Dermal fibroblasts convert to a myogenic lineage in mdx mouse muscle
| Autor: | Alexander J. Gibson, Diana J. Watt, Tim G. Sherratt, Peter N. Strong, Jill Moss, J Karasinski, João B. Relvas |
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| Rok vydání: | 1995 |
| Předmět: |
mdx mouse
Time Factors Cell Transplantation Cellular differentiation Duchenne muscular dystrophy Biology Muscular Dystrophies Dystrophin Mice Organ Culture Techniques medicine Animals Humans Myocyte Muscular dystrophy Muscle Skeletal Skin Sarcolemma Cell Differentiation Genetic Therapy Cell Biology Fibroblasts Muscular Dystrophy Animal medicine.disease Clone Cells Cell biology Mice Inbred C57BL Animals Newborn Immunology Mice Inbred mdx biology.protein ITGA7 |
| Zdroj: | Journal of Cell Science. 108:207-214 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.108.1.207 |
| Popis: | Duchenne muscular dystrophy is a primary muscle disease that manifests itself in young boys as a result of a defect in a gene located on the X-chromosome. This gene codes for dystrophin, a normal muscle protein that is located beneath the sarcolemma of muscle fibres. Therapies to alleviate this disease have centred on implanting normal muscle precursor cells into dystrophic fibres to compensate for the lack of this gene and its product. To date, donor cells for implantation in such therapy have been of myogenic origin, derived from paternal biopsies. Success in human muscle, however, has been limited and may reflect immune rejection problems. To overcome this problem the patient's own myogenic cells, with the dystrophin gene inserted, could be used, but this could lead to other problems, since these cells are those that are functionally compromised by the disease. Here, we report the presence of high numbers of dystrophin-positive fibres after implanting dermal fibroblasts from normal mice into the muscle of the mdx mouse-the genetic homologue of Duchenne muscular dystrophy. Dystrophin-positive fibres were also abundant in mdx muscle following the implantation of cloned dermal fibroblasts from the normal mouse. Our results suggest the in vivo conversion of these non-myogenic cells to the myogenic pathway resulting in the formation of dystrophin-positive muscle fibres in the deficient host. The use of dermal fibroblasts may provide an alternative approach to the previously attempted myoblast transfer therapy, which in human trials has yielded disappointing results. |
| Databáze: | OpenAIRE |
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