Mature adult dystrophic mouse muscle environment does not impede efficient engrafted satellite cell regeneration and self-renewal.
Changes that occur in the skeletal muscle environment with the progress of muscular dystrophies may affect stem cell function and result in impaired muscle regeneration. It has previously been suggested that the success of stem cell transplantation could therefore be dependent both on the properties of the cell itself and on the host muscle environment. Here we engrafted young and mature adult mdx-nude mice, which are the genetic homolog of Duchenne muscular dystrophy, with a small number of satellite cells freshly isolated from young, normal donor mice. We found that the donor satellite cells contributed to muscle regeneration and self-renewal as efficiently within mature adult, as in young, dystrophic host muscle. Donor-derived satellite cells also contributed to robust regeneration after further injury, showing that they were functional despite the more advanced dystrophic muscle environment. These findings provide evidence that muscle tissue in a later stage of dystrophy may be effectively treated by stem cells.
Boldrin
Luisa
L
Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, United Kingdom.
Zammit
Peter Steven
PS
Muntoni
Francesco
F
Morgan
Jennifer Elizabeth
JE
D000367:Age Factors; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D006085:Graft Survival / Q000502:physiology*; D051379:Mice; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000601:surgery*; D012038:Regeneration / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome
D009124:Muscle Proteins