Galectin-1 Induces Skeletal Muscle Differentiation in Human Fetal Mesenchymal Stem Cells and Increases Muscle Regeneration

Authors

  • Jerry Chan MBB.Ch. MRCOG,

    Corresponding author
    1. Institute of Reproductive and Developmental Biology, Hammersmith Campus, London, United Kingdom
    • Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore & National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074. Telephone: +65-6772-4268; Fax: +65-6779-4753
    Search for more papers by this author
  • Keelin O'Donoghue,

    1. Institute of Reproductive and Developmental Biology, Hammersmith Campus, London, United Kingdom
    Search for more papers by this author
  • Manuela Gavina,

    1. Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Maggiore Policlinico, Department of Neurological Sciences, Stem Cell Laboratory, University of Milan, Italy
    Search for more papers by this author
  • Yvan Torrente,

    1. Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Maggiore Policlinico, Department of Neurological Sciences, Stem Cell Laboratory, University of Milan, Italy
    Search for more papers by this author
  • Nigel Kennea,

    1. Institute of Reproductive and Developmental Biology, Hammersmith Campus, London, United Kingdom
    Search for more papers by this author
  • Huseyin Mehmet,

    1. Institute of Reproductive and Developmental Biology, Hammersmith Campus, London, United Kingdom
    Search for more papers by this author
  • Helen Stewart,

    1. Department of Anatomy, Brighton and Sussex Medical School, Falmer, Brighton, East Sussex, United Kingdom
    Search for more papers by this author
  • Diana J. Watt,

    1. Department of Anatomy, Brighton and Sussex Medical School, Falmer, Brighton, East Sussex, United Kingdom
    Search for more papers by this author
  • Jennifer E. Morgan,

    1. Department of Paediatrics, Imperial College London, Hammersmith Campus, London, United Kingdom
    2. Muscle Cell Biology, Medical Research Council Clinical Sciences Centre, Imperial College London, London, United Kingdom
    Search for more papers by this author
  • Nicholas M. Fisk

    1. Institute of Reproductive and Developmental Biology, Hammersmith Campus, London, United Kingdom
    Search for more papers by this author

Abstract

Cell therapy for degenerative muscle diseases such as the muscular dystrophies requires a source of cells with the capacity to participate in the formation of new muscle fibers. We investigated the myogenic potential of human fetal mesenchymal stem cells (hfMSCs) using a variety of stimuli. The use of 5-azacytidine or steroids did not produce skeletal muscle differentiation, whereas myoblast-conditioned medium resulted in only 1%–2% of hfMSCs undergoing muscle differentiation. However, in the presence of galectin-1, 66.1% ± 5.7% of hfMSCs, but not adult bone marrow-derived mesenchymal stem cells, assumed a muscle phenotype, forming long, multinucleated fibers expressing both desmin and sarcomeric myosin via activation of muscle regulatory factors. Continuous exposure to galectin-1 resulted in more efficient muscle differentiation than pulsed exposure (62.3% vs. 39.1%; p < .001). When transplanted into regenerating murine muscle, galectin-1-exposed hfMSCs formed fourfold more human muscle fibers than nonstimulated hfMSCs (p = .008), with similar results obtained in a scid/mdx dystrophic mouse model. These data suggest that hfMSCs readily undergo muscle differentiation in response to galectin-1 through a stepwise progression similar to that which occurs during embryonic myogenesis. The high degree of myogenic conversion achieved by this method has relevance for the development of therapies for muscular dystrophies.

Ancillary