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Karpati, G. et al. Dystrophin is expressed in mdx skeletal muscle fibers after normal myoblast implantation. Am. J. Pathol. 135, 27-32

Neuromuscular Research Group, Montreal Neurological Institute, McGill University, Quebec, Canada.
American Journal Of Pathology (Impact Factor: 4.6). 08/1989; 135(1):27-32.
Source: PubMed

ABSTRACT In mdx mice, the dystrophin gene of the X chromosome is defective and, as a result, immunoreactive dystrophin is undetectable in all muscle fibers of all animals of this highly inbred strain. This study showed that implantation of suspensions of clonal cultures of normal human myoblasts into different regions of quadriceps muscles of 6-to-10-day-old mdx mice or 60-day-old mdx mice (whose muscles have been crushed 4 days before implantation) results in the appearance of scattered fiber segments containing microscopically demonstrable immunoreactive dystrophin. In the animals that received the normal myoblast implantation in the prenecrotic stage of the disease (6 to 10 days of age), the dystrophin-positive fiber segments (demonstrated at ages 35, 45, and 60 days) escaped necrosis. This was determined by the absence of the characteristic chains of central nuclei, a reliable marker of prior necrosis in mdx muscle fibers. By heavy labeling of the nuclear DNA of the transplantable human myoblasts with H3-thymidine during culturing, and by sequential performance of an immunocytochemical staining for dystrophin and autoradiography on the same sections, some dystrophin-positive fiber segments were shown to contain radiolabeled myonuclei. It was concluded that nondystrophic myoblasts fused with host muscle fibers to form mosaic muscle fibers in which the normal dystrophin gene of the implanted myoblasts was expressed. This approach may be employed for the mitigation of the deleterious consequences of a gene defect in recessively inherited human muscle diseases such as Duchenne dystrophy.

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    • "They detected dystrophin in several myofibers after followups of at least 3 weeks. Similar results were reported thereafter by other researchers [8] [9], and this has become a routine in the research of myogenic-cell transplantation. Gene complementation in myofibers of humans was unequivocally confirmed in at least 3 clinical trials of myoblast transplantation [10] [11] [12] [13] (Figure 2). "
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    10/2013; 2013. DOI:10.5402/2013/582689
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    • "Satellite cells are quiescent cells, located under the basal lamina of muscle fibres [5] [6] [7] [8] that can be activated to give a pool of progeny muscle precursor cells, or myoblasts [9] [10] [11]. Myoblasts can be expanded in tissue culture and contribute to limited muscle regeneration following direct intra-muscular transplantation [12] [13] [14] [15] [16] [17] [18]. 2. Stem cell therapy for muscular dystrophies "
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    Neuromuscular Disorders 11/2010; 21(1):4-12. DOI:10.1016/j.nmd.2010.10.004 · 3.13 Impact Factor
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    • "Duchenne muscular dystrophy (DMD), which is caused by mutations in the dystrophin gene, is a progressive muscle-wasting disorder characterized by continuous degeneration of muscle fibers and an eventual loss of muscle function owing to the infiltration of connective tissue (Koenig et al., 1987). Among other therapeutic approaches, over the past two decades there has been considerable experimentation with cell-based therapy as a means to treat DMD (Law et al., 1988; Karpati et al., 1989; Partridge et al., 1989). This strategy involves transplanting cells that produce a functional copy of dystrophin into an affected individual so that the donor cells can provide gene products normally absent or non-functional in the recipient. "
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