Myoblast transplantation in whole muscle of nonhuman primates

The goal of the present study was to determine the feasibility, success, an d toxicity of myoblast transplantation (MT) in the whole muscle of primates . Allogenic myoblasts transduced with the beta-galactosidase (beta-Gal) gen e were transplanted in the whole Biceps brachii of 5 monkeys immunosuppress ed with FK506. Myoblast injections were spaced at every 1 to 1.5 mm in 7 mu scles, as well as at every 5 mm in 2 muscles. Myoblasts were resuspended in HBSS, notexin 1 mu g/ml or notexin 5 mu g/ml. Depending on the number of b eta-Gal labeled myoblasts and the injection protocol, biopsies of transplan ted 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 da mage and notexin toxicity, were not observed. The withdrawal of immunosuppr ession led to histological evidences of cellular rejection of the graft. We concluded that MT can be successfully performed in large primate muscles w ithout toxicity due to muscle damage. An effective immunosuppression allowe d the maintenance of beta-Gal+ fibers up to 1 year after MT. These results suggest parameters that may allow effective MT in humans.