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An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells

Author

Listed:
  • Antonio Filareto

    (Lillehei Heart Institute, University of Minnesota)

  • Sarah Parker

    (Lillehei Heart Institute, University of Minnesota)

  • Radbod Darabi

    (Lillehei Heart Institute, University of Minnesota)

  • Luciene Borges

    (Lillehei Heart Institute, University of Minnesota)

  • Michelina Iacovino

    (Lillehei Heart Institute, University of Minnesota)

  • Tory Schaaf

    (Lillehei Heart Institute, University of Minnesota)

  • Timothy Mayerhofer

    (Lillehei Heart Institute, University of Minnesota)

  • Jeffrey S. Chamberlain

    (University of Washington School of Medicine, K243b HSB, Box 357720, 1959 N.E. Pacific Street, Seattle, Washington 98195-7720, USA)

  • James M. Ervasti

    (Molecular Biology and Biophysics, University of Minnesota)

  • R. Scott McIvor

    (Cell Biology and Development, University of Minnesota)

  • Michael Kyba

    (Lillehei Heart Institute, University of Minnesota)

  • Rita C. R. Perlingeiro

    (Lillehei Heart Institute, University of Minnesota)

Abstract

Duchenne muscular dystrophy is a progressive and incurable neuromuscular disease caused by genetic and biochemical defects of the dystrophin–glycoprotein complex. Here we 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. We correct the phenotype of dystrophic induced pluripotent stem cells using a Sleeping Beauty transposon system carrying the micro-utrophin gene, differentiate these cells into skeletal muscle progenitors and transplant them 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. We also detect muscle engraftment after systemic delivery of these corrected progenitors. These results represent an important advance towards the future treatment of muscular dystrophies using genetically corrected autologous induced pluripotent stem cells.

Suggested Citation

  • Antonio Filareto & Sarah Parker & Radbod Darabi & Luciene Borges & Michelina Iacovino & Tory Schaaf & Timothy Mayerhofer & Jeffrey S. Chamberlain & James M. Ervasti & R. Scott McIvor & Michael Kyba & , 2013. "An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells," Nature Communications, Nature, vol. 4(1), pages 1-9, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2550
    DOI: 10.1038/ncomms2550
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