title: An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells.
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.
authors: Department of Medicine, Lillehei Heart Institute, University of Minnesota, 312 Church Street SE, Minneapolis, Minnesota 55455, USA.
authors: Antonio
authors: A
authors: Filareto
authors: Sarah
authors: S
authors: Parker
authors: Radbod
authors: R
authors: Darabi
authors: Luciene
authors: L
authors: Borges
authors: Michelina
authors: M
authors: Iacovino
authors: Tory
authors: T
authors: Schaaf
authors: Timothy
authors: T
authors: Mayerhofer
authors: Jeffrey S
authors: JS
authors: Chamberlain
authors: James M
authors: JM
authors: Ervasti
authors: R Scott
authors: RS
authors: McIvor
authors: Michael
authors: M
authors: Kyba
authors: Rita C R
authors: RC
authors: Perlingeiro
mesh_terms: D000818:Animals; D002451:Cell Compartmentation; D016189:Dystrophin / Q000378:metabolism; D015316:Genetic Therapy; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D007537:Isometric Contraction; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D020127:Recovery of Function; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000378:metabolism; D049411:Utrophin / Q000235:genetics
chemical_list: D016189:Dystrophin; D049411:Utrophin