title: Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle.
abstract: 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.
authors.affiliation: 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
authors.forename: Yvan
authors.initials: Y
authors.lastname: Torrente
authors.forename: Marzia
authors.initials: M
authors.lastname: Belicchi
authors.forename: Maurilio
authors.initials: M
authors.lastname: Sampaolesi
authors.forename: Federica
authors.initials: F
authors.lastname: Pisati
authors.forename: Mirella
authors.initials: M
authors.lastname: Meregalli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Antona
authors.forename: Rossana
authors.initials: R
authors.lastname: Tonlorenzi
authors.forename: Laura
authors.initials: L
authors.lastname: Porretti
authors.forename: Manuela
authors.initials: M
authors.lastname: Gavina
authors.forename: Kamel
authors.initials: K
authors.lastname: Mamchaoui
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Pellegrino
authors.forename: Denis
authors.initials: D
authors.lastname: Furling
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Butler-Browne
authors.forename: Roberto
authors.initials: R
authors.lastname: Bottinelli
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
mesh_terms: 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
chemical_list: 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