Efficient delivery of cells to target tissues is a major problem in cell therapy. We report that enhancing delivery of mesoangioblasts leads to a complete reconstitution of downstream skeletal muscles in a mouse model of severe muscular dystrophy (α-sarcoglycan ko). Mesoangioblasts, vessel-associated stem cells, were exposed to several cytokines, among which stromal- derived factor (SDF) 1 or tumor necrosis factor (TNF) α were the most potent in enhancing transmigration in vitro and migration into dystrophic muscle in vivo. Transient expression of α4 integrins or L-selectin also increased several fold migration both in vitro and in vivo. Therefore, combined pretreatment with SDF-1 or TNF-α and expression of α4 integrin leads to massive colonization (>50%) followed by reconstitution of >80% of α-sarcoglycan–expressing fibers, with a fivefold increase in efficiency in comparison with control cells. This study defines the requirements for efficient engraftment of mesoangioblasts and offers a new potent tool to optimize future cell therapy protocols for muscular dystrophies.
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17 July 2006
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July 10 2006
Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability
Beatriz G. Galvez,
Beatriz G. Galvez
1Stem Cell Research Institute, San Raffaele Hospital, 20132 Milan, Italy
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Maurilio Sampaolesi,
Maurilio Sampaolesi
1Stem Cell Research Institute, San Raffaele Hospital, 20132 Milan, Italy
2Department of Experimental Medicine, Human Anatomy Institute, University of Pavia, 27100 Pavia, Italy
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Silvia Brunelli,
Silvia Brunelli
1Stem Cell Research Institute, San Raffaele Hospital, 20132 Milan, Italy
3Department of Experimental, Environmental Medicine, and Medical Biotechnology, University of Milano-Bicocca, 20126 Milan, Italy
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Diego Covarello,
Diego Covarello
1Stem Cell Research Institute, San Raffaele Hospital, 20132 Milan, Italy
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Manuela Gavina,
Manuela Gavina
4Stem Cell Laboratory, Department of Neurological Science,
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Barbara Rossi,
Barbara Rossi
6Department of Pathology, Division of General Pathology, University of Verona, 37129 Verona, Italy
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Gabriela Constantin,
Gabriela Constantin
6Department of Pathology, Division of General Pathology, University of Verona, 37129 Verona, Italy
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Yvan Torrente,
Yvan Torrente
4Stem Cell Laboratory, Department of Neurological Science,
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Giulio Cossu
Giulio Cossu
1Stem Cell Research Institute, San Raffaele Hospital, 20132 Milan, Italy
5Department of Biology, University of Milan, 20122 Milan, Italy
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Beatriz G. Galvez
1Stem Cell Research Institute, San Raffaele Hospital, 20132 Milan, Italy
Maurilio Sampaolesi
1Stem Cell Research Institute, San Raffaele Hospital, 20132 Milan, Italy
2Department of Experimental Medicine, Human Anatomy Institute, University of Pavia, 27100 Pavia, Italy
Silvia Brunelli
1Stem Cell Research Institute, San Raffaele Hospital, 20132 Milan, Italy
3Department of Experimental, Environmental Medicine, and Medical Biotechnology, University of Milano-Bicocca, 20126 Milan, Italy
Diego Covarello
1Stem Cell Research Institute, San Raffaele Hospital, 20132 Milan, Italy
Manuela Gavina
4Stem Cell Laboratory, Department of Neurological Science,
Barbara Rossi
6Department of Pathology, Division of General Pathology, University of Verona, 37129 Verona, Italy
Gabriela Constantin
6Department of Pathology, Division of General Pathology, University of Verona, 37129 Verona, Italy
Yvan Torrente
4Stem Cell Laboratory, Department of Neurological Science,
Giulio Cossu
1Stem Cell Research Institute, San Raffaele Hospital, 20132 Milan, Italy
5Department of Biology, University of Milan, 20122 Milan, Italy
Correspondence to Giulio Cossu: [email protected]
Abbreviations used in this paper: ctx, cardiotoxin; HMGB, high mobility group box; ICAM, intercellular adhesion molecule; IL, interleukin; mdx, X chromosome–linked muscular dystrophy; MMP, metalloproteinase; PECAM, platelet endothelial cell adhesion molecule; SDF, stromal-derived factor; SG, sarcoglycan; VCAM, vascular cell adhesion molecule; WT, wild-type.
Received:
December 15 2005
Accepted:
June 16 2006
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2006
J Cell Biol (2006) 174 (2): 231–243.
Article history
Received:
December 15 2005
Accepted:
June 16 2006
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Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability
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Correction: Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration abilit
This article has been corrected
Correction: Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability
Citation
Beatriz G. Galvez, Maurilio Sampaolesi, Silvia Brunelli, Diego Covarello, Manuela Gavina, Barbara Rossi, Gabriela Constantin, Yvan Torrente, Giulio Cossu; Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability . J Cell Biol 17 July 2006; 174 (2): 231–243. doi: https://doi.org/10.1083/jcb.200512085
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