Isolation of adult muscle stem cells for skeletal muscle repair

Researchers from the MRC Clinical Sciences Centre and Imperial College London, in collaboration with scientists from the Pasteur Institute and CNRS Paris, have succeeded in using flow cytometry to isolate pure preparations of muscle stem cells from skeletal muscles of adult mice (Science Express, 1st September). These cells correspond to satellite cells, a small population of precursor cells that are found on the outside of muscle fibres and are responsible for post-natal growth and repair of skeletal muscles. The researchers used a combination of cellular markers to purify these cells. The selection procedure they describe results in cells that can both repair skeletal muscle and give rise to new satellite cells.

Previous studies employed muscle precursor cells that corresponded to the progeny of muscle satellite cells, obtained after activation and proliferation in culture. The purification procedure described in this study allows the direct isolation of large numbers of quiescent satellite cells from muscle tissue, removing the need for expansion in tissue culture.

The results reported now show that freshly-purified satellite cells are markedly more efficient than cultured cell populations in contributing to muscle regeneration. When tested for their ability to repair dystrophic mouse muscle, it was found that 20,000 purified stem/satellite cells were as efficient as 1,000,000 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 expand and colonize grafted muscle compared to cultured cells, which differentiate too rapidly. This is reminiscent of hematopoietic stem cells, which also begin to differentiate and 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 myopathic skeletal muscles.

This work, to be published in Science Express on the 1st of September, complements work conducted by the same MRC/ Imperial College team that was published in Cell in July, which conclusively demonstrated that satellite cells undergo self-renewal and constitute a population of tissue-specific stem cells resident within adult skeletal muscle.

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, september 1st Didier Montarras1*, Jennifer Morgan2,3, Charlotte Collins3, Frédéric Relaix1, Stéphane Zaffran1, Ana Cumano4, Terence Partridge3, Margaret Buckingham 1*
1C.N.R.S. URA 2578, Department of Developmental Biology, Pasteur Institute, 75724 Paris Cedex 15, France. 2Department of Paediatrics, Imperial College London, The Dubowitz Neuromuscular Centre, Hammersmith Hospital, Du Cane Road, London W12 ONN. 3Muscle Cell Biology Group, MRC Clinical Sciences Centre, Imperial College, Du Cane Road, London W12 ONN. 4Unité du Développement des Lymphocytes, U 668 I.N.S.E.R.M. Pasteur Institute, 75724 Paris Cedex 15, France.