Duchenne muscular dystrophy is a progressive and incurable neuromuscular disease caused by genetic and biochemical defects of the dystrophin–glycoprotein complex. Here, the authors show the regenerative potential of myogenic progenitors derived from corrected dystrophic induced pluripotent stem cells generated from fibroblasts of mice lacking both dystrophin and utrophin. The phenotype of dystrophic induced pluripotent stem cells was corrected using a Sleeping Beauty transposon system carrying the micro-utrophin gene, these cells were then differentiated into skeletal muscle progenitors and transplanted back into dystrophic mice. Engrafted muscles displayed large numbers of micro-utrophin-positive myofibers, with biochemically restored dystrophin–glycoprotein complex and improved contractile strength. The transplanted cells seed the satellite cell compartment, responded properly to injury and exhibit neuromuscular synapses. Muscle engraftment after systemic delivery of these corrected progenitors was also detected. These results represent an important advance towards the future treatment of muscular dystrophies using genetically corrected autologous induced pluripotent stem cells.
