Normal myoblast injections provide genetic treatment for murine dystrophy

Law, Peter K.; Goodwin, Tena G.; Wang, Mary G.

doi:10.1002/mus.880110602

Cited by 114 publications

(35 citation statements)

References 39 publications

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“…If the contractile properties of dystrophic muscle fibres are not compromised by the lack of dystrophin as we have shown, but rather non-specifically by the degeneration/regeneration processes, then procedures aimed at halting or reversing these deleterious cycles may represent sufficient treatment strategy. For example, the implantation of normal myoblasts into dystrophic muscle results in mosaic fibres possessing normal and dystrophic nuclei (Law, Goodwin & Wang, 1988;Karpati, Pouliot, Carpenter & Holland, 1989;Partridge, Morgan, Coulton, Hoffman & Kunkel, 1989;Huard, Labrecque, Dansareau, Robitaille & Tremblay, 1991), which can express dystrophin, and potentially reduce any susceptibility of the muscle fibre membrane to suffer stressinduced injury. If such treatments are carried out before significant deterioration in muscle function is detected then it is apparent from the results presented here, and in our related studies of muscle function in other dystrophies (Fink et al 1986(Fink et al , 1990Head et al 1990) that muscle function will be preserved at near-normal levels.…”

Section: Discussionmentioning

confidence: 99%

Contractile properties of skinned muscle fibres from young and adult normal and dystrophic (mdx) mice.

Williams¹,

Head²,

Lynch³

et al. 1993

The Journal of Physiology

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SUMMARY1. Single muscle fibres were enzymatically isolated from the soleus and extensor digitorum longus (EDL) muscles of genetically dystrophic mdx and normal (C57BL/10) mice aged 3-6 or 17-23 weeks.2. Fibres of both muscles were chemically skinned with the non-ionic detergent Triton X-100 (2 % v/v). Ca2+-and Sr21-activated contractile responses were recorded and comparisons were made between several contractile parameters of various fibre types of normal and dystrophic mice of similar age.3. There were no significant differences in the following contractile parameters of skinned fibres of normal and mdx mice of the same age: sensitivity to activating Ca21 (pCa50) or Sr2" (pSr50) and differential sensitivity to the activating ions (pCa50-pSr50).However the maximum isometric tension (P.) and the frequenev of myofibrillar force oscillations in EDL fast-twitch fibres of young mdx mice were significantly lower than those of soleus fast-twitch fibres of the same animals, or fast-twitch fibres (EDL or soleus) of normal mice.4. Age-related differences were apparent in some contractile parameters of both normal and mdx mice. In particular the steepness of force-pCa anid force-pSr curves increased with age in normal mice. yet decreased with age in fibres of mdx mice. 5. A fluorescent probe, ethidium bromide, which interchelates with DNA, was used with laser-scanning confocal microscopy to determine the distribution of myonuclei in fibres. Fibres isolated from either muscle type of normal animnals displayed a characteristic peripheral spiral of myonuclei. Fibres from muscles of m1dx mice displayed three major patterns of nuclear distribution: the normal peripheral spiral, long central strands of nuclei, and a mixture of these two patterns.6. The contractile characteristics of mdx fibres were not markedly influenced by the nuclear distribution pattern in that there were no discernible differences in the major contractile parameters (the Hill coefficients nCa and nSr, which are associated with the steepness of the Ca2' and Sr2+ activation curves, pCa50, pSr50, pCa50-pSr50) of skinned fibres possessing peripheral or central nuclei. However, except for nSr, these values were all lower in individual fibres which displayed similar proportions of central and peripheral nuclei. The presence of mixed nucleation and absence of MS 9920

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Section: Discussionmentioning

confidence: 99%

Contractile properties of skinned muscle fibres from young and adult normal and dystrophic (mdx) mice.

Williams¹,

Head²,

Lynch³

et al. 1993

The Journal of Physiology

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“…The residual CAT activity observed in pIEB217CAT-transfected myotubes may be due to a pseudo-TATA box (positions -147 to -152 in Fig. 5 (39,59).…”

Section: Methodsmentioning

confidence: 99%

Molecular and functional analysis of the muscle-specific promoter region of the Duchenne muscular dystrophy gene.

Klamut¹,

Gangopadhyay²,

Worton³

et al. 1990

Mol. Cell. Biol.

133

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“…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.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow side population cells are enriched for progenitors capable of myogenic differentiation

Luth

Jun

Wessen

et al. 2008

Journal of Cell Science

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Although the contribution of bone marrow-derived cells to regenerating skeletal muscle has been repeatedly documented, there remains considerable debate as to whether this incorporation is exclusively a result of inflammatory cell fusion to regenerating myofibers or whether certain populations of bone marrow-derived cells have the capacity to differentiate into muscle. The present study uses a dual-marker approach in which GFP+ cells were intravenously transplanted into lethally irradiated β-galactosidase+ recipients to allow for simple determination of donor and host contribution to the muscle. FACS analysis of cardiotoxin-damaged muscle revealed that CD45+ bone-marrow side-population (SP) cells, a group enriched in hematopoietic stem cells, can give rise to CD45–/Sca-1+/desmin+ cells capable of myogenic differentiation. Moreover, after immunohistochemical examination of the muscles of both SP- and whole bone marrow-transplanted animals, we noted the presence of myofibers composed only of bone marrow-derived cells. Our findings suggest that a subpopulation of bone marrow SP cells contains precursor cells whose progeny have the potential to differentiate towards a muscle lineage and are capable of de novo myogenesis following transplantation and initiation of muscle repair via chemical damage.

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Normal myoblast injections provide genetic treatment for murine dystrophy

Cited by 114 publications

References 39 publications

Contractile properties of skinned muscle fibres from young and adult normal and dystrophic (mdx) mice.

Contractile properties of skinned muscle fibres from young and adult normal and dystrophic (mdx) mice.

Molecular and functional analysis of the muscle-specific promoter region of the Duchenne muscular dystrophy gene.

Bone marrow side population cells are enriched for progenitors capable of myogenic differentiation

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