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 alpha4 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 alpha4 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.

Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability.

ROSSI, Barbara;CONSTANTIN, Gabriela;
2006

Abstract

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 alpha4 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 alpha4 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.
cell migration; inflammation; integrins; selectins; cytokines
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/227616
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