title: Human skeletal muscle-derived CD133(+) cells form functional satellite cells after intramuscular transplantation in immunodeficient host mice.
abstract: Stem cell therapy is a promising strategy for treatment of muscular dystrophies. In addition to muscle fiber formation, reconstitution of functional stem cell pool by donor cells is vital for long-term treatment. We show here that some CD133(+) cells within human muscle are located underneath the basal lamina of muscle fibers, in the position of the muscle satellite cell. Cultured hCD133(+) cells are heterogeneous and multipotent, capable of forming myotubes and reserve satellite cells in vitro. They contribute to extensive muscle regeneration and satellite cell formation following intramuscular transplantation into irradiated and cryodamaged tibialis anterior muscles of immunodeficient Rag2-/γ chain-/C5-mice. Some donor-derived satellite cells expressed the myogenic regulatory factor MyoD, indicating that they were activated. In addition, when transplanted host muscles were reinjured, there was significantly more newly-regenerated muscle fibers of donor origin in treated than in control, nonreinjured muscles, indicating that hCD133(+) cells had given rise to functional muscle stem cells, which were able to activate in response to injury and contribute to a further round of muscle regeneration. Our findings provide new evidence for the location and characterization of hCD133(+) cells, and highlight that these cells are highly suitable for future clinical application.
authors.affiliation: The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Meng
authors.affiliation: The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK.
authors.forename: Soyon
authors.initials: S
authors.lastname: Chun
authors.affiliation: The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK.
authors.forename: Rowan
authors.initials: R
authors.lastname: Asfahani
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK.
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.affiliation: The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.affiliation: The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Morgan
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D064987:Cell- and Tissue-Based Therapy; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D009136:Muscular Dystrophies / Q000235:genetics / Q000628:therapy*; D017570:MyoD Protein / Q000096:biosynthesis; D032446:Myoblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000235:genetics*; D012038:Regeneration / Q000235:genetics / Q000276:immunology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D033581:Stem Cell Transplantation
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse