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Cell therapy of alpha-sarcoglycan null dystrophic mice through intra-arterial delivery of mesoangioblasts
Authors:Sampaolesi Maurilio  Torrente Yvan  Innocenzi Anna  Tonlorenzi Rossana  D'Antona Giuseppe  Pellegrino M Antonietta  Barresi Rita  Bresolin Nereo  De Angelis M Gabriella Cusella  Campbell Kevin P  Bottinelli Roberto  Cossu Giulio
Affiliation:Stem Cell Research Institute, H. S. Raffaele, Via Olgettina 58, 20132 Milan, Italy.
Abstract:Preclinical or clinical trials for muscular dystrophies have met with modest success, mainly because of inefficient delivery of viral vectors or donor cells to dystrophic muscles. We report here that intra-arterial delivery of wild-type mesoangioblasts, a class of vessel-associated stem cells, corrects morphologically and functionally the dystrophic phenotype of virtually all downstream muscles in adult immunocompetent alpha-sarcoglycan (alpha-SG) null mice, a model organism for limb-girdle muscular dystrophy. When mesoangioblasts isolated from juvenile dystrophic mice and transduced with a lentiviral vector expressing alpha-SG were injected into the femoral artery of dystrophic mice, they reconstituted skeletal muscle in a manner similar to that seen in wild-type cells. The success of this protocol was mainly due to widespread distribution of donor stem cells through the capillary network, a distinct advantage of this strategy over previous approaches.
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