Muscle-derived Gr1(dim)CD11b(+) cells enhance neovascularization in an ischemic hind limb mouse model.

Abstract

Gr1(+)CD11b(+) cells are characterized as myeloid-derived suppressor cells potentially involved in angiogenesis. We demonstrate that Gr1(+)CD11b(+) cells isolated from ischemic muscle in a hind-limb ischemic C57BL/6 mouse model play a role in vessel formation after ischemic injury. Gr1(dim)CD11b(+) cells, a subpopulation of Gr1(+)CD11b(+) cells, within skeletal muscle were increased in context of ischemia. Strikingly, astrocyte-plexus formed from muscle-derived Gr1(dim)CD11b(+) cells in Matrigel culture, followed by formation of isolectin and von Willebrand Factor-expressing cells, similar to that reported for angiogenesis in retina. When isolated muscle-derived Gr1(dim)CD11b(+) cells were injected into ischemic muscles, recovery of blood flow was significantly enhanced and these cells were incorporated into vessel walls. This suggests that Gr1(dim)CD11b(+) cells are recruited into ischemic regions after ischemia and may be involved in angiogenesis by their capacity to generate vascular cells.