Cell Transplantation | |
Radio Electric Conveyed Fields Directly Reprogram Human Dermal Skin Fibroblasts toward Cardiac, Neuronal, and Skeletal Muscle-Like Lineages | |
Article | |
Margherita Maioli1  Sara Santaniello1  Gianfranco Pigliaru1  Sara Gualini1  Carlo Ventura2  Claudia Cavallini2  Salvatore Rinaldi3  Alessandro Castagna3  Vania Fontani3  | |
[1] Department of Biomedical Sciences, University of Sassari, Sassari, Italy;Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Bologna, Italy;Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Bologna, Italy;Cardiovascular Department, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy;Rinaldi Fontani Institute, Florence, Italy; | |
关键词: Direct reprogramming; Human fibroblasts; Radio electric conveyed fields (RECF); | |
DOI : 10.3727/096368912X657297 | |
received in 2011-11-24, accepted in 2012-05-31, 发布年份 2013 | |
来源: Sage Journals | |
【 摘 要 】
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.
【 授权许可】
Unknown
© 2013 Cognizant Comm. Corp.
【 预 览 】
Files | Size | Format | View |
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RO202212203317692ZK.pdf | 340KB | download | |
Figure 3 | 31KB | Image | download |
Figure 5. | 496KB | Image | download |
Figure 14. | 232KB | Image | download |
Figure 6 | 45KB | Image | download |
Figure 7 | 45KB | Image | download |
Figure 1 | 35KB | Image | download |
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