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Human Adipose Tissue Derived Pericytes Increase Life Span in Utrn tm1Ked Dmd mdx/J Mice

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Abstract

Duchenne muscular dystrophy (DMD) is still an untreatable lethal X-linked disorder, which affects 1 in 3500 male births. It is caused by the absence of muscle dystrophin due to mutations in the dystrophin gene. The potential regenerative capacity as well as immune privileged properties of mesenchymal Stem Cells (MSC) has been under investigation for many years in an attempt to treat DMD. One of the questions to be addressed is whether stem cells from distinct sources have comparable clinical effects when injected in murine or canine muscular dystrophy animal models. Many studies comparing different stem cells from various sources were reported but these cells were obtained from different donors and thus with different genetic backgrounds. Here we investigated whether human pericytes obtained from 4 different tissues (muscle, adipose tissue, fallopian tube and endometrium) from the same donor have a similar clinical impact when injected in double mutant Utrn tm1Ked Dmd mdx/J mice, a clinically relevant model for DMD. After a weekly regimen of intraperitoneal injections of 106 cells per 8 weeks we evaluated the motor ability as well as the life span of the treated mice as compared to controls. Our experiment showed that only adipose tissue derived pericytes are able to increase significantly (39 days on average) the life span of affected mice. Microarray analysis showed an inhibition of the interferon pathway by adipose derived pericytes. Our results suggest that the clinical benefit associated with intraperitoneal injections of these adult stem cells is related to immune modulation rather than tissue regeneration.

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Acknowledgments

We would like to thank Eder Zucconi, Mariane Secco, Tatiana Jazedje, Natássia Vieira, Natale Cavaçana, Naila Lourenço, Michel Naslavsky, Melinda Becari, Bárbara de Bélis, Lúcia Inês and Thiago Olávio for their helpful suggestions throughout the project. Constância Gotto, Vanessa Sato and Wagner Falciano for administrative support. Marta Canovas for her help with the tissue sections and Neide Mascarenhas and co-workers from IPEN for the collaboration regarding animal care. We gratefully acknowledge Prof. Oswaldo Keith Okamoto for the critical reading of this MS. This work was supported by CEPID/FAPESP, INCT and CNPq.

Conflict of Interest

We declare no conflict of interest.

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Authors and Affiliations

  1. Human Genome and stem-cell Center, Institute of Biosciences, University of São Paulo, Rua do Matāo 106, São Paulo, CEP 05508-030, Brazil

    M. C. Valadares, J. P. Gomes, G. Castello, A. Assoni, M. Pellati, C. Bueno, M. Vainzof & M. Zatz

  2. UCLA and Orthopaedic Hospital, Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, CA, USA

    M. Corselli & B. Péault

  3. Center for Diagnosis and Investigation of Malignant Hyperthermia, Department of Surgery, Federal University of São Paulo, São Paulo, Brazil

    H. Silva

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

    P. Bartolini

  5. Division of Obstetrics and Gynecology, Hospital University, University of São Paulo, São Paulo, Brazil

    P. F. Margarido

  6. Gynecology Division, Department of Obstetrics and Gynecology, Laboratory of Structural and Molecular Gynecology (LIM-58), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    E. Baracat

Authors
  1. M. C. Valadares
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  2. J. P. Gomes
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  3. G. Castello
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  5. M. Pellati
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  6. C. Bueno
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  7. M. Corselli
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  8. H. Silva
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  9. P. Bartolini
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  12. E. Baracat
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  14. M. Zatz
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Correspondence to M. Zatz.

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Valadares, M.C., Gomes, J.P., Castello, G. et al. Human Adipose Tissue Derived Pericytes Increase Life Span in Utrn tm1Ked Dmd mdx/J Mice. Stem Cell Rev and Rep 10, 830–840 (2014). https://doi.org/10.1007/s12015-014-9537-9

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  • DOI: https://doi.org/10.1007/s12015-014-9537-9

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