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

Beatriz G. Galvez, Maurilio Sampaolesi, Silvia Brunelli, Diego Covarello, Manuela Gavina, Barbara Rossi, Gabriela Costantin, Yvan Torrente, Giulio Cossu

Research output: Contribution to journalArticle

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 (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.

Original languageEnglish
Pages (from-to)231-243
Number of pages13
JournalJournal of Cell Biology
Volume174
Issue number2
DOIs
Publication statusPublished - Jul 17 2006

ASJC Scopus subject areas

  • Cell Biology

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    Galvez, B. G., Sampaolesi, M., Brunelli, S., Covarello, D., Gavina, M., Rossi, B., Costantin, G., Torrente, Y., & Cossu, G. (2006). Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability. Journal of Cell Biology, 174(2), 231-243. https://doi.org/10.1083/jcb.200512085