Efficacy of myoblast transplantation in nonhuman primates following simple intramuscular cell injections: toward defining strategies applicable to humans.
Nonhuman primates were used to define myoblast transplantation strategies applicable to humans. Nevertheless, previous experiments were based on the use of myotoxins concomitant with the myoblast injections. Since myotoxins must be avoided for clinical applications, we analyzed the efficacy of simple myoblast injections (i.e., myoblasts resuspended only in saline) into monkey muscles. We also evaluated different FK506 dosages (in combination or not with mycophenolate mofetil) for immunosuppression. Allogeneic myoblasts transduced with the beta-galactosidase (beta-Gal) gene were implanted in the muscles of 19 monkeys by injections placed 1 to 2 mm from each other. A biopsy was performed at the implanted sites 1 month later, and histologically studied for demonstration of beta-Gal+ myofibers, lymphocyte infiltration, and CD8+ cells. The presence of antibodies against the donor myoblasts and the blood levels of FK506 were analyzed. Our results show that: (1) If myoblast injections are sufficiently close to each other, high percentages of hybrid myofibers can be obtained following myoblast transplantation in primates (25 to 67% with an interinjection distance of 1 mm). (2) Efficient immunosuppression can be reached by increasing FK506 dosages, but also by combining this drug with mycophenolate mofetil, a combination that reduces toxic effects. The present results represent a step towards a better designing of myoblast transplantation strategies in humans.
Skuk
Daniel
D
Unité de recherche en Génétique humaine, Centre de Recherche du Centre, Hospitalier de l'Université Laval, CHUQ pavillon CHUL, 2705 boulevard Laurier, Ste-Foy, Québec, G1V 4G2, Canada.
Goulet
Marlyne
M
Roy
Brigitte
B
Tremblay
Jacques P
JP
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D017930:Genes, Reporter; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D018482:Muscle, Skeletal / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D007166:Immunosuppressive Agents; D001616:beta-Galactosidase; D009173:Mycophenolic Acid; D016559:Tacrolimus