Isolation of adult muscle stem cells for skeletal muscle repair

Researchers from the Institut Pasteur and the CNRS have succeeded in isolating muscle stem cells displaying a high potential for muscle repair. These cells, which correspond to satellite cells, were, until now, inaccessible in their native state. Twenty thousand muscle stem/satellite cells were sufficient to promote significant muscle repair in mice, whereas one million cultured muscle precursor cells were required in previous assays. This work, published on September 1st in Science provides important new insights into adult muscle stem cells and sheds new light on the potential of such cells for the cell therapy of muscular defects.

 

 

Press release
Paris, september 2, 2005

 

 

Stem cells represent a great hope for the future of cell therapy. Following the paradigm of haematopoietic stem cells, which reconstitute blood cells, many attempts have been undertaken to isolate cells able to efficiently repair adult differentiated tissues such as skeletal muscle. The purification procedure described today gives direct access to stem/satellite cells which can both repair and contribute to the progenitor cell population of damaged muscles. In the past, the difficulty of isolating pure populations of satellite cells in sufficient number has precluded their use in cell based tissue repair assays. Previous assays have, therefore, employed muscle precursor cells that correspond to the progeny of muscle satellite cells, obtained after activation and proliferation in culture.

The results reported by Didier Montarras and colleagues, in the Unité de Génétique Moléculaire du Développement (Institut Pasteur/CNRS) directed by Margaret Buckingham, show that purified stem/satellite cells are markedly more efficient than cultured muscle precursor cells in contributing to muscle repair. Twenty thousand purified stem/satellite cells, when grafted in dystrophic mouse muscles, were as efficient as one million cultured cells in muscle fibre repair. The researchers explain that the higher regenerative capacity of freshly isolated muscle stem cells reflects a better capacity to colonize grafted muscle compared to cultured cells, which differentiate too rapidly. A similar situation is encountered with haematopoietic stem cells, which begin to differentiate and to lose their tissue reconstitution capacity when cultured.

The muscle stem/satellite cell population described in this work is clearly the major contributor to muscle regeneration and a potential therapeutic agent. This work paves the way for the isolation of human stem/satellite cells and their therapeutic use for the repair of degenerated skeletal muscles.

This work, published in Science on the 1st of September is the result of a collaboration between two French teams and one English team.
This research has been financed jointly by the Institut Pasteur, the CNRS (Centre National de la Recherche Scientifique), the AFM, (Association Française contre les Myopathies), the Integrated project EuroStemCell (European Research Consortium on stem cells), the MRC (Medical Research Council) and the Muscular Dystrophy Campaign.

Sources

" Direct isolation of satellite cells for skeletal muscle regeneration" Science, 1 septembre 2005.
Didier Montarras (1), Jennifer Morgan (2,3), Charlotte Collins (3), Frédéric Relaix (1), Stéphane Zaffran (1), Ana Cumano (4), Terence Partridge (3), Margaret Buckingham (1))

1. Unité de Génétique moléculaire du développement, CNRS-Institut Pasteur
2. Département de Pédiatrie, Imperial College London, The Dubowitz Neuromuscular Centre, Hammersmith Hospital, Du Cane Road, London
3. Muscle Cell Biology Group, MRC Clinical Sciences Centre, Imperial College, Du Cane Road, London
4. Unité du Développement des Lymphocytes, U 668 I.N.S.E.R.M. Institut Pasteur

(1) " A Pax3/Pax7 – dependent population of skeletal muscle progenitor cells" Nature, 7 juin 2005.
Frédéric Relaix (1), Didier Rocancourt (1), Ahmed Mansourt (2), Margaret Buckingham (1),

1. Unité de Génétique moléculaire du développement, CNRS-Institut Pasteur
2. Max-Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Gottingen, Germany

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01 44 38 91 30 -  bbaron@pasteur.fr

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Martine Hasler
01 44 96 46 06 - martine.hasler@cnrs-dir.fr

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