title: Additive effect of endothelial progenitor cell mobilization and bone marrow mononuclear cell transplantation on angiogenesis in mouse ischemic limbs.
abstract: The methods of therapeutic angiogenesis include endothelial progenitor cell (EPC) mobilization with cytokines [e.g., granulocyte colony-stimulating factor (G-CSF)] and bone marrow mononuclear cell (BMMNC) transplantation. Combined angiogenic therapies may be superior to a single angiogenic therapy for the treatment of limb ischemia. Therefore, we investigated whether the angiogenic efficacy of a combination of two angiogenic strategies is superior to either strategy alone. One day after the surgical induction of hindlimb ischemia, mice were randomized to receive either no treatment, EPC mobilization with G-CSF administration, BMMNC transplantation using a fibrin matrix, or a combination of EPC mobilization with BMMNC transplantation using a fibrin matrix. EPC mobilization with G-CSF or BMMNC transplantation using a fibrin matrix significantly increased the microvessel density compared with no treatment. Importantly, a combination of EPC mobilization with BMMNC transplantation using a fibrin matrix further increased the densities of microvessels and BrdU-positive capillaries compared to either strategy alone. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) expression was higher in the EPC mobilization with G-CSF or BMMNC transplantation group than in the no treatment group. The combination therapy of EPC mobilization with G-CSF and BMMNC transplantation resulted in more extensive expression of bFGF and VEGF than the single therapy of either EPC mobilization with G-CSF treatment or BMMNC transplantation. This study demonstrates that the combination therapy of BMMNC transplantation and EPC mobilization potentiates the angiogenic efficacy of either single therapy in mouse limb ischemia models.
authors.affiliation: Department of Chemical Engineering, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul, 133-791, Korea.
authors.forename: Oju
authors.initials: O
authors.lastname: Jeon
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Song
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Bhang
authors.forename: Cha-Yong
authors.initials: CY
authors.lastname: Choi
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D016179:Granulocyte Colony-Stimulating Factor; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000628:therapy*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000503:physiopathology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor