Enhanced migration and fusion of donor myoblasts in dystrophic and normal host muscle

Sliced male C57BI/10Sn (H2-b) donor muscles were grafted into the female hi stocompatible muscles of untreated, FK506-treated, and T-cell depleted (wit h or without thymic tolerization) dystrophic (mdx; H2-b) and normal (C57BI/ 10Sn; H2-b) hosts, and also into histoincompatible normal (Balb/c; H2-d) ho sts. The fate of male donor nuclei was monitored on tissue sections by in s itu hybridization with a Y-chromosome specific probe. The results demonstra te that the dystrophic environment is more conducive than normal muscle to donor myoblast migration, with the distance moved being threefold greater a t 12 weeks in dystrophic hosts. T-cell depletion was significantly more eff ective than FK506 treatment at enhancing donor myoblast emigration in both histocompatible and histoincompatible hosts at 3 weeks. Furthermore, the ef fects of T-cell depletion were sustained in histoincompatible hosts at 12 w eeks. These data endorse the use of host T-cell depletion as a promising lo ng-term strategy to improve myoblast transfer therapy (MTT) in the clinical situation. (C) 2000 John Wiley & Sons, Inc.