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 ((alpha)-sarcoglycan ko). Mesoangioblasts, vessel-associated stem cells, were exposed to several cytokines, among which stromal-derived factor (SDF) 1 or tumor necrosis factor (TNF) (alpha) were the most potent in enhancing transmigration in vitro and migration into dystrophic muscle in vivo. Transient expression of (alpha)4 integrins or L-selectin also increased several fold migration both in vitro and in vivo. Therefore, combined pretreatment with SDF-1 or TNF-(alpha) and expression of (alpha)4 integrin leads to massive colonization (&rt;50%) followed by reconstitution of &rt;80% of (alpha)-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. (copyright) The Rockefeller University Press.
Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability / B.G. Galvez, M. Sampaolesi, S. Brunelli, D. Covarello, M. Gavina, B. Rossi, G. Costantin, Y. Torrente, G. Cossu. - In: THE JOURNAL OF CELL BIOLOGY. - ISSN 0021-9525. - 174:2(2006 Jul), pp. 231-243.
|Titolo:||Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability|
TORRENTE, YVAN (Penultimo)
COSSU, GIULIO (Ultimo)
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
Settore BIO/17 - Istologia
|Data di pubblicazione:||lug-2006|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1083/jcb.200512085|
|Appare nelle tipologie:||01 - Articolo su periodico|