title: Necdin enhances muscle reconstitution of dystrophic muscle by vessel-associated progenitors, by promoting cell survival and myogenic differentiation.
abstract: Improving stem cell therapy is a major goal for the treatment of muscle diseases, where physiological muscle regeneration is progressively exhausted. Vessel-associated stem cells, such as mesoangioblasts (MABs), appear to be the most promising cell type for the cell therapy for muscular dystrophies and have been shown to significantly contribute to restoration of muscle structure and function in different muscular dystrophy models. Here, we report that melanoma antigen-encoding gene (MAGE) protein necdin enhances muscle differentiation and regeneration by MABs. When necdin is constitutively overexpressed, it accelerates their differentiation and fusion in vitro and it increases their efficacy in reconstituting regenerating myofibres in the α-sarcoglycan dystrophic mouse. Moreover, necdin enhances survival when MABs are exposed to cytotoxic stimuli that mimic the inflammatory dystrophic environment. Taken together, these data demonstrate that overexpression of necdin may be a crucial tool to boost therapeutic applications of MABs in dystrophic muscle.
authors.affiliation: Department of Experimental Medicine, University of Milano-Bicocca, Monza, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pessina
authors.forename: V
authors.initials: V
authors.lastname: Conti
authors.forename: R
authors.initials: R
authors.lastname: Tonlorenzi
authors.forename: T
authors.initials: T
authors.lastname: Touvier
authors.forename: R
authors.initials: R
authors.lastname: Meneveri
authors.forename: G
authors.initials: G
authors.lastname: Cossu
authors.forename: S
authors.initials: S
authors.lastname: Brunelli
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D051379:Mice; D018345:Mice, Knockout; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049031:Sarcoglycans / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D049031:Sarcoglycans; C069766:necdin
references.citation: Cell Cycle. 2005 Mar;4(3):407-10
references.pmid: 15725724
references.citation: Curr Opin Oncol. 2011 Mar;23(2):163-9
references.pmid: 21192262
references.citation: Mol Ther. 2009 Feb;17(2):309-17
references.pmid: 19034264
references.citation: Circ Res. 2004 Jun 25;94(12):1571-8
references.pmid: 15155529
references.citation: J Cell Biol. 2006 Jul 17;174(2):231-43
references.pmid: 16831885
references.citation: J Biol Chem. 2004 Sep 24;279(39):40484-93
references.pmid: 15272023
references.citation: Nat Cell Biol. 2010 Feb;12(2):143-52
references.pmid: 20081842
references.citation: Cell Signal. 2009 Feb;21(2):228-36
references.pmid: 18983913
references.citation: J Histochem Cytochem. 2006 Nov;54(11):1177-91
references.pmid: 16899758
references.citation: J Cell Sci. 2009 Apr 15;122(Pt 8):1119-25
references.pmid: 19339547
references.citation: Mol Carcinog. 2009 Nov;48(11):975-81
references.pmid: 19626646
references.citation: J Biol Chem. 2010 Oct 1;285(40):30463-71
references.pmid: 20663865
references.citation: Science. 2003 Jul 25;301(5632):487-92
references.pmid: 12855815
references.citation: J Cell Sci. 2006 Dec 15;119(Pt 24):5114-23
references.pmid: 17158915
references.citation: Nature. 2006 Nov 30;444(7119):574-9
references.pmid: 17108972
references.citation: Nat Cell Biol. 2005 Jun;7(6):601-11
references.pmid: 15895078
references.citation: Nat Med. 2008 Sep;14(9):973-8
references.pmid: 18660817
references.citation: Oncol Rep. 2010 Sep;24(3):741-5
references.pmid: 20664982
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):264-9
references.pmid: 17182743
references.citation: J Cell Biol. 2007 Oct 8;179(1):33-40
references.pmid: 17923528
references.citation: Curr Protoc Stem Cell Biol. 2007 Dec;Chapter 2:Unit 2B.1
references.pmid: 18785178
references.citation: J Cell Sci. 2004 Sep 1;117(Pt 19):4377-88
references.pmid: 15331661
references.citation: Semin Cell Dev Biol. 2010 Oct;21(8):845-54
references.pmid: 20849971
references.citation: Semin Cell Dev Biol. 2005 Aug-Oct;16(4-5):623-31
references.pmid: 16118057
references.citation: J Cell Biol. 2007 Oct 22;179(2):305-19
references.pmid: 17954612
references.citation: Hum Mol Genet. 2000 Dec 12;9(20):3101-10
references.pmid: 11115855
references.citation: Development. 2002 Jun;129(11):2773-83
references.pmid: 12015303
references.citation: J Neurosci Res. 2002 Mar 15;67(6):705-12
references.pmid: 11891783
references.citation: Mol Ther. 2007 May;15(5):867-77
references.pmid: 17387336
references.citation: Nat Genet. 1999 Oct;23(2):199-202
references.pmid: 10508517
references.citation: J Med Genet. 1997 Nov;34(11):917-23
references.pmid: 9391886
references.citation: Nat Cell Biol. 2007 Mar;9(3):255-67
references.pmid: 17293855
references.citation: Pharmacol Res. 2008 Aug;58(2):117-21
references.pmid: 18639637