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

Stem Cell Rev Rep. 2012 Jun;8(2):363-74. doi: 10.1007/s12015-011-9304-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Biomarkers / metabolism
  • Cytokines / metabolism
  • Dystrophin / deficiency*
  • Dystrophin / metabolism
  • Inflammation / pathology*
  • Inflammation Mediators / metabolism
  • Injections
  • Macrophages / metabolism
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / pathology*
  • Muscular Dystrophy, Animal / pathology*
  • Muscular Dystrophy, Animal / therapy
  • Myogenin / metabolism
  • Neovascularization, Physiologic*
  • Phenotype
  • Reactive Oxygen Species / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers
  • Cytokines
  • Dystrophin
  • Inflammation Mediators
  • Myogenin
  • Reactive Oxygen Species
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A