Reprogramming efficiency and quality of induced Pluripotent Stem Cells (iPSCs) generated from muscle-derived fibroblasts of mdx mice at different ages
- PMID: 22101343
- PMCID: PMC3203521
- DOI: 10.1371/currents.RRN1274
Reprogramming efficiency and quality of induced Pluripotent Stem Cells (iPSCs) generated from muscle-derived fibroblasts of mdx mice at different ages
Abstract
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.
References
-
- Monaco AP, Neve RL, Colletti-Feener C, Bertelson CJ, Kurnit DM, et al. (1986) Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature 323: 646-650. - PubMed
-
- Hoffman EP, Brown RH, Jr., Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51: 919-928. - PubMed
-
- Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663-676. - PubMed
-
- Kazuki, Y., Hiratsuka, M., Takiguchi, M., Osaki, M., Kajitani, N., Hoshiya, H., Hiramatsu, K., Yoshino, T., Kazuki, K., Ishihara, C., Takehara, S., Higaki, K., Nakagawa, M., Takahashi, K., Yamanaka, S., and Oshimura, M. (2010) Complete genetic correction of ips cells from Duchenne muscular dystrophy. Mol Ther 18, 386-393 - PMC - PubMed
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