title: GM-CSF treated F4/80+ BMCs improve murine hind limb ischemia similar to M-CSF differentiated macrophages.
abstract: Novel cell therapy is required to treat critical limb ischemia (CLI) as many current approaches require repeated aspiration of bone marrow cells (BMCs). The use of cultured BMCs can reduce the total number of injections required and were shown to induce therapeutic angiogenesis in a murine model of hind limb ischemia. Blood flow recovery was significantly improved in mice treated with granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent BMCs that secreted inflammatory cytokines. Angiogenesis, lymphangiogenesis, and blood flow recovery ratio were significantly higher in the GM-CSF-cultured F4/80+ macrophage (GM-Mø)-treated group compared with controls. Furthermore, Foxp3+ cell numbers and tissue IL-10 concentrations were significantly increased compared with controls. There was no significant difference in blood flow recovery between GM-Mø and M-CSF-cultured F4/80+ macrophages (M-Mø). Thus, GM-Mø were associated with improved blood flow in hind limb ischemia similar to M-Mø. The selective methods of culturing and treating GM-Mø cells similar to M-Mø cells could be used clinically to help resolve the large number of cells required for BMC treatment of CLI. This study demonstrates a novel cell therapy for CLI that can be used in conjunction with conventional therapy including percutaneous intervention and surgical bypass.
authors.affiliation: Department of Cardiovascular Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Kuwahara
authors.affiliation: Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nishinakamura
authors.affiliation: Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Daibo
authors.initials: D
authors.lastname: Kojima
authors.affiliation: Department of Cardiovascular Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Tashiro
authors.affiliation: Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Shohta
authors.initials: S
authors.lastname: Kodama
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D004195:Disease Models, Animal; D005121:Extremities / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism / Q000628:therapy*; D042583:Lymphangiogenesis / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor