Local injections of adipose-derived mesenchymal stem cells modulate inflammation and increase angiogenesis ameliorating the dystrophic phenotype in dystrophin-deficient skeletal muscle

Carlos Hermano da Justa Pinheiro, Jean César Farias de Queiroz, Lucas Guimarães-Ferreira, Kaio Fernando Vitzel, Renato Tadeu Nachbar, Luís Gustavo Oliveira de Sousa, Alcione Lescano de Souza, Maria Tereza Nunes, Rui Curi

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)363-374
Number of pages12
JournalStem Cell Reviews and Reports
Volume8
Early online date27 Aug 2011
DOIs
Publication statusPublished - Jun 2012
Externally publishedYes

Keywords

  • Adipose Tissue/cytology
  • Biomarkers/metabolism
  • Cytokines/metabolism
  • Dystrophin/deficiency
  • Inflammation/pathology
  • Inflammation Mediators/metabolism
  • Macrophages/metabolism
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells/cytology
  • Mice
  • Muscle, Skeletal/pathology
  • Muscular Dystrophy, Animal/pathology
  • Myogenin/metabolism
  • Neovascularization, Physiologic

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