Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs.
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.
Sampaolesi
Maurilio
M
San Raffaele Scientific Institute, Università Vita e Salute, Stem Cell Research Institute, Via Olgettina 58, 20132 Milan, Italy.
Blot
Stephane
S
D'Antona
Giuseppe
G
Granger
Nicolas
N
Tonlorenzi
Rossana
R
Innocenzi
Anna
A
Mognol
Paolo
P
Thibaud
Jean-Lauren
JL
Galvez
Beatriz G
BG
Barthélémy
Ines
I
Perani
Laura
L
Mantero
Sara
S
Guttinger
Maria
M
Pansarasa
Orietta
O
Rinaldi
Chiara
C
Cusella De Angelis
M Gabriella
MG
Torrente
Yvan
Y
Bordignon
Claudio
C
Bottinelli
Roberto
R
Cossu
Giulio
G
D053687:Adult Stem Cells / Q000276:immunology / Q000637:transplantation*; D000818:Animals; D003131:Combined Modality Therapy; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D016189:Dystrophin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D032342:Muscle Cells; D009137:Muscular Dystrophy, Animal / Q000628:therapy*; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous
D016189:Dystrophin; D011993:Recombinant Fusion Proteins; D003402:Creatine Kinase