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Stem Cell Reviews and Reports

, Volume 9, Issue 1, pp 93–109 | Cite as

Systemic Delivery of Human Mesenchymal Stromal Cells Combined with IGF-1 Enhances Muscle Functional Recovery in LAMA2 dy/2j Dystrophic Mice

  • Mariane Secco
  • Carlos BuenoJr
  • Natassia M. Vieira
  • Camila Almeida
  • Mayra Pelatti
  • Eder Zucconi
  • Paolo Bartolini
  • Mariz Vainzof
  • Elen H. Miyabara
  • Oswaldo K. Okamoto
  • Mayana Zatz
Article

Abstract

The combination of cell therapy with growth factors could be a useful approach to treat progressive muscular dystrophies. Here, we demonstrate, for the first time, that IGF-1 considerably enhances the myogenesis of human umbilical cord (UC) mesenchymal stromal cells (MSCs) in vitro and that IGF-1 enhances interaction and restoration of dystrophin expression in co-cultures of MSCs and muscle cells from Duchenne patients. In vivo studies showed that human MSCs were able to reach the skeletal muscle of LAMA2 dy/2j dystrophic mice, through systemic delivery, without immunosuppression. Moreover, we showed, for the first time, that IGF-1 injected systemically together with MSCs markedly reduced muscle inflammation and fibrosis, and significantly improved muscle strength in dystrophic mice. Our results suggest that a combined treatment with IGF-1 and MSCs enhances efficiency of muscle repair and, therefore, should be further considered as a potential therapeutic approach in muscular dystrophies.

Keywords

Muscular dystrophies IGF-1 Mesenchymal stromal cells 

Notes

Acknowledgments

Members from University Hospital, Constancia Urbani, Marcos Valadares, Tatiana Jazedje, Estela Cruvinel, Carla Freitas, Juliana Gomes, Amanda Assoni, Gabriela Polster, Heloisa Caetano, Tabata Leal, Maria Neide Mascarenhas, Miriam Suzuki, Paula Onofre, Marta Canovas, Fernando Luis Molina and Maria Rita Passos-Bueno are gratefully acknowledged for support and for helpful suggestions. We would like to thank Dr. Glenn Morris from the Center for Inherited Neuromuscular Disease (CIND) - UK for providing anti-human dystrophin antibody. This work was supported with grants of CEPID-FAPESP (Centro de Pesquisa, Inovação e Difusão-Fundação de Amparo a Pesquisa do Estado de São Paulo), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), INCT (Instituto Nacional de Ciência e Tecnologia). The authors indicate no potential conflicts of interest.

Disclosures

The authors indicate no potential conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Mariane Secco
    • 1
  • Carlos BuenoJr
    • 1
  • Natassia M. Vieira
    • 1
  • Camila Almeida
    • 1
  • Mayra Pelatti
    • 1
  • Eder Zucconi
    • 1
  • Paolo Bartolini
    • 2
  • Mariz Vainzof
    • 1
  • Elen H. Miyabara
    • 3
  • Oswaldo K. Okamoto
    • 1
  • Mayana Zatz
    • 1
  1. 1.Human Genome Research Center, Department of Genetic and Evolutionary BiologyInstitute of BiosciencesSão PauloBrazil
  2. 2.Department of BiotechnologyNational Nuclear Energy Commission-IPEN-CNENSão PauloBrazil
  3. 3.Department of AnatomyInstitute of Biomedical Sciences, University of São PauloSão PauloBrazil

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