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Local Injections of Adipose-Derived Mesenchymal Stem Cells Modulate Inflammation and Increase Angiogenesis Ameliorating the Dystrophic Phenotype in Dystrophin-Deficient Skeletal Muscle

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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.

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Acknowledgements

C.H.J Pinheiro was scholar fellowship of São Paulo Research Foundation—FAPESP [2008/54693-9]. The authors thank Emilia Ribeiro, J.R. de Mendonça, Dr. Tatiana C. Alba Loureiro and Adhemar Pettri Filho for constant assistance. This work was also supported by the National Council for Scientific and Technological Development (CNPq) [573557/2008-0].

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Authors and Affiliations

  1. 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/SP, CEP:05508-900, Brazil

    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-Jr, Maria Tereza Nunes & Rui Curi

  2. National Network of Cellular Therapy (RNTC), Butantã, Brazil

    Carlos Hermano da Justa Pinheiro, Kaio Fernando Vitzel, Renato Tadeu Nachbar & Rui Curi

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  1. Carlos Hermano da Justa Pinheiro
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  2. Jean César Farias de Queiroz
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Correspondence to Carlos Hermano da Justa Pinheiro.

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da Justa Pinheiro, C.H., de Queiroz, J.C.F., Guimarães-Ferreira, L. et al. 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 and Rep 8, 363–374 (2012). https://doi.org/10.1007/s12015-011-9304-0

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