Abstract
The overexpression of cell reprogramming factors (Oct4, Sox2, Klf4, Nanog, and c-Myc) allows differentiated cells to revertto an earlier developmental stage. Differentiated cells can also be reprogrammed by directly delivering reprogramming proteins tagged with cell-penetrating peptides, which allow the proteins to pass through the cell membrane and into the cytoplasm-although this method has been an inefficient process. Here, we describe a novel technique for delivering reprogramming proteins into cells using titanium oxide (TiO2 ) nanotubes, which show no cytotoxic effects and do not affect cell proliferation. TiO2 nanotubes successfully transferred the above-mentioned reprogramming factors into differentiated somatic cells. After 3 weeks of treatment with protein-conjugated nanotubes, the somatic cells adopted an embryonic stem cell-like morphology and expressed activated Oct4-green fluorescent protein, a pluripotency biomarker. Our results indicate that TiO2 nanotubes can be used to directly deliver reprogramming factors into somatic cells to induce pluripotency.
© 2013 Wiley Periodicals, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Dedifferentiation / genetics
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Cell Differentiation / genetics
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Cell Proliferation
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Cells, Cultured
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Cellular Reprogramming / genetics*
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Embryonic Stem Cells
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Green Fluorescent Proteins / biosynthesis
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Green Fluorescent Proteins / genetics
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Homeodomain Proteins / biosynthesis
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Induced Pluripotent Stem Cells / cytology*
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Kruppel-Like Factor 4
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Kruppel-Like Transcription Factors / biosynthesis
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Metal Nanoparticles
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Mice
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Mice, Transgenic
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Nanog Homeobox Protein
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Nanotubes*
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Octamer Transcription Factor-3 / biosynthesis
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Octamer Transcription Factor-3 / genetics
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Protein Transport / genetics*
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Proto-Oncogene Proteins c-myc / biosynthesis
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SOXB1 Transcription Factors / biosynthesis
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Titanium / pharmacology*
Substances
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Homeodomain Proteins
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Klf4 protein, mouse
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Kruppel-Like Factor 4
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Kruppel-Like Transcription Factors
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Myc protein, mouse
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Nanog Homeobox Protein
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Nanog protein, mouse
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Octamer Transcription Factor-3
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Pou5f1 protein, mouse
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Proto-Oncogene Proteins c-myc
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SOXB1 Transcription Factors
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Sox2 protein, mouse
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Green Fluorescent Proteins
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titanium dioxide
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Titanium