Transient in vitro epigenetic reprogramming of skin fibroblasts into multipotent cells

Biomaterials. 2010 Apr;31(10):2779-87. doi: 10.1016/j.biomaterials.2009.12.027. Epub 2009 Dec 30.

Abstract

Multipotent stem cells have the potential to establish a new field of promising regenerative medicine to treat tissue damage, genetic disorders, and degenerative diseases. However, limited resource of stem cells has turned to be an evitable obstacle in clinical applications. We utilized a simple in vitro epigenetic reprogramming approach to convert skin fibroblasts into multipotent cells. After transient reprogramming, stem cell markers, including Oct4 and Nanog, became activated in the treated cells. The reprogrammed cells were multipotent as demonstrated by their ability to differentiate into a variety of cells and to form teratomas. Genomic imprinting of insulin-like growth factor II (Igf2) and H19 was not affected by this short period of cell reprogramming. This study may provide an alternative strategy to efficiently generate patient-specific stem cells for basic and clinical research, solving major hurdles of virally-induced pluripotent stem (iPS) cells that entail the potential risks of mutation, gene instability, and malignancy.

Keywords: Induced multipotent stem cells; differentiation; epigenetic reprogramming; fish oocyte extracts; iMS cells; multipotency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cell Extracts
  • Cell Proliferation
  • Cellular Reprogramming / genetics*
  • Epigenesis, Genetic*
  • Fibroblasts / metabolism*
  • Fishes
  • Genomic Imprinting
  • Humans
  • Insulin-Like Growth Factor II / metabolism
  • Mice
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / metabolism
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Oocytes / cytology
  • Oocytes / metabolism
  • RNA, Long Noncoding
  • RNA, Untranslated / metabolism
  • Skin / cytology*
  • Teratoma / pathology

Substances

  • Biomarkers
  • Cell Extracts
  • H19 long non-coding RNA
  • Octamer Transcription Factor-3
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Insulin-Like Growth Factor II