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Mol Ther ; 20(11): 2153-67, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22990676

RESUMO

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.


Assuntos
Células-Tronco Embrionárias/fisiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/terapia , Mioblastos Esqueléticos/transplante , Animais , Diferenciação Celular , Fusão Celular , Forma Celular , Células Cultivadas , Meios de Cultura , Distrofina/metabolismo , Células-Tronco Embrionárias/transplante , Humanos , Células-Tronco Pluripotentes Induzidas/transplante , Lamina Tipo A/metabolismo , Camundongos , Camundongos Endogâmicos mdx , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/fisiopatologia , Proteína MyoD/genética , Proteína MyoD/metabolismo , Mioblastos Esqueléticos/metabolismo , Mioblastos Esqueléticos/patologia , Regeneração , Espectrina/metabolismo , Transfecção
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