title: Impact of angiogenic therapy in the treatment of critical lower limb ischemia in an animal model.
abstract: Angiogenic therapies for critical limb ischemia were tested in a mouse model. The mice were anesthetized and their femoral arteries were ligated. The animals were treated with bone marrow mononuclear cells (BMMCs) alone, BMMCs combined with plasmid vector encoding granulocyte macrophage colony-stimulating factor (GM-CSF), received no treatment, or no intervention (controls). The degree of ischemia was monitored for 4 weeks using a visual scale. Muscle atrophy and strength were assessed at 4 weeks postoperatively; the mice were then killed. In treated animals, total necrosis of the limb was not found, the weight of the gastrocnemius and quadriceps muscles was significantly higher, functional ability and tissue regeneration were significantly increased, and muscle impairment and adipocyte presence were significantly reduced compared with untreated animals. At inducing angiogenesis, the BMMCs alone was more effective than BMMCs combined with plasmid vector encoding GM-CSF. Treated animals showed increased angiogenesis compared with ischemic untreated ones.
authors.affiliation: Department of Specialized and General Surgery, Fluminense Federal University (UFF), Niterói, Rio de Janeiro, Brazil.
authors.forename: Paulo Eduardo Ocke
authors.initials: PE
authors.lastname: Reis
authors.forename: Leonardo Pinto
authors.initials: LP
authors.lastname: de Carvalho
authors.forename: Eduardo
authors.initials: E
authors.lastname: Yasumura
authors.forename: Flavia Helena
authors.initials: FH
authors.lastname: da Silva
authors.forename: Bianca Cristina
authors.initials: BC
authors.lastname: Garcia
authors.forename: Abram
authors.initials: A
authors.lastname: Beutel
authors.forename: Chester Bittencourt
authors.initials: CB
authors.lastname: Sacramento
authors.forename: José Carlos Costa
authors.initials: JC
authors.lastname: Baptista-Silva
authors.forename: Ruy Ribeiro
authors.initials: RR
authors.lastname: de Campos
authors.forename: Christina Maeda
authors.initials: CM
authors.lastname: Takiya
authors.forename: Radovan
authors.initials: R
authors.lastname: Borojevic
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Han
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D016638:Critical Illness; D004195:Disease Models, Animal; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006614:Hindlimb; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053580:Muscle Strength; D009133:Muscular Atrophy / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009336:Necrosis; D018919:Neovascularization, Physiologic; D052097:Quadriceps Muscle / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014162:Transfection
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: angiogenesis-inducing agents; cell therapy; gene therapy; ischemia; lower extremity