Introduction: Residual pluripotent stem cells (PSC) within differentiated populations are problematic because of their potential to form tumors. Simple methods to reduce their occurrence are needed. Methods: Here, we demonstrate that control of the oxygen partial pressure (pO2) to physiological levels typical of the developing embryo, enabled by culture on a highly oxygen permeable substrate, reduces the fraction of PSC within and the tumorigenic potential of differentiated populations. Results: Differentiation and/or extended culture at low pO2 reduced measured pluripotency markers by up to four orders of magnitude for mouse PSCs (mPSCs). Combination with cell sorting increased the reduction to as much as six orders of magnitude. Upon implantation into immunocompromised mice, mPSCs differentiated at low pO2 either did not form tumors or formed tumors at a slower rate than at high pO2. Conclusions: Low pO2 culture alone or in combination with other methods is a potentially straightforward method that could be applied to future cell therapy protocols to minimize the possibility of tumor formation.

Original languageEnglish
Pages (from-to)555-567
Number of pages13
JournalCellular and Molecular Bioengineering
Issue number6
StatePublished - Dec 2021


  • Cell therapy
  • Differentiation
  • Hypoxia
  • Oxygen
  • Pluripotent stem cells
  • Teratoma
  • Transplantation


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