title: Pluripotent Stem Cells for Gene Therapy of Degenerative Muscle Diseases.
abstract: Human pluripotent stem cells represent a unique source for cell-based therapies and regenerative medicine. The intrinsic features of these cells such as their easy accessibility and their capacity to be expanded indefinitely overcome some limitations of conventional adult stem cells. Furthermore, the possibility to derive patient-specific induced pluripotent stem (iPS) cells in combination with the current development of gene modification methods could be used for autologous cell therapies of some genetic diseases. In particular, muscular dystrophies are considered to be a good candidate due to the lack of efficacious therapeutic treatments for patients to date, and in view of the encouraging results arising from recent preclinical studies. Some hurdles, including possible genetic instability and their efficient differentiation into muscle progenitors through vector/transgene-free methods have still to be overcome or need further optimization. Additionally, engraftment and functional contribution to muscle regeneration in pre-clinical models need to be carefully assessed before clinical translation. This review offers a summary of the advanced methods recently developed to derive muscle progenitors from pluripotent stem cells, as well as gene therapy by gene addition and gene editing methods using ZFNs, TALENs or CRISPR/Cas9. We have also discussed the main issues that need to be addressed for successful clinical translation of genetically corrected patient-specific pluripotent stem cells in autologous transplantation trials for skeletal muscle disorders.
authors.forename: Mariana
authors.initials: M
authors.lastname: Loperfido
authors.forename: Heather B
authors.initials: HB
authors.lastname: Steele-Stallard
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Tedesco
authors.affiliation: Department of Cardiovascular Sciences, University of Leuven, Leuven, 3000, Belgium and Department of Cell and Developmental Biology, University College London, London, WC1E 6DE, United Kingdom. Thierry.Vandendriessche@vub.ac.be.
authors.forename: Thierry
authors.initials: T
authors.lastname: VandenDriessche
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology / Q000637:transplantation; D000818:Animals; D002454:Cell Differentiation; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D009135:Muscular Diseases / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D017570:MyoD Protein / Q000235:genetics; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000502:physiology* / Q000637:transplantation; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods
chemical_list: D017570:MyoD Protein; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; C497322:Pax7 protein, mouse; C068686:Pax3 protein, mouse