Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle.
Duchenne muscular dystrophy (DMD) is a common X-linked disease characterized by widespread muscle damage that invariably leads to paralysis and death. There is currently no therapy for this disease. Here we report that a subpopulation of circulating cells expressing AC133, a well-characterized marker of hematopoietic stem cells, also expresses early myogenic markers. Freshly isolated, circulating AC133(+) cells were induced to undergo myogenesis when cocultured with myogenic cells or exposed to Wnt-producing cells in vitro and when delivered in vivo through the arterial circulation or directly into the muscles of transgenic scid/mdx mice (which allow survival of human cells). Injected cells also localized under the basal lamina of host muscle fibers and expressed satellite cell markers such as M-cadherin and MYF5. Furthermore, functional tests of injected muscles revealed a substantial recovery of force after treatment. As these cells can be isolated from the blood, manipulated in vitro, and delivered through the circulation, they represent a possible tool for future cell therapy applications in DMD disease or other muscular dystrophies.
Torrente
Yvan
Y
Stem Cell Laboratory, Department of Neurological Science, Instituto di Ricovero e Cura a Carattere Scientifico Ospedale Maggiore Policlinico, Centro Dino Ferrari, University of Milan, Italy. torrenteyvan@hotmail.com
Belicchi
Marzia
M
Sampaolesi
Maurilio
M
Pisati
Federica
F
Meregalli
Mirella
M
D'Antona
Giuseppe
G
Tonlorenzi
Rossana
R
Porretti
Laura
L
Gavina
Manuela
M
Mamchaoui
Kamel
K
Pellegrino
Maria Antonietta
MA
Furling
Denis
D
Mouly
Vincent
V
Butler-Browne
Gillian S
GS
Bottinelli
Roberto
R
Cossu
Giulio
G
Bresolin
Nereo
N
D000071916:AC133 Antigen; D000293:Adolescent; D000328:Adult; D000818:Animals; D015703:Antigens, CD; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology; D017690:Cell Transplantation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D051379:Mice; D018101:Mice, Inbred mdx; D016513:Mice, SCID; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010455:Peptides / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins
D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D016189:Dystrophin; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins