In vivo reprogramming of adult somatic cells to pluripotency by overexpression of yamanaka factors

Açelya Yilmazer, Irene de Lázaro, Cyrill Bussy, Kostas Kostarelos

Research output: Contribution to journalArticlepeer-review


Induced pluripotent stem (iPS) cells that result from the reprogramming of somatic cells to a pluripotent state by forced expression of defined factors are offering new opportunities for regenerative medicine. Such clinical applications of iPS cells have been limited so far, mainly due to the poor efficiency of the existing reprogramming methodologies and the risk of the generated iPS cells to form tumors upon implantation. We hypothesized that the reprogramming of somatic cells towards pluripotency could be achieved in vivo by gene transfer of reprogramming factors. In order to efficiently reprogram cells in vivo, high levels of the Yamanaka (OKSM) transcription factors need to be expressed at the target tissue. This can be achieved by using different viral or nonviral gene vectors depending on the target tissue. In this particular study, hydrodynamic tail-vein (HTV) injection of plasmid DNA was used to deliver the OKSM factors to mouse hepatocytes. This provided proof-of-evidence of in vivo reprogramming of adult, somatic cells towards a pluripotent state with high efficiency and fast kinetics. Furthermore no tumor or teratoma formation was observed in situ. It can be concluded that reprogramming somatic cells in vivo may offer a potential approach to induce enhanced pluripotency rapidly, efficiently, and safely compared to in vitro performed protocols and can be applied to different tissue types in the future.

Original languageEnglish (US)
Article numbere50837
JournalJournal of Visualized Experiments
Issue number82
StatePublished - Dec 17 2013


  • Gene Expression
  • Gene Therapy
  • General
  • Induced Pluripotent Stem Cells (iPSCs)
  • Issue 82
  • OKSM
  • Pluripotent Stem Cells
  • Regenerative medicine
  • Stem Cell Biology
  • Transcription Factors
  • iPS

ASJC Scopus subject areas

  • General Neuroscience
  • General Chemical Engineering
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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