Cyclophosphamide immunosuppression does not permit successful myoblast allotransplantation in mouse.
Cyclophosphamide immunosuppression does not permit successful myoblast allotransplantation in mouse. Myoblast transplantation is a potential treatment for Duchenne muscular dystrophy. In one clinical trial, Duchenne patients were immunosuppressed with cyclophosphamide. We report here that myoblasts from transgenic mice expressing the beta-galactosidase reporter gene transplanted in mdx mice failed to form new muscle fibres when cyclophosphamide (2 or 10 mg kg-1 per day) was used for immunosuppression. At the lowest dose of cyclophosphamide (2 mg kg-1 per day), some mdx recipient mice formed antibodies against donor myoblasts; however, no humoral immune reaction was observed at the highest dose (10 mg kg-1 per day). The failure of transplantation under cyclophosphamide treatment was attributed to the low immunosuppressive activity at a low dose and to the toxic action of a high dose of this drug. These results could explain the lack of success of myoblast transplantation in a previous clinical trial.
Vilquin
J T
JT
Laboratoire de neurobiologie, Université Laval, Québec, Canada.
Kinoshita
I
I
Roy
R
R
Tremblay
J P
JP
D000818:Animals; D017690:Cell Transplantation / Q000502:physiology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D016189:Dystrophin / Q000096:biosynthesis; D005434:Flow Cytometry; D017930:Genes, Reporter; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000637:transplantation*; D014182:Transplantation, Autologous; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D016189:Dystrophin; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001616:beta-Galactosidase