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Human Multipotent Mesenchymal Stromal Cells from Distinct Sources Show Different In Vivo Potential to Differentiate into Muscle Cells When Injected in Dystrophic Mice

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Abstract

Limb-girdle muscular dystrophies are a heterogeneous group of disorders characterized by progressive degeneration of skeletal muscle caused by the absence or deficiency of muscle proteins. The murine model of Limb-Girdle Muscular Dystrophy 2B, the SJL mice, carries a deletion in the dysferlin gene. Functionally, this mouse model shows discrete muscle weakness, starting at the age of 4–6 weeks. The possibility to restore the expression of the defective protein and improve muscular performance by cell therapy is a promising approach for the future treatment of progressive muscular dystrophies (PMD). We and others have recently shown that human adipose multipotent mesenchymal stromal cells (hASCs) can differentiate into skeletal muscle when in contact with dystrophic muscle cells in vitro and in vivo. Umbilical cord tissue and adipose tissue are known rich sources of multipotent mesenchymal stromal cells (MSCs), widely used for cell-based therapy studies. The main objective of the present study is to evaluate if MSCs from these two different sources have the same potential to reach and differentiate in muscle cells in vivo or if this capability is influenced by the niche from where they were obtained. In order to address this question we injected human derived umbilical cord tissue MSCs (hUCT MSCs) into the caudal vein of SJL mice with the same protocol previously used for hASCs; we evaluated the ability of these cells to engraft into recipient dystrophic muscle after systemic delivery, to express human muscle proteins in the dystrophic host and their effect in functional performance. These results are of great interest for future therapeutic application.

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Acknowledgments

We gratefully acknowledge our colleagues Marcos Valadares, Tatiana Jazedje, Amanda Assoni, Mayra Pelatti, Juliana Gomes, Gabriela Polster, Camila Almeida, Agnes Nishimura, Natale Cavaçana, Miguel Mitne-Neto, Monize Lazar, Constancia Urbani, David Schlesinger, Daniela Bueno, Roberto Fanganiello, Antonia M P Cerqueira, Marta Canovas, Paula Onofre and Dr. Maria Rita Passos-Bueno for helpful suggestions. We thank Dr. Glenn Morris from the Center for Inherited Neuromuscular Disease (CIND), RJAH Orthopaedic Hospital, Oswestry, Shropshire, UK for providing anti-human dystrophin antibody.

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Authors and Affiliations

  1. Human Genome Research Center, Institute of Biosciences, University of São Paulo, Rua do Matão, n.106—Cidade Universitária, São Paulo, SP, CEP: 05508-090, Brazil

    N. M. Vieira, E. Zucconi, C. R. Bueno Jr., M. Secco, M. Vainzof & M. Zatz

  2. Biotechnology Department, National Nuclear Energy Commission-IPEN-CNEN, São Paulo, Brazil

    M. F. Suzuki & P. Bartolini

Authors
  1. N. M. Vieira
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  2. E. Zucconi
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  3. C. R. Bueno Jr.
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  4. M. Secco
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  5. M. F. Suzuki
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  6. P. Bartolini
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  7. M. Vainzof
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  8. M. Zatz
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Corresponding author

Correspondence to M. Zatz.

Additional information

N. M. Vieira and E. Zucconi contributed equally for this work.

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Vieira, N.M., Zucconi, E., Bueno, C.R. et al. Human Multipotent Mesenchymal Stromal Cells from Distinct Sources Show Different In Vivo Potential to Differentiate into Muscle Cells When Injected in Dystrophic Mice. Stem Cell Rev and Rep 6, 560–566 (2010). https://doi.org/10.1007/s12015-010-9187-5

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