Generation of feeder-free pig induced pluripotent stem cells without Pou5f1

Nuria Montserrat, Lorena de Oñate, Elena Garreta, Federico González, Antonio Adamo, Cristina Eguizábal, Sophia Häfner, Rita Vassena, Juan Carlos Izpisua Belmonte

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The pig represents an ideal large-animal model, intermediate between rodents and humans, for the preclinical assessment of emerging cell therapies. As no validated pig embryonic stem (pES) cell lines have been derived so far, pig induced pluripotent stem cells (piPSCs) should offer an alternative source of undifferentiated cells to advance regenerative medicine research from bench to clinical trial. We report here for the first time the derivation of piPSCs from adult fibroblast with only three transcription factors: Sox2 (sex determining region Y-box 2), Klf4 (Kruppel-like factor 4), and c-Myc (avian myelocytomatosis viral oncogene homolog). We have been able to demonstrate that exogenous Pou5f1 (POU domain class 5 transcription factor 1; abbreviated as Octamer-4: Oct4) is dispensable to achieve and maintain pluripotency in the generation of piPSCs. To the best of our knowledge, this is also the first report of somatic reprogramming in any species without the overexpression, either directly or indirectly, of Oct4. Moreover, we were able to generate piPSCs without the use of feeder cells, approaching thus xeno-free conditions. Our work paves the way for the derivation of clinical grade piPSCs for regenerative medicine.

Original languageEnglish (US)
Pages (from-to)815-825
Number of pages11
JournalCell Transplantation
Volume21
Issue number5
DOIs
StatePublished - Jun 25 2012
Externally publishedYes

Keywords

  • Cell culture
  • Clinical translation
  • Embryonic stem cells (ESCs)
  • Induced pluripotent stem (iPS) cells

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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