Reprogramming efficiency and quality of induced Pluripotent Stem Cells (iPSCs) generated from muscle-derived fibroblasts of mdx mice at different ages

Induced pluripotent stem cells (iPSCs) hold promise as a potential treatment for Duchenne muscular dystrophy (DMD). To determine the impact of the donor’s age on reprogramming, we generated iPSCs from muscle-derived fibroblasts (MuFs) of mdx mice aged 6 weeks, 6 months, and 14 months. MuFs from 14-m...

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Detalles Bibliográficos
Autores principales: Wang, Bo, Miyagoe-Suzuki, Yuko, Yada, Erica, Ito, Naoki, Nishiyama, Takashi, Nakamura, Miho, Ono, Yusuke, Motohashi, Norio, Segawa, Makoto, Masuda, Satoru, Takeda, Shin'ichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Muscular Dystrophy
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203521/
https://www.ncbi.nlm.nih.gov/pubmed/22101343
http://dx.doi.org/10.1371/currents.RRN1274
Descripción
Sumario:Induced pluripotent stem cells (iPSCs) hold promise as a potential treatment for Duchenne muscular dystrophy (DMD). To determine the impact of the donor’s age on reprogramming, we generated iPSCs from muscle-derived fibroblasts (MuFs) of mdx mice aged 6 weeks, 6 months, and 14 months. MuFs from 14-month-old mdx mice showed lower proliferative activity and lower reprogramming efficiency, compared with those from younger mdx mice. Furthermore, iPSCs derived from 14-month-old mdx mice (14m-MuF-iPSCs) gradually lost Nanog expression, and regressed in conventional ES medium during passages. Interestingly, inhibition of TGF-β signaling and BMP signaling stabilized Nanog expression and promoted self-renewal of 14m-MuF-iPSCs. Finally, rescued mdx-derived iPSCs efficiently differentiated into the skeletal muscle lineage.

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