Titre :
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Abundance of circulating progenitors with myo-endothelial potential correlates with a mild phenotype in patients affected by Duchenne muscular dystrophy : Actes de colloque : Congrès international de myologie 2008 (International Congress of Myology 2008) 26-30 mai 2008 - Marseille
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contenu dans :
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Auteurs :
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Belicchi M ;
Meregalli M ;
Marchesi C ;
Lopa R ;
Porretti L ;
Parolini D ;
D'Angelo MG ;
Bresolin N ;
Torrente Y
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Type de document :
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Article
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Année de publication :
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2008
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Pages :
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p. 100
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Langues:
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Anglais
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Mots-clés :
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âge
;
colloque
;
corrélation génotype-phénotype
;
dystrophie musculaire de Duchenne
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fonction musculaire
;
insuffisance cardiaque
;
insuffisance respiratoire
;
muscle squelettique
;
myoblaste
;
myocarde
;
souris mdx
;
thérapie cellulaire
;
traumatisme musculaire
;
variabilité clinique
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Résumé :
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Although the natural history of patients with Duchenne Muscular dystrophy (DMD) is characterized by a progressive impairment of muscle function leading to death for cardio-pulmonary failure, there is a clinical variability in these patients regarding age of onset, patterns of skeletal muscle involvement, heart damage, and rate of progression. Most therapeutic strategies for DMD have been palliative rather than curative. Experimental treatments in DMD are difficult due the absence of reliable biomarkers that could be prognostic of the progression of the disease or response to the treatment. Recent works from several laboratories support the idea that increased circulating endothelial progenitors predict cardiovascular and vascular diseases. We hypothesized that the levels of circulating stem cells expressing the CD133 antigen which possess myo/endothelial potential would predict the progression of DMD. The count of circulating CD133+ stem cells was similar in DMD patients and healthy subjects. We found a subpopulation of CD133+ stem cells also expressing the CXCR4 receptor but not CD34 that was significantly higher in DMD patients compared with healthy controls and positively correlated with the clinical score. DMD patients exhibiting mild phenotype have higher levels of this subpopulation of circulating CD133+ stem cells than patients exhibiting severe phenotype. Linear regression analysis showed a direct correlation between the levels of these cells and the clinical condition of the DMD patients. The circulating AC133+CXCR4+CD34- cells isolated from DMD and healthy subjects express early myogenic and endothelial markers in vitro and differentiate into muscle and endothelial cells in vivo after their transplantation into scid/mdx dystrophic mice. Based on these data we believe that the levels of a subpopulation of circulating CD133+ stem cells in DMD patients may be a promising new prognostic clinical marker of the progression of the disease with practical significance to allow any beneficial effect in future clinical trials.
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