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First published online September 12, 2003
doi: 10.1242/10.1242/jcs.00721

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

School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, Perth, WA 6009, Australia

View larger version (37K): [in a new window]   Fig. 1. Schematic representation of irradiation regimes. Female host mdx mice were subjected to one of the following regimes: no treatment (control, white mouse), whole body irradiation (WBI, black mouse) (A), WBI plus bone marrow reconstitution (BMR speckled mouse) (B), WBI with single leg excluded (white leg and black body) (C), single leg irradiation (black leg) (D), or NK cell depletion followed by single leg irradiation (NK- and black leg) (E). Myoblast transfer therapy (MTT) was performed 1 hour, 24 hours or 1 week after irradiation, and samples taken up to 24 weeks after injection of cultured donor male myoblasts.

View larger version (23K): [in a new window]   Fig. 2. (A) Number of donor male myoblasts after MTT of untreated (control), whole body irradiated (WBI) and WBI followed 1 hour later by bone marrow reconstitution (BMR) hosts. All mdx host mice are female. MTT was performed 24 hours after WBI and muscles sampled at 1, 24 and 72 hours. Schematics of the irradiation treatment of host mice as described in Fig. 1 are indicated in the top right-hand corner. Bars indicate standard deviation. *P<0.05 and **P<0.005 (untreated to treated samples) using ANOVA; d and dd indicates significance of P<0.05 or P<0.005, respectively, between treatment groups at each time point using ANOVA; n=6 unless otherwise stated. (B) Number of donor male myoblasts after MTT of untreated (control), WBI and WBI/BMR, female mdx host mice. MTT was performed 1 hour after BMR and muscles sampled at 1 hour, 24 hours, 1, 3, 12 and 24 weeks after MTT. Bars indicate s.d. *P<0.05, **P<0.005 (untreated to treated samples) using ANOVA; d and dd indicate significances of P<0.05 or P<0.005, respectively, between treatment groups at each time point using ANOVA (n=6 unless otherwise stated).

View larger version (23K): [in a new window]   Fig. 3. (A) Numbers of donor myoblasts in irradiated and contralateral (protected) TA muscles in mdx host mice subjected to WBI with one leg protected. MTT was performed 24 hours after WBI and muscles sampled at 1 hour, 24 hours and 72 hours after MTT. Schematics of the irradiation treatment of host mice (see Fig. 1) are indicated in the top right-hand corner. Bars indicate s.d. * P<0.05, **P<0.005 (untreated to treated samples) using ANOVA; d and dd indicate significances of P<0.05 or P<0.005, respectively, between treatment groups at each time point using ANOVA (n=6 unless otherwise stated). (B) Numbers of donor myoblasts in irradiated and contralateral (protected) TA muscles in mdx host mice subjected to local irradiation of one leg only. MTT was performed 24 hours after irradiation and muscles sampled at 1 hour, 24 hours and 72 hours after MTT. Bars indicate s.d. *P<0.05, **P<0.005 (untreated to treated samples) using ANOVA; d and dd indicate significances of P<0.05 or P<0.005, respectively, between treatment groups at each time point using ANOVA (n=6 unless otherwise stated).

View larger version (22K): [in a new window]   Fig. 4. Numbers of donor myoblasts in locally irradiated and contralateral (protected) TA muscles in mdx host mice subjected to local irradiation of one leg. MTT was performed at 1 hour (A) or 1 week (B) after irradiation and muscles sampled at 24 hours, 1 week, 3 weeks, 12 weeks and 24 weeks after MTT. Schematics of the irradiation treatment of host mice (see Fig. 1) are indicated in the top right hand corner. Bars indicate standard deviation. * and ** indicates significance of P<0.05 or P<0.005, respectively, between untreated and treated samples using ANOVA; d and dd indicates significance of P<0.05 or P<0.005, respectively, between treatment groups at each time point using ANOVA, n=6 unless otherwise stated.

View larger version (26K): [in a new window]   Fig. 5. Numbers of donor myoblasts in irradiated and contralateral (protected) TA muscles in NK-depleted mdx host mice where MTT was performed at 1 hour after local irradiation and muscles sampled at 1 hour, 24 hours, 1 week, 3 weeks, 12 weeks and 24 weeks after MTT. Schematics of the irradiation treatment of host mice (see Fig. 1) are indicated in the top right hand corner. Bars indicate s.d. *P<0.05, **P<0.005 (untreated to treated samples) using ANOVA; d and dd indicate significances of P<0.05 or P<0.005, respectively, between treatment groups at each time point using ANOVA (n=6 unless otherwise stated).

View larger version (29K): [in a new window]   Fig. 6. Profiles of circulating cytokines TNF, IL-1ß, IL-6 and IL-12 in sera from mdx host mice subjected to WBI and WBI/BMR (A-D), local irradiation (single leg) followed by MTT 1 hour or 1 week later (E-H), or NK depletion with or without local irradiation of a single leg (IL). Levels of cytokines are expressed as a percentage of that detected in untreated control mdx (no MTT) and shown at various times after MTT. The scale for the amounts of cytokines changes between the data sets. Samples represent the value of pooled sera from four mice at each time point.