Duchenne muscular dystrophy (DMD) is an incurable degenerative
muscle disorder. We injected WT mouse induced pluripotent stem cells (iPSCs) into mdx and mdx∶utrophin mutant blastocysts, which are predisposed to develop DMD with an increasing degree of severity (mdx <<< mdx∶utrophin). In mdx chimeras, iPSC-
dystrophin was supplied to the muscle sarcolemma to effect corrections at morphological and functional levels.
Dystrobrevin was observed in
dystrophin-positive and, at a lesser extent,
utrophin-positive areas. In the mdx∶utrophin mutant chimeras, although iPSC-
dystrophin was also supplied to the muscle sarcolemma, mice still displayed poor skeletal muscle histopathology, and negligible levels of
dystrobrevin in
dystrophin- and
utrophin-negative areas. Not only
dystrophin-expressing tissues are affected by iPSCs. Mdx and mdx∶utrophin mice have reduced fat/body weight ratio, but iPSC injection normalized this parameter in both mdx and mdx∶utrophin chimeras, despite the fact that
utrophin was compromised in the mdx∶utrophin chimeric fat. The results suggest that the presence of
utrophin is required for the iPSC-corrections in skeletal muscle. Furthermore, the results highlight a potential (
utrophin-independent) non-cell autonomous role for iPSC-
dystrophin in the corrections of non-muscle tissue like fat, which is intimately related to the muscle.