Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability
Galvez, Beatriz G × Sampaolesi, Maurilio Brunelli, Silvia Covarello, Diego Gavina, Manuela Rossi, Barbara Costantin, Gabriela Torrente, Yvan Cossu, Giulio #
Journal of Cell Biology vol:174 issue:2 pages:231-243
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 (> 50%) followed by reconstitution of > 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.