Journal
STEM CELL REVIEWS AND REPORTS
Volume 8, Issue 2, Pages 363-374Publisher
SPRINGER
DOI: 10.1007/s12015-011-9304-0
Keywords
Muscular dystrophy; Mesenchymal stem cells; Stem cell transplantation; Inflammation; Cytokines; Angiogenesis; Skeletal muscle function
Funding
- Sao Paulo Research Foundation-FAPESP [2008/54693-9]
- National Council for Scientific and Technological Development (CNPq) [573557/2008-0]
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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-alpha, IL-6 and oxidative stress measured by Amplex(A (R)) reagent were observed. The level of TGF-beta 1 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.
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