| Autor: |
Huard, Christine, Moisset, Pierre-Alain, Dicaire, Annie, Merly, Franck, Tardif, François, Asselin, Isabelle, Tremblay, Jacques P. |
| Zdroj: |
Biochemical and Biophysical Research Communications; July 1998, Vol. 248 Issue: 3 p648-654, 7p |
| Abstrakt: |
Transplantation of normal myoblasts into dystrophic muscles is a potential treatment for Duchenne muscular dystrophy (DMD). However, the success of such grafts is limited by the immune system responses. To avoid rejection problems, autologous transplantation of the patient's corrected myoblasts has been proposed. Regretfully, the low proliferative capacity of DMD myoblasts in culture (due to their premature senescence) limits such procedure. On the other hand, modification of dermal fibroblasts leading to the myogenic pathway using a master regulatory gene for myogenesis is an interesting alternative approach. In this study, the retrovirally encoded MyoD1 cDNA was introduced in dermal fibroblasts of TnI LacZ mice to provoke their conversion into myoblast-like cells.In vitroandin vivoassays were done and the results were compared to those obtained with uninfected fibroblasts and myoblasts. Some MyoD1-expressing fibroblasts were able to fuse and to express β-galactosidase (under the transcriptionnal control of the Troponin I promoter), dystrophin and desminin vitro.Thirty days following implantation of these modified fibroblasts in muscles of mdx mice, an average of 7 β-Gal+/Dys− muscle fibers were observed. No β-Gal+ fibers were observed after the transplantation of uninfected fibroblasts. Our results indicate that the successful implantation of myoblasts obtained from genetically modified fibroblasts is indeed feasible. However, thein vitroconversion rate and thein vivofusion of genetically modified fibroblasts must be largely increased to consider this approach as a potential therapy for DMD and other myopathies. |
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