Muscle-derived Gr1(dim)CD11b(+) cells enhance neovascularization in an ischemic hind limb mouse model.
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.
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, 46202, USA.
Jeong A
JA
Kim
Keith
K
March
Hee-Don
HD
Chae
Brian
B
Johnstone
Su-Jung
SJ
Park
Todd
T
Cook
Stephanie
S
Merfeld-Clauss
Hal E
HE
Broxmeyer
D000818:Animals; D015153:Blotting, Western; D039481:CD11b Antigen / Q000378:metabolism*; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006614:Hindlimb / Q000098:blood supply* / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000235:genetics; D019707:Receptors, Chemokine / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D012333:RNA, Messenger; D019707:Receptors, Chemokine