Ex vivo treatment with nitric oxide increases mesoangioblast therapeutic efficacy in muscular dystrophy

Clara Sciorati, Beatriz G. Galvez, Silvia Brunelli, Enrico Tagliafico, Stefano Ferrari, Giulio Cossu, Emilio Clementi

Research output: Contribution to journalArticlepeer-review

Abstract

Muscular dystrophies are characterized by primary wasting of skeletal muscle for which no satisfactory therapy is available. Studies in animal models have shown that stem cell-based therapies may improve the outcome of the disease, and that mesoangioblasts are promising stem cells in this respect. The efficacy of mesoangioblasts in yielding extensive muscle repair is, however, still limited. We found that mesoangioblasts; treated with nitric oxide (NO) donors and injected intra-arterially in α-sarcoglycan-null dystrophic mice have a significantly enhanced ability to migrate to dystrophic muscles, to resist their apoptogenic environment and engraft into them, yielding a significant recovery of α-sarcolgycan expression. In vitro NO-treated mesoangioblasts displayed an enhanced chemotactic response to myotubes, cytokines and growth factors generated by the dystrophic muscle. In addition, they displayed an increased ability to fuse with myotubes and differentiating myoblasts and to survive when exposed to cytotoxic stimuli similar to those present in the dystrophic muscle. All the effects of NO were cyclic GMP-dependent since they were mimicked by treatment with the membrane permeant cyclic-GMP analogue 8-bromo-cGMP and prevented by inhibiting guanylate cyclase. We conclude that NO donors exert multiple beneficial effects on mesoangioblasts that may be used to increase their efficacy in cell therapy of muscular dystrophies.

Original languageEnglish
Pages (from-to)5114-5123
Number of pages10
JournalJournal of Cell Science
Volume119
Issue number24
DOIs
Publication statusPublished - Dec 15 2006

Keywords

  • Apoptosis
  • Cyclic GMP
  • Differentiation
  • Muscular dystrophy
  • Nitric oxide
  • Stem cells

ASJC Scopus subject areas

  • Cell Biology

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