Galectin-1 induces skeletal muscle differentiation in human fetal mesenchymal stem cells and increases muscle regeneration

¹ Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, United Kingdom; Yong Lu Lin School of Medicine, National University of Singapore & National University Hospital, Singapore
² Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, United Kingdom
³ Fondazione IRCCS Ospedale Maggiore Policlinico, Department of Neurological Sciences, Stem Cell Laboratory, University of Milan, Italy
⁴ Department of Anatomy, Brighton and Sussex Medical School, Falmer, Brighton, East Sussex, United Kingdom
⁵ Muscle Cell Biology, MRC Clinical Sciences Centre and Department of Pediatrics, Imperial College London, Hammersmith Campus, London, United Kingdom

^* To whom correspondence should be addressed. E-mail: jerrychan{at}nus.edu.sg.

	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 fibres. We investigated the myogenic potential of human fetal mesenchymal stem cells (hfMSC) using a variety of stimuli. The use of 5-azacytidine or steroids did not produce skeletal muscle differentiation, while myoblast-conditioned medium resulted in only 1-2% of hfMSC undergoing muscle differentiation. However in the presence of galectin-1, 66.1±5.7% of hfMSC, but not adult bone marrow-derived MSC, assumed a muscle phenotype, forming long multinucleated fibres 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<0.001). When transplanted into regenerating murine muscle, galectin-1-exposed hfMSC formed four-fold more human muscle fibres than non-stimulated hfMSC (p=0.008), with similar results obtained in a scid/mdx dystrophic mouse model. These data suggest that hfMSC 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.