title: Local injections of adipose-derived mesenchymal stem cells modulate inflammation and increase angiogenesis ameliorating the dystrophic phenotype in dystrophin-deficient skeletal muscle.
abstract: The effects of adipose-derived mesenchymal stem cells (ADMSC) transplantation on degeneration, regeneration and skeletal muscle function were investigated in dystrophin-deficient mice (24-week-old). ADMSC transplantation improved muscle strength and, resistance to fatigue. An increase in fiber cross-sectional area and in the number of fibers with centralized nuclei and augment of myogenin content were observed. In ADMSC-treated muscles a decrease in muscle content of TNF-α, IL-6 and oxidative stress measured by Amplex(®) reagent were observed. The level of TGF-β1 was lowered whereas that of VEGF, IL-10 and IL-4 were increased by ADMSC treatment. An increase in markers of macrophage M1 (CD11 and F4-80) and a decrease in T lymphocyte marker (CD3) and arginase-1 were also observed in ADMSCs-treated dystrophic muscle. No change was observed in iNOS expression. Increased phosphorylation of Akt, p70S6k and 4E-BP1 was found in dystrophic muscles treated with ADMSC. These results suggest that ADMSC transplantation modulates inflammation and improves muscle tissue regeneration, ameliorating the dystrophic phenotype in dystrophin-deficient mice.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av Prof Lineu Prestes, 1524 - Prédio Biomédicas I - Cidade Universitária, Butantã, São Paulo CEP:05508-900, Brazil. chjpinheiro@gmail.com
authors.forename: Carlos Hermano da Justa
authors.initials: CH
authors.lastname: Pinheiro
authors.forename: Jean César Farias
authors.initials: JC
authors.lastname: de Queiroz
authors.forename: Lucas
authors.initials: L
authors.lastname: Guimarães-Ferreira
authors.forename: Kaio Fernando
authors.initials: KF
authors.lastname: Vitzel
authors.forename: Renato Tadeu
authors.initials: RT
authors.lastname: Nachbar
authors.forename: Luís Gustavo Oliveira
authors.initials: LG
authors.lastname: de Sousa
authors.forename: Alcione Lescano
authors.initials: AL
authors.lastname: de Souza
authors.forename: Maria Tereza
authors.initials: MT
authors.lastname: Nunes
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016189:Dystrophin / Q000172:deficiency* / Q000378:metabolism; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007267:Injections; D008264:Macrophages / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000473:pathology* / Q000628:therapy; D018008:Myogenin / Q000378:metabolism; D018919:Neovascularization, Physiologic; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016189:Dystrophin; D018836:Inflammation Mediators; D018008:Myogenin; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A