Major Alteration of the Pathological Phenotype in Gamma Irradiated mdx Soleus Muscles

Weller, Boaz; Karpati, George; Lehnert, Shirley; Carpenter, Stirling

doi:10.1097/00005072-199107000-00003

Cited by 28 publications

(26 citation statements)

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“…Irradiation of mdx muscle incapacitates endogenous satellite cells, as a result, the muscle shows few signs of spontaneous regeneration 19,25 and when cultured the vast majority of myofibres fail to produce myogenic cells. 24,26 However, a few myofibres prepared from pre-irradiated mdx nu/nu TA muscles that had been injected with Myf5 nlacZ/+ -derived myoblasts, produced ␤-galactosidaselabelled myogenic cells in culture.…”

Section: Discussionmentioning

confidence: 99%

“…Irradiation of mdx muscle with 18 Gy incapacitates endogenous satellite cells resulting in muscle that shows few signs of regeneration. 19,25 Furthermore, myoblast transplantation is more successful following pre-irradiation of host muscle, compared with non-irradiated muscle, and we therefore adopted this strategy to maximise donor-derived cell incorporation. 20 Finally, using mdx on a nude (nu/nu) background prevents immunological rejection of transplanted cells.…”

Section: Discussionmentioning

confidence: 99%

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Transplanted primary neonatal myoblasts can give rise to functional satellite cells as identified using the Myf5nlacZl+ mouse

et al. 2001

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Myoblast transplantation is a potential therapeutic approach for the genetic modification of host skeletal muscle tissue. To be considered an effective, long-lived method of delivery, however, it is essential that at least a proportion of the transplanted cells also retain their proliferative potential. We sought to investigate whether transplanted neonatal myoblasts can contribute to the satellite cell compartment of adult skeletal muscle by using the Myf5 nlacZ/+ mouse. The Myf5 nlacZ/+ mouse has nlacZ targeted to the Myf5 locus resulting in ␤-galactosidase activity in quiescent satellite cells. Following transplantation, ␤-galactosidase-labelled nuclei were detected in host muscles, showing that donor

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transplanted primary neonatal myoblasts can give rise to functional satellite cells as identified using the Myf5nlacZl+ mouse

et al. 2001

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“…of gamma irradiation inhibit regeneration of the dystrophic muscle from endogenous myoblasts, resulting in mdx muscles more closely resembling the pathology of DMD Quinlan et al, 1997;Quinlan et al, 1995;Wakeford et al, 1991;Weller et al, 1991). Postmitotic (mature) skeletal muscle fibres are not particularly sensitive to radiation and will remain viable unless doses are very high Pagel and Partridge, 1999;Quinlan et al, 1997;Quinlan et al, 1995;Wakeford et al, 1991;Weller et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

“…Postmitotic (mature) skeletal muscle fibres are not particularly sensitive to radiation and will remain viable unless doses are very high Pagel and Partridge, 1999;Quinlan et al, 1997;Quinlan et al, 1995;Wakeford et al, 1991;Weller et al, 1991). Satellite cells, which are the main source of myoblasts in mature muscle, are located outside the myofibre between the basal lamina and plasmalemma of muscle fibres.…”

Section: Introductionmentioning

confidence: 99%

“…below 12 Gy) of irradiation (Ben-Dov et al, 1999;Quinlan et al, 1995). Gamma irradiation has been successfully used to disable the proliferation of myoblasts in skeletal muscle, with little or no apparent damage to the mature muscle fibre, in studies of muscle regeneration (Mitchell et al, 1995;Morgan et al, 1990;Pagel and Partridge, 1999;Quinlan et al, 1997;Quinlan et al, 1995;Robertson et al, 1992;Wakeford et al, 1991;Weller et al, 1991;Wirtz et al, 1982), hypertrophy (Barton-Davis et al, 1999;Phelan and Gonyea, 1997;Rosenblatt and Parry, 1992) and satellite cell activation (Ben-Dov et al, 1999;Gulati, 1987;Lowe and Alway, 1999). Local irradiation of host skeletal muscle (to prevent endogenous regeneration) has also been used as a pretreatment for MTT (Alameddine et al, 1994;Beauchamp et al, 1999;Huard et al, 1994;Kinoshita et al, 1994;Morgan et al, 1996;Morgan et al, 2002;Morgan et al, 1990;Morgan et al, 1993;Wernig et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Irradiation of dystrophic host tissue prior to myoblast transfer therapy enhances initial (but not long-term) survival of donor myoblasts

Hodgetts

Grounds

2003

Journal of Cell Science

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There is a massive and rapid death of donor myoblasts (<20% surviving) within hours after intramuscular injection in myoblast transfer therapy (MTT), due to host immune cells, especially natural killer (NK) cells. To investigate the role of host immune cells in the dramatic death of donor myoblasts, MTT experiments were performed in irradiated host mice. Cultured normal C57BL/10ScSn male donor myoblasts were injected into muscles of female C57BL/10ScSn-Dmdmdx host mice after one of three treatments: whole body irradiation (WBI) to eliminate all circulating leukocytes, WBI and bone marrow reconstitution (BMR), or local irradiation (or protection) of one limb. Similar experiments were performed in host mice after antibody depletion of NK cells. Numbers of male donor myoblasts were quantified using a Y-chromosome-specific (male) probe following total DNA extraction of injected muscles. WBI prior to MTT resulted in dramatically enhanced survival (∼80%) of donor myoblasts at 1 hour after MTT, supporting a central role for host inflammatory cells in the initial death of donor myoblasts seen in untreated host mice. BMR restored the massive and rapid loss (∼25% surviving) of donor myoblasts at 1 hour after MTT. Local pre-irradiation also resulted in increased donor myoblast numbers (∼35-40%) compared with untreated controls (∼10%) at 3 weeks after MTT. Preirradiation of host muscle with 10 Gy did not significantly stimulate proliferation of the injected donor myoblasts. Serum protein levels of TNFα, IL-1β, IL-6 and IL-12 fluctuated following irradiation treatments. These combined results strongly reinforce a major role for host immune cells in the rapid death of injected cultured donor myoblasts.

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Patterns of repair of dystrophic mouse muscle: Studies on isolated fibers

et al. 1999

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Major Alteration of the Pathological Phenotype in Gamma Irradiated mdx Soleus Muscles

Cited by 28 publications

References 0 publications

Transplanted primary neonatal myoblasts can give rise to functional satellite cells as identified using the Myf5nlacZl+ mouse

Transplanted primary neonatal myoblasts can give rise to functional satellite cells as identified using the Myf5nlacZl+ mouse

Irradiation of dystrophic host tissue prior to myoblast transfer therapy enhances initial (but not long-term) survival of donor myoblasts

Patterns of repair of dystrophic mouse muscle: Studies on isolated fibers

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