1. San Raffaele Scientific Institute, Università Vita e Salute, Stem Cell Research Institute, Via Olgettina 58, 20132 Milan, Italy
2. Department of Experimental Medicine and Interuniversity Institute of Myology, University of Pavia, Via Forlanini 6-8, 27100 Pavia, Italy
3. Neurobiology Laboratory, École Vétérinaire d'Alfort, 7 Avenue Général de Gaulle, 94704 Maisons-Alfort cedex, France
4. Department of Bioengineering, Politecnico di Milano, Piazza Leonardo Da Vinci, 20130 Milan, Italy
5. Institute of Cell Biology and Tissue Engineering, San Raffaele Biomedical Science Park of Rome, Via Castel Romano 100, 00128 Rome, Italy
6. IRCCS Fondazione Policlinico di Milano, Department of Neurological Sciences, University of Milan, Via Sforza 35, 20122 Milan, Italy
7. Department of Biology and Centre for Stem Cell Research, University of Milan, Via Celoria 28, 20130 Milan, Italy
8. These authors contributed equally to this work.

Correspondence to: Roberto Bottinelli²Giulio Cossu^1,5,7 Correspondence and requests for materials should be addressed to C.G. (Email: cossu.giulio@hsr.it) or R.B. (Email: roberto.bottinelli@unipv.it).

Abstract

Duchenne muscular dystrophy remains an untreatable genetic disease that severely limits motility and life expectancy in affected children. The only animal model specifically reproducing the alterations in the dystrophin gene and the full spectrum of human pathology is the golden retriever dog model. Affected animals present a single mutation in intron 6, resulting in complete absence of the dystrophin protein, and early and severe muscle degeneration with nearly complete loss of motility and walking ability. Death usually occurs at about 1 year of age as a result of failure of respiratory muscles. Here we report that intra-arterial delivery of wild-type canine mesoangioblasts (vessel-associated stem cells) results in an extensive recovery of dystrophin expression, normal muscle morphology and function (confirmed by measurement of contraction force on single fibres). The outcome is a remarkable clinical amelioration and preservation of active motility. These data qualify mesoangioblasts as candidates for future stem cell therapy for Duchenne patients.

1. San Raffaele Scientific Institute, Università Vita e Salute, Stem Cell Research Institute, Via Olgettina 58, 20132 Milan, Italy
2. Department of Experimental Medicine and Interuniversity Institute of Myology, University of Pavia, Via Forlanini 6-8, 27100 Pavia, Italy
3. Neurobiology Laboratory, École Vétérinaire d'Alfort, 7 Avenue Général de Gaulle, 94704 Maisons-Alfort cedex, France
4. Department of Bioengineering, Politecnico di Milano, Piazza Leonardo Da Vinci, 20130 Milan, Italy
5. Institute of Cell Biology and Tissue Engineering, San Raffaele Biomedical Science Park of Rome, Via Castel Romano 100, 00128 Rome, Italy
6. IRCCS Fondazione Policlinico di Milano, Department of Neurological Sciences, University of Milan, Via Sforza 35, 20122 Milan, Italy
7. Department of Biology and Centre for Stem Cell Research, University of Milan, Via Celoria 28, 20130 Milan, Italy
8. These authors contributed equally to this work.

Correspondence to: Roberto Bottinelli²Giulio Cossu^1,5,7 Correspondence and requests for materials should be addressed to C.G. (Email: cossu.giulio@hsr.it) or R.B. (Email: roberto.bottinelli@unipv.it).

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