Myoblast transplantation in whole muscle of nonhuman primates.
The goal of the present study was to determine the feasibility, success, and toxicity of myoblast transplantation (MT) in the whole muscle of primates. Allogenic myoblasts transduced with the beta-galactosidase (beta-Gal) gene were transplanted in the whole Biceps brachii of 5 monkeys immunosuppressed with FK506. Myoblast injections were spaced at every 1 to 1.5 mm in 7 muscles, as well as at every 5 mm in 2 muscles. Myoblasts were resuspended in HBSS, notexin 1 microg/ml or notexin 5 microg/ml. Depending on the number of beta-Gal labeled myoblasts and the injection protocol, biopsies of transplanted muscles exhibited 7% to 74% beta-Gal+ fibers 1 month after MT. Beta-Gal+ fibers were present in muscle biopsies made 3, 8, and 12 months after MT. Myoglobinuria and hyperkalemia, the risk factors after extensive muscle damage and notexin toxicity, were not observed. The withdrawal of immunosuppression led to histological evidences of cellular rejection of the graft. We concluded that MT can be successfully performed in large primate muscles without toxicity due to muscle damage. An effective immunosuppression allowed the maintenance of beta-Gal+ fibers up to 1 year after MT. These results suggest parameters that may allow effective MT in humans.
Skuk
D
D
Unité de recherche en Génétique humaine, Centre de Recherche du Centre Hospitalier de l'Université Laval, Ste-Foy, Québec, Canada.
Goulet
M
M
Roy
B
B
Tremblay
J P
JP
D000818:Animals; D001706:Biopsy; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D004546:Elapid Venoms; D017930:Genes, Reporter; D006084:Graft Rejection / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008253:Macaca mulatta; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D018482:Muscle, Skeletal / Q000473:pathology / Q000601:surgery*; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology / Q000601:surgery; D016559:Tacrolimus / Q000494:pharmacology; D001616:beta-Galactosidase / Q000235:genetics
D004546:Elapid Venoms; D007166:Immunosuppressive Agents; C005082:notexin; D001616:beta-Galactosidase; D016559:Tacrolimus