Résumé :
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Communication n° 1 Introduction : Used appropriately, myoblast transplantation (MT) could be a potential therapeutic tool in the treatment of myopathies: it can induce the expression of donor proteins in the myofibers of the recipient, and it can increase the myogenic capital in wasted muscles. In non-human primate experiments, two MT conditions were important to produce the expression of donor proteins in high numbers of the recipient's myofibers: (1) donor-cell delivery by a technique of high-density intramuscular injections, and (2) appropriate immunosuppression. Objectives. To test in DMD patients MT conditions similar to those successfully used in non-human primate experiments. Methods : Nine DMD patients received myoblast injections obtained from skeletal muscle biopsies of normal donors. Cells were injected in 1 cm3 or less of the Tibialis anterior by 25 or 100 parallel injections. Similar patterns of saline injections were performed in the contralateral muscles. The patients received tacrolimus for immunosuppression. Muscle biopsies were performed at the injected sites 4 weeks later. Results : We observed donor-dystrophin-positive myofibers or a significant increase of dystrophin-positive myofibers only in the cell-grafted sites of 8 patients. The percentage of donor-dystrophin positive myofibers, for the total number of myofibers in the biopsies, varied from 3 to 26 %. Donor-dystrophin transcripts or a significant increase of dystrophin transcripts were detected by RT-PCR only in the cell-grafted sites of all 9 patients. Conclusions : Our results show that significant dystrophin expression can be obtained in the skeletal muscles of DMD patients following specific conditions of cell delivery (high-density intramuscular injections) and an appropriate control of acute rejection.
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