Dystrophin expression in muscles of duchenne muscular dystrophy patients after high-density injections of normal myogenic cells.
A clinical trial was conducted to test a new protocol of normal muscle precursor cell (MPC) allotransplantation in skeletal muscles of patients with Duchenne muscular dystrophy (DMD). Cultured MPCs obtained from one of the patient's parents were implanted in 0.25 or 1 cm of a Tibialis anterior in 9 patients with DMD. MPC injections were placed 1 to 2 mm from each other, and a similar pattern of saline injections was done in the contralateral muscle. The patients were immunosuppressed with tacrolimus. Muscle biopsies were performed at the injected sites 4 weeks later. In the biopsies of the cell-grafted sites, there were myofibers expressing donor's dystrophin in 8 patients. The percentage of myofibers expressing donor's dystrophin varied from 3.5% to 26%. Evidence of small myofiber neoformation was observed in some patients. Donor-derived dystrophin transcripts were detected by reverse transcriptase-polymerase chain reaction in the cell-grafted sites in all patients. The protocol of immunosuppression was sufficient to obtain these results, although it is not certain whether acute rejection was efficiently controlled in all the cases. In conclusion, intramuscular allotransplantation of normal MPCs can induce the expression of donor-derived dystrophin in skeletal muscles of patients with DMD, although this expression is restricted to the sites of MPC injection.
Skuk
Daniel
D
Human Genetic Research Unit, Laval University Hospital Center, Quebec, Canada.
Goulet
Marlyne
M
Roy
Brigitte
B
Chapdelaine
Pierre
P
Bouchard
Jean-Pierre
JP
Roy
Raynald
R
Dugré
Francine J
FJ
Sylvain
Michel
M
Lachance
Jean-Guy
JG
Deschênes
Louise
L
Senay
Hélène
H
Tremblay
Jacques P
JP
D000293:Adolescent; D000818:Animals; D002648:Child; D016189:Dystrophin / Q000096:biosynthesis* / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000517:prevention & control; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D016513:Mice, SCID; D032342:Muscle Cells / Q000276:immunology / Q000637:transplantation*; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D016559:Tacrolimus / Q000627:therapeutic use
D016189:Dystrophin; D006649:Histocompatibility Antigens; D007166:Immunosuppressive Agents; D016559:Tacrolimus