Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential

M. G. Valorani, A. Germani, W. R. Otto, L. Harper, A. Biddle, C. P. Khoo, W. R. Lin, M. I. Hawa, P. Tropel, M. P. Patrizi, P. Pozzilli, M. R. Alison

Research output: Contribution to journalArticlepeer-review


Mesenchymal stem cells (MSCs) are usually cultured under normoxic conditions (21% oxygen). However, in vivo, the physiological "niches" for MSCs have a much lower oxygen tension. Because of their plasticity, stem cells are particularly sensitive to their environments, and oxygen tension is one developmentally important stimulus in stem cell biology and plays a role in the intricate balance between cellular proliferation and commitment towards differentiation. Therefore, we investigated here the effect of hypoxia (2% oxygen) on murine adipose tissue (AT) MSC proliferation and adipogenic differentiation. AT cells were obtained from the omental fat and AT-MSCs were selected for their ability to attach to the plastic dishes, and were grown under normoxic and hypoxic conditions. Prior exposure of MSCs to hypoxia led to a significant reduction of ex vivo expansion time, with significantly increased numbers of Sca-1+ as well as Sca-1+/CD44 +double-positive cells. Under low oxygen culture conditions, the AT-MSC number markedly increased and their adipogenic differentiation potential was reduced. Notably, the hypoxia-mediated inhibition of adipogenic differentiation was reversible: AT-MSCs pre-exposed to hypoxia when switched to normoxic conditions exhibited significantly higher adipogenic differentiation capacity compared to their pre-exposed normoxic-cultured counterparts. Accordingly, the expression of adipocyte-specific genes, peroxisome proliferator activated receptor γ (Pparγ), lipoprotein lipase (Lpl) and fatty acid binding protein 4 (Fabp4) were significantly enhanced in hypoxia pre-exposed AT-MSCs. In conclusion, pre-culturing MSCs under hypoxic culture conditions may represent a strategy to enhance MSC production, enrichment and adipogenic differentiation.

Original languageEnglish
Pages (from-to)111-120
Number of pages10
JournalCell & Tissue Research
Issue number1
Publication statusPublished - Jul 2010


  • Adipose Tissue
  • CD44
  • Cell culture (Mouse)
  • Differentiation
  • Hypoxia
  • mMSCs
  • Sca-1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Histology
  • Medicine(all)


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