Tratamento ex-vivo com óxido nítrico melhora os resultados do tratamento da distrofia muscular com mesangioblastos em camundongos
Itália – esta pesquisa é do mesmo grupo que recentemente demonstrou em cães bons resultados com o uso de mesangioblastos para tratamento da distrofia muscular. Neste estudo em camundongos os mesangioblastos foram tratados previamente, antes da injeção, com doadores de óxido nítrico. Estas células tratadas foram mais eficientes para tratamento da distrofia muscular do que as células não tratadas. O resumo em inglês desta pesquisa pode ser lido abaixo:
(IN PRESS: Journal of Cell Science 2006; 119: 5114-5123) 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 Cossuand Emilio Clementi – Italy
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 -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 -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.
