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Originally published in Science Express on 10 July 2003
Science 25 July 2003:
Vol. 301. no. 5632, pp. 487 - 492
DOI: 10.1126/science.1082254
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Research Articles

Cell Therapy of {alpha}-Sarcoglycan Null Dystrophic Mice Through Intra-Arterial Delivery of Mesoangioblasts

Maurilio Sampaolesi,1 Yvan Torrente,2 Anna Innocenzi,1 Rossana Tonlorenzi,1 Giuseppe D'Antona,3 M. Antonietta Pellegrino,3 Rita Barresi,4 Nereo Bresolin,2,5 M. Gabriella Cusella De Angelis,1,3 Kevin P. Campbell,4 Roberto Bottinelli,3 Giulio Cossu1,6,7*

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.

1 Stem Cell Research Institute, H. S. Raffaele, Via Olgettina 58, 20132 Milan, Italy. 2 Department of Neurological Science, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Centro Dino Ferrari, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy. 3 Department of Experimental Medicine, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy. 4 Howard Hughes Medical Institute, Department of Physiology, Biophysics and Neurology, University of Iowa College of Medicine, Iowa City, IA 52242, USA. 5 IRCCS E. Medea, Bosisio Parini, 23842 Lecco, Italy. 6 Department of Histology and Medical Embryology, University of Rome "La Sapienza," Via A. Scarpa 14, 00161 Rome, Italy. 7 Institute of Cell Biology and Tissue Engineering, San Raffaele Biomedical Science Park of Rome, Via Castel Romano 100, 00128 Rome, Italy.

* To whom correspondence should be addressed. E-mail: cossu.giulio{at}hsr.it

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Science. ISSN 0036-8075 (print), 1095-9203 (online)