrow by double immunohistochemistry (scale bar=20 μm). Inset, Demonstration that macrophages (green) are bone marrow–derived because they are positive for the donor rare allele CD45.1 (red). All nuclei are counterstained with Hoechst (blue). Graph, Quantification of capillary branching by fluorescence microangiography confirms increased branching in WT (solid bar) ischemic tissue (P<0.05 vs nonischemic) and decreased branching in MMP-9^−/− (white bar) ischemic tissue (P<0.05 vs nonischemic) and demonstrates that transplantation (Tx) of WT bone marrow into MMP-9^−/− mice (striped) increases capillary branching in MMP-9^−/− ischemic tissues vs MMP-9^−/− nonischemic tissues (*P<0.05), as well as ischemic tissues of nontransplanted MMP-9^−/− (*P<0.05), bringing it to levels comparable to WT ischemic tissues (P=NS).