Muscle to growth stimuli that are not normally present within dystrophic

Muscle to growth stimuli that are not normally present within dystrophic muscle: for example, calcineurin signalling, that mediates muscle hypertrophy [59], is aberrant in mdx muscles, but, if overexpressed, can ameliorate their regeneration [60]. Our findings have some similarities, but also some differences, to previous work that concluded that isolated Solvent Yellow 14 fibres grafted into injured mouse muscle have a hypertrophic effect, but that donorsatellite cells contributed robustly to muscle fibre regeneration [61]. Similar to our findings, Hall et al. found that neither injury, nor myofiber transplantation alone increases muscle mass. In contrast to our findings, they concluded that the increase in muscle mass was donor satellite cell mediated, as they found, again in stark contrast to our findings, that grafted isolated fibres contributed to robust regeneration within injured host muscles. These discrepancies may be explained by differences in experimental procedures between the two studies. In the experiments that Hall et al. performed, single fibres were grafted after 3? hours of incubation in medium containing 15 horse serum at ,6 O2 in the presence of 1.5 nM fibroblast growth factor? for 4 to 5 hours. Isolated fibres were then transferred into 40 ml of 1.2 BaCl2 and fibres were injected in a volume of 70 ml of 1.2 BaCl2 into each host muscle. Hall et al. transplanted 5 donor myofibres per host muscle and used GFP as a marker of muscle and satellite cells of donor origin, whereas we grafted one freshlyisolated fibre per host muscle and used dystrophin and either myosin 3F-nlacZ-2E or b-actin-Cre:R26NZG as markers of either muscle fibres or nuclei of donor origin. Hall et al used nondystrophic, non-immunodeficient host mice (C57Bl/6xDBA2), whereas we used dystrophin deficient, immunodeficient hosts (mdx nude) whose muscles had been injured by injection of 25 ml of 1.2 BaCl2 3 days previously. Our results show that a wild type donor fibre can stimulate the hypertrophic growth of mdx muscle without making any direct contribution to the host muscle tissue. How this happens and from which compartment of the fibre the paracrine signalling originates are questions for future investigation. However, that such a simple procedure -merely grafting an isolated muscle fibre- promotes hypertrophy in a dystrophic muscle could have future therapeutic implications.Author ContributionsConceived and designed the experiments: LB. Performed the experiments: LB. Analyzed the data: LB. Contributed reagents/materials/analysis tools: JEM. Wrote the paper: LB JEM.
The generation of transgenic livestock holds considerable promise for the development of biomedical and agricultural systems [1,2]. The first transgenic livestock was produced via microinjection of foreign DNA into pronuclei of zygote in 1985 [3]. In 1986, cloning sheep was generated by nuclear transfer using embryonic stem cells as donors [4], and then cloning sheep Dolly was born in 1997 by somatic cell cloning (SCC) [5]. BTZ-043 Concomitant with the success of SCC, the first cloning transgenic sheep was produced by nuclear transfer with stably transgenic somatic cells. In spite of the success in generation of transgenic livestock by pronuclear microinjection or SCC, concurrent techniques shows several significant shortcomings, such as low efficiency, high cost, random integration, and frequent incidenceof mosaicism. Efficient generation of transgenic livestock with low cost remains to be developed in transg.Muscle to growth stimuli that are not normally present within dystrophic muscle: for example, calcineurin signalling, that mediates muscle hypertrophy [59], is aberrant in mdx muscles, but, if overexpressed, can ameliorate their regeneration [60]. Our findings have some similarities, but also some differences, to previous work that concluded that isolated fibres grafted into injured mouse muscle have a hypertrophic effect, but that donorsatellite cells contributed robustly to muscle fibre regeneration [61]. Similar to our findings, Hall et al. found that neither injury, nor myofiber transplantation alone increases muscle mass. In contrast to our findings, they concluded that the increase in muscle mass was donor satellite cell mediated, as they found, again in stark contrast to our findings, that grafted isolated fibres contributed to robust regeneration within injured host muscles. These discrepancies may be explained by differences in experimental procedures between the two studies. In the experiments that Hall et al. performed, single fibres were grafted after 3? hours of incubation in medium containing 15 horse serum at ,6 O2 in the presence of 1.5 nM fibroblast growth factor? for 4 to 5 hours. Isolated fibres were then transferred into 40 ml of 1.2 BaCl2 and fibres were injected in a volume of 70 ml of 1.2 BaCl2 into each host muscle. Hall et al. transplanted 5 donor myofibres per host muscle and used GFP as a marker of muscle and satellite cells of donor origin, whereas we grafted one freshlyisolated fibre per host muscle and used dystrophin and either myosin 3F-nlacZ-2E or b-actin-Cre:R26NZG as markers of either muscle fibres or nuclei of donor origin. Hall et al used nondystrophic, non-immunodeficient host mice (C57Bl/6xDBA2), whereas we used dystrophin deficient, immunodeficient hosts (mdx nude) whose muscles had been injured by injection of 25 ml of 1.2 BaCl2 3 days previously. Our results show that a wild type donor fibre can stimulate the hypertrophic growth of mdx muscle without making any direct contribution to the host muscle tissue. How this happens and from which compartment of the fibre the paracrine signalling originates are questions for future investigation. However, that such a simple procedure -merely grafting an isolated muscle fibre- promotes hypertrophy in a dystrophic muscle could have future therapeutic implications.Author ContributionsConceived and designed the experiments: LB. Performed the experiments: LB. Analyzed the data: LB. Contributed reagents/materials/analysis tools: JEM. Wrote the paper: LB JEM.
The generation of transgenic livestock holds considerable promise for the development of biomedical and agricultural systems [1,2]. The first transgenic livestock was produced via microinjection of foreign DNA into pronuclei of zygote in 1985 [3]. In 1986, cloning sheep was generated by nuclear transfer using embryonic stem cells as donors [4], and then cloning sheep Dolly was born in 1997 by somatic cell cloning (SCC) [5]. Concomitant with the success of SCC, the first cloning transgenic sheep was produced by nuclear transfer with stably transgenic somatic cells. In spite of the success in generation of transgenic livestock by pronuclear microinjection or SCC, concurrent techniques shows several significant shortcomings, such as low efficiency, high cost, random integration, and frequent incidenceof mosaicism. Efficient generation of transgenic livestock with low cost remains to be developed in transg.

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