1. Radio electric conveyed fields directly reprogram human dermal skin fibroblasts toward cardiac, neuronal, and skeletal muscle-like lineages.
- Author
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Maioli M, Rinaldi S, Santaniello S, Castagna A, Pigliaru G, Gualini S, Cavallini C, Fontani V, and Ventura C
- Subjects
- Cell Differentiation, Cell Lineage, Cells, Cultured, Cellular Reprogramming, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Humans, Kruppel-Like Factor 4, Muscle Development physiology, MyoD Protein genetics, MyoD Protein metabolism, NADPH Oxidases genetics, NADPH Oxidases metabolism, Neurogenesis, Proto-Oncogene Proteins c-myc genetics, Proto-Oncogene Proteins c-myc metabolism, Reactive Oxygen Species metabolism, Transcription Factors genetics, Transcription Factors metabolism, Dermis cytology, Fibroblasts cytology, Muscle, Skeletal cytology, Myocardium cytology, Neurons cytology, Radio Waves
- Abstract
Somatic cells can be directly reprogrammed to alternative differentiated fates without first becoming stem/progenitor cells. Nevertheless, the initial need for viral-mediated gene delivery renders this strategy unsafe in humans. Here, we provide evidence that exposure of human skin fibroblasts to a Radio Electric Asymmetric Conveyer (REAC), an innovative device delivering radio electric conveyed fields at a radiofrequency of 2.4 GHz, afforded remarkable commitment toward cardiac, neuronal, and skeletal muscle lineages. REAC induced the transcription of tissue-restricted genes, including Mef2c, Tbx5, GATA4, Nkx2.5, and prodynorphin for cardiac reprogramming, as well as myoD, and neurogenin 1 for skeletal myogenesis and neurogenesis, respectively. Conversely, REAC treatment elicited a biphasic effect on a number of stemness-related genes, leading to early transcriptional increase of Oct4, Sox2, cMyc, Nanog, and Klf4 within 6-20 h, followed by a downregulation at later times. The REAC action bypassed a persistent reprogramming toward an induced pluripotent stem cell-like state and involved the transcriptional induction of the NADPH oxidase subunit Nox4. Our results show for the first time the feasibility of using a physical stimulus to afford the expression of pluripotentiality in human adult somatic cells up to the attainment of three major target lineages for regenerative medicine. more...
- Published
- 2013
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