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Abstract

Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP+ cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers only in differentiated myotubes, which they form spontaneously with high efficiency. When transplanted into severe combined immune deficient–X-linked, mouse muscular dystrophy (scid–mdx) mice, pericyte-derived cells colonize host muscle and generate numerous fibres expressing human dystrophin. Similar cells isolated from Duchenne patients, and engineered to express human mini-dystrophin, also give rise to many dystrophin-positive fibres in vivo. These data show that myogenic precursors, distinct from satellite cells, are associated with microvascular walls in the human skeletal muscle, may represent a correlate of embryonic 'mesoangioblasts' present after birth and may be a promising candidate for future cell-therapy protocols in patients.

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Acknowledgements

This work was supported by grants from Muscular Dystrophy Association (MDA), Telethon, Association Française contra les Myopathies (AFM), Parent Project Onlus, Cassadi Risparmio Province Lombarde (CARIPLO), Associazione Italiana ricerca sul Cancro (AIRC), EC 'Eurostemcell', 'Cellsintoorgan', MyoAmp and 'Genostem', and the Italian Ministries of Health and Research. We thank G. Arrigo for help with karyotype analysis and A. Palini for help with FACS analysis. We also thank E. Dejana for advice and for reading the manuscript.

Author information

Author notes

    • Arianna Dellavalle
    •  & Maurilio Sampaolesi

    These authors contributed equally to this work.

Affiliations

  1. Stem Cell Research Institute, San Raffaele Scientific Institute, 58 Via Olgettina, 20132 Milan, Italy.

    • Arianna Dellavalle
    • , Maurilio Sampaolesi
    • , Rossana Tonlorenzi1
    • , Laura Perani
    • , Anna Innocenzi
    • , Beatriz G. Galvez
    • , Graziella Messina
    • , Giuseppe Peretti
    •  & Giulio Cossu
  2. Department of Experimental Medicine, University of Pavia, 6 Via Forlanini, 27100 Pavia, Italy.

    • Maurilio Sampaolesi
  3. Department of Biomedical Sciences, University of Modena and Reggio Emilia, 287 Via Campi, 41100 Modena, Italy.

    • Enrico Tagliafico
    •  & Stefano Ferrari
  4. Institute of Cell Biology and Tissue Engineering, San Raffaele Biomedical Science Park, 100/2 Via Castel Romano, 00128 Rome, Italy.

    • Benedetto Sacchetti
    • , Paolo Bianco
    •  & Giulio Cossu
  5. Department of Cellular and Developmental Biology, University of Rome La Sapienza, 5 Piazza Aldo Moro, 00161 Rome, Italy.

    • Graziella Messina
  6. Department of Neurology, Catholic University, 8 Largo A. Gemelli, 00168 Rome, Italy.

    • Roberta Morosetti
  7. Department of Neurology, University of Washington, 1959 N.E. Pacific Street, Seattle, WA 98195-7720. USA.

    • Sheng Li
    •  & Jeffrey S. Chamberlain
  8. Department of Neurological Science, Ospedale Maggiore Policlinico, University of Milan, 35 Via Francesco Sforza, 20122 Milan, Italy.

    • Marzia Belicchi
    •  & Yvan Torrente
  9. UT Southwestern Medical Center, Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9039, USA.

    • Woodring E. Wright
  10. Department of Experimental Pathology, University of Rome La Sapienza, 324 Via Regina Elena, 00161 Rome, Italy.

    • Paolo Bianco
  11. Department of Biology, University of Milan, 26 Via Celoria, 20130 Milan, Italy.

    • Giulio Cossu

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Contributions

A.D. and M.S. coordinated the work and performed the in vivo transplantation and functional tests. R.T. performed the cell cultures with help from G.M. and R.M. E.T. and S.F. conducted the microarray analysis. B.S. and A.D. did the FACS work. L.P. performed the PCR and western blot analysis. A.I. and M.B. did the immunocytochemistry. B.G.G. performed the homing experiment. S.L. and J.S.C. provided the viral vectors and advice. G.P. and Y.T. provided the biological samples. W.E.W. performed the telomerase work, provide advice and revised the manuscript. P.B. and G.C. coordinated the whole project and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Paolo Bianco or Giulio Cossu.

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    Supplementary Information

    Supplementary Figures S1, S2, S3 and Supplementary Methods

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DOI

https://doi.org/10.1038/ncb1542

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