Radio electric conveyed fields directly reprogram human dermal skin fibroblasts toward cardiac, neuronal, and skeletal muscle-like lineages

Cell Transplant. 2013;22(7):1227-35. doi: 10.3727/096368912X657297. Epub 2012 Oct 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Cellular Reprogramming
  • Dermis / cytology*
  • Fibroblasts / cytology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Kruppel-Like Factor 4
  • Muscle Development / physiology
  • Muscle, Skeletal / cytology*
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Myocardium / cytology*
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Neurogenesis
  • Neurons / cytology*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Radio Waves*
  • Reactive Oxygen Species / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Homeodomain Proteins
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • MyoD Protein
  • Proto-Oncogene Proteins c-myc
  • Reactive Oxygen Species
  • Transcription Factors
  • NADPH Oxidases