Bisperoxovanadium, a phospho‐tyrosine phosphatase inhibitor, reprograms myogenic cells to acquire a pluripotent, circulating phenotype

• Published in: The FASEB journal 2007-11, Vol.21 (13), p.3573-3583
• Main Authors: Castaldi, L., Serra, C., Moretti, F., Messina, G., Paoletti, R., Sampaolesi, M., Torgovnick, A., Baiocchi, M., Padula, F., Pisaniello, A., Molinaro, M., Cossu, G., Levrero, M., Bouché, M.
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Cell Cycle; Cell Line; cell therapy; DNA Primers; Enzyme Inhibitors - pharmacology; Flow Cytometry; Fluorescent Antibody Technique; Gene Expression; gene reprogramming; Heart - drug effects; Mice; muscle deseases; Myocardium - cytology; Myocardium - metabolism; Phenotype; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Protein Tyrosine Phosphatases - antagonists & inhibitors; Reverse Transcriptase Polymerase Chain Reaction; satellite cells; Vanadium Compounds - pharmacology
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.06-7454com

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 myopa‐thies. 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 bisperox‐ovanadium, 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‐κB activation through the Tyr42‐IκB‐α phosphorylation, as shown by the expression of the dominant negative mutant form of the p50 NF‐κB subunit. Moreover, when bisperoxova‐nadium‐treated cells are injected into the femoral artery of α‐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 α‐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.”—Castaldi, L., Serra, C., Moretti, F., Messina, G., Paoletti, R., Sampaolesi, M., Torgovnick, A., Baiocchi, M., Padula, F., Pisaniello, A., Molinaro, M., Cossu, G., Levrero, M., Bouché, M. Bisperoxovanadium, a phospho‐tyrosine phosphatase inhibitor, reprograms myogenic cells to acquire a plu‐ripotent, circulating phenotype. FASEB J. 21, 3573–3583 (2007)