Hypoxia-enhanced derivation of iPSCs from human dental pulp cells

J Dent Res. 2013 Oct;92(10):905-10. doi: 10.1177/0022034513502204. Epub 2013 Aug 20.


Hypoxia enhances the reprogramming efficiency of human dermal fibroblasts to become induced pluripotent stem cells (iPSCs). Because we showed previously that hypoxia facilitates the isolation and maintenance of human dental pulp cells (DPCs), we examined here whether it promotes the reprogramming of DPCs to become iPSCs. Unlike dermal fibroblasts, early and transient hypoxia (3% O2) induced the transition of DPCs to iPSCs by 3.3- to 5.1-fold compared with normoxia (21% O2). The resulting iPSCs closely resembled embryonic stem cells as well as iPSCs generated in normoxia, as judged by morphology and expression of stem cell markers. However, sustained hypoxia strongly inhibited the appearance of iPSC colonies and altered their morphology, and anti-oxidants failed to suppress this effect. Transient hypoxia increased the expression levels of NANOG and CDH1 and modulated the expression of numerous genes, including those encoding chemokines and their receptors. Therefore, we conclude that hypoxia, when optimized for cell type, is a simple and useful tool to enhance the reprogramming of somatic cells to become iPSCs.

Keywords: cadherins; cell hypoxia; chemokines; microarray analysis; odontoblasts; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD
  • Antioxidants / pharmacology
  • Cadherins / biosynthesis
  • Cadherins / genetics*
  • Cell Hypoxia / genetics*
  • Cells, Cultured
  • Cellular Reprogramming
  • Dental Pulp / cytology*
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics*
  • Humans
  • Induced Pluripotent Stem Cells*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanog Homeobox Protein
  • Odontoblasts / cytology
  • Oligonucleotide Array Sequence Analysis / methods


  • Antigens, CD
  • Antioxidants
  • CDH1 protein, human
  • Cadherins
  • Homeodomain Proteins
  • NANOG protein, human
  • Nanog Homeobox Protein