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Generation of Induced Pluripotent Stem Cells by Reprogramming Human Fibroblasts with the Stemgent Human TF Lentivirus Set
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Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2

Danwei Huangfu1, Kenji Osafune, René Maehr

  • 1Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.

Nature Biotechnology
|October 14, 2008
PubMed

Insights

Valproic acid (VPA) enables reprogramming of human fibroblasts into induced pluripotent stem (iPS) cells using only Oct4 and Sox2. This chemical reprogramming method avoids oncogenes, enhancing safety for therapeutic applications.

Area of Science:

  • Stem cell biology
  • Epigenetics
  • Molecular medicine

Background:

  • Somatic cell reprogramming to induced pluripotent stem (iPS) cells is crucial for regenerative medicine.
  • Current methods often rely on viral transgenes, including oncogenes like c-Myc and Klf4, limiting therapeutic potential due to safety concerns.
  • Low reprogramming efficiency hinders mechanistic studies and clinical translation.

Purpose of the Study:

  • To investigate if chemical modifiers can improve reprogramming efficiency and safety.
  • To develop a method for generating human iPS cells using fewer factors and avoiding oncogenes.
  • To assess the pluripotency and characteristics of chemically induced iPS cells.

Main Methods:

  • Utilized valproic acid (VPA), a histone deacetylase inhibitor, as a chemical reprogramming enhancer.
  • Employed only two reprogramming factors: Oct4 and Sox2, omitting c-Myc and Klf4.
  • Derived and characterized induced pluripotent stem cells from primary human fibroblasts.

Main Results:

  • Valproic acid (VPA) enabled efficient reprogramming of human fibroblasts with only Oct4 and Sox2.
  • The generated two-factor induced iPS cells exhibited pluripotency comparable to embryonic stem (ES) cells.
  • Global gene expression and epigenetic profiles of these iPS cells mirrored those of human ES cells.
  • The method successfully avoided the use of oncogenes c-Myc and Klf4.

Conclusions:

  • Histone deacetylase inhibition with VPA facilitates safer and more efficient reprogramming.
  • Reprogramming with Oct4 and Sox2, enhanced by VPA, offers a promising alternative for generating clinical-grade iPS cells.
  • Chemical reprogramming holds potential for safer and more practical therapeutic applications of stem cells.

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