Myoblasts Derived From Normal hESCs and Dystrophic hiPSCs Efficiently Fuse With Existing Muscle Fibers Following Transplantation |
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Authors: | Sébastien Goudenege Carl Lebel Nicolas B Huot Christine Dufour Isao Fujii Jean Gekas Joël Rousseau Jacques P Tremblay |
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Institution: | 1. Unité de recherche de recherche en Génétique Humaine, Centre de recherche de CHUL, CHUQ, Faculté de médecine, Université Laval, Québec, Québec, Canada;2. Laboratory of Clinical Pharmacology and Therapeutics, Department of Pharmaceutical Sciences, Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan;3. Centre de Recherche du Centre Hospitalier Universitaire de Québec (CHUQ), The APOGEE-Net/CanGeneTest Research and Knowledge Network in Genetic Health Services and Policy, Service de Génétique Médicale, Département de Pédiatrie, Faculté de Médecine, Université Laval, Québec, Québec, Canada;4. Centre de Recherche du Centre Hospitalier Universitaire de Québec (CHUQ), The APOGEE-Net/CanGeneTest Research and Knowledge Network in Genetic Health Services and Policy, Service de Génétique Médicale, Département de biologie médicale, Faculté de Médecine, Université Laval, Québec, Québec, Canada |
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Abstract: | Human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) have an endless self-renewal capacity and can theoretically differentiate into all types of lineages. They thus represent an unlimited source of cells for therapies of regenerative diseases, such as Duchenne muscular dystrophy (DMD), and for tissue repair in specific medical fields. However, at the moment, the low number of efficient specific lineage differentiation protocols compromises their use in regenerative medicine. We developed a two-step procedure to differentiate hESCs and dystrophic hiPSCs in myogenic cells. The first step was a culture in a myogenic medium and the second step an infection with an adenovirus expressing the myogenic master gene MyoD. Following infection, the cells expressed several myogenic markers and formed abundant multinucleated myotubes in vitro. When transplanted in the muscle of Rag/mdx mice, these cells participated in muscle regeneration by fusing very well with existing muscle fibers. Our findings provide an effective method that will permit to use hESCs or hiPSCs for preclinical studies in muscle repair. |
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