Isolation and Culture of Human Stem Cells from Apical Papilla under Low Oxygen Concentration Highlight Original Properties

Cells. 2019 Nov 21;8(12):1485. doi: 10.3390/cells8121485.


: Stem cells isolated from the apical papilla of wisdom teeth (SCAPs) are an attractive model for tissue repair due to their availability, high proliferation rate and potential to differentiate in vitro towards mesodermal and neurogenic lineages. Adult stem cells, such as SCAPs, develop in stem cell niches in which the oxygen concentration [O2] is low (3-8% compared with 21% of ambient air). In this work, we evaluate the impact of low [O2] on the physiology of SCAPs isolated and processed in parallel at 21% or 3% O2 without any hyperoxic shock in ambient air during the experiment performed at 3% O2. We demonstrate that SCAPs display a higher proliferation capacity at 3% O2 than in ambient air with elevated expression levels of two cell surface antigens: the alpha-6 integrin subunit (CD49f) and the embryonic stem cell marker (SSEA4). We show that the mesodermal differentiation potential of SCAPs is conserved at early passage in both [O2], but is partly lost at late passage and low [O2], conditions in which SCAPs proliferate efficiently without any sign of apoptosis. Unexpectedly, we show that autophagic flux is active in SCAPs irrespective of [O2] and that this process remains high in cells even after prolonged exposure to 3% O2.

Keywords: BNIP3; CD49f; SCAPs; SSEA4; autophagy; differentiation; low oxygen concentration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology
  • Cell Culture Techniques / methods*
  • Cell Differentiation / physiology
  • Cell Hypoxia / physiology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Dental Papilla / metabolism*
  • Humans
  • Integrin alpha6 / metabolism
  • Membrane Proteins / metabolism
  • Molar, Third / cytology
  • Osteogenesis / physiology
  • Oxygen / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Stage-Specific Embryonic Antigens / metabolism
  • Stem Cell Niche / physiology
  • Stem Cells / cytology*


  • BNIP3 protein, human
  • Integrin alpha6
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Stage-Specific Embryonic Antigens
  • stage-specific embryonic antigen-4
  • Oxygen