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

Chan, Jerry, O’Donoghue, Keelin, Gavina, Manuela, Torrente, Yvan, Kennea, Nigel, Mehmet, Huseyin, Stewart, Helen, Watt, Diana J., Morgan, Jennifer E. and Fisk, Nicholas M. (2006) Galectin-1 induces skeletal muscle differentiation in human fetal mesenchymal stem cells and increases muscle regeneration. Stem Cells, 24 8: 1879-1891. doi:10.1634/stemcells.2005-0564


Author Chan, Jerry
O’Donoghue, Keelin
Gavina, Manuela
Torrente, Yvan
Kennea, Nigel
Mehmet, Huseyin
Stewart, Helen
Watt, Diana J.
Morgan, Jennifer E.
Fisk, Nicholas M.
Title Galectin-1 induces skeletal muscle differentiation in human fetal mesenchymal stem cells and increases muscle regeneration
Journal name Stem Cells   Check publisher's open access policy
ISSN 1066-5099
1549-4918
Publication date 2006-08-01
Year available 2006
Sub-type Article (original research)
DOI 10.1634/stemcells.2005-0564
Open Access Status
Volume 24
Issue 8
Start page 1879
End page 1891
Total pages 13
Editor Donald G. Phinney
Miodrag Stojković
Place of publication Durham, NC, U.S.A
Publisher Wiley-Blackwell and AlphaMed Press
Language eng
Subject 111401 Foetal Development and Medicine
111402 Obstetrics and Gynaecology
1114 Paediatrics and Reproductive Medicine
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.
Formatted 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.
Copyright © 2010 AlphaMed Press.

Keyword Mesenchymal stem cells
scid/mdx
Muscle differentiation
Galectin-1
Fetal stem cells
Fetal
Myogenesis
Q-Index Code C1
Institutional Status Non-UQ
Additional Notes First published online in STEM CELLS EXPRESS May 4, 2006.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Sat, 21 Mar 2009, 01:35:16 EST by Mary-Anne Marrington on behalf of Faculty Of Health Sciences