Heat shock treatment increases engraftment of transplanted human myoblasts into immunodeficient mice.
Myoblast transfer therapy (MTT) is a strategy that has been proposed to treat some striated muscle pathologies. However, the first therapeutic trials using this technique were unsuccessful due to the limited migration and early cell death of the injected myoblasts. Various strategies have been considered to increase myoblast survival in the host muscle after MTT. Overexpression of heat shock proteins (HSPs) in mouse myoblasts has been shown to improve cell resistance against apoptosis in vitro and in vivo. Our objective was to determine whether heat shock (HS) treatment increased the survival of human myoblasts leading to better participation of the injected cells in muscle regeneration. For this study, HS-treated human myoblasts were injected into the tibialis anterior (TA) muscles of immunodeficient RAG-/- gammaC-/- mice. TA muscles were excised at 24 hour and at 1 month after injection. Our results showed that HS treatment increased the expression of the hsp70 protein and protected the cells from apoptosis in vitro. HS treatment dramatically increased the number of human fibers present at 1 month after injection when compared with nontreated cells. Interestingly, HS treatment decreased apoptosis at 24 hour after human myoblast injection, but no differences were observed concerning proliferation, suggesting that the increased fiber formation among the HS-treated group was probably due to decreased cell death. These data suggested that HS treatment might be used in the clinical context to improve the success of MTT.
Riederer
I
I
UMR S 787, Institut de Myologie, INSERM & Université Pierre et Marie Curie, Paris, France.
Negroni
E
E
Bigot
A
A
Bencze
M
M
Di Santo
J
J
Aamiri
A
A
Butler-Browne
G
G
Mouly
V
V
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006085:Graft Survival / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D009135:Muscular Diseases / Q000601:surgery; D032446:Myoblasts / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D014183:Transplantation, Heterologous / Q000502:physiology*; D016896:Treatment Outcome
D005819:Genetic Markers; D018840:HSP70 Heat-Shock Proteins