Bisperoxovanadium, a phospho-tyrosine phosphatase inhibitor, reprograms myogenic cells to acquire a pluripotent, circulating phenotype
Articolo
Data di Pubblicazione:
2007
Citazione:
Bisperoxovanadium, a phospho-tyrosine phosphatase inhibitor, reprograms myogenic cells to acquire a pluripotent, circulating phenotype / L. Castaldi, C. Serra, F. Moretti, G. Messina, R. Paoletti, M. Sampaolesi, A. Torgovnick, M. Baiocchi, F. Padula, A. Pisaniello, M. Molinaro, G. Cossu, M. Levrero, M. Bouché. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 21:13(2007), pp. 3573-3583.
Abstract:
Satellite cells are the main source of myogenic progenitors in postnatal skeletal muscle, but their use in cell therapy for muscle disorders is limited because these cells cannot be delivered through circulation and they are rapidly exhausted in severe myopathies. The search for alternative donor cells is ongoing, but none of the candidates so far show all the features required for successful colonization and repair of diseased muscle. In this study, we show that bisperoxovanadium, a phospho-tyrosine phosphatase inhibitor, induces myogenic cells to acquire a gene expression profile and a differentiation potential consistent with the phenotype of a circulating precursors, while maintaining their myogenic potential. These effects are mediated, at least in part, by NF-kappa B activation through the Tyr42-I kappa B-alpha phosphorylation, as shown by the expression of the dominant negative mutant form of the p50 NF-kappa B subunit. Moreover, when bisperoxovanadium-treated cells are injected into the femoral artery of alpha-sarcoglican null dystrophic mice, they are able to circulate and to reach muscle tissue; importantly, they contribute to muscle regeneration, as shown by the expression of alpha-sarcoglican in some fibers. Our observations indicate that bisperoxovanadium, or similar compounds, may prove very valuable to obtain and to expand, from committed cells, multipotent cell populations suitable for gene-cell therapy applications and may help to understand the molecular basis of genome reprogramming and "stem-ness".
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Cell therapy; Gene reprogramming; Muscle deseases; Satellite cells
Elenco autori:
L. Castaldi, C. Serra, F. Moretti, G. Messina, R. Paoletti, M. Sampaolesi, A. Torgovnick, M. Baiocchi, F. Padula, A. Pisaniello, M. Molinaro, G. Cossu, M. Levrero, M. Bouché
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