Anti-inflammatory Effects of Oct4/Sox2-overexpressing Human Adipose Tissue-derived Mesenchymal Stem Cells

In Vivo. 2017 May-Jun;31(3):349-356. doi: 10.21873/invivo.11066.

Abstract

Background/aim: The transcription factors Oct4 and Sox2 enhance the proliferation and pluripotency of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs); however, the anti-inflammatory effects of Oct4- and Sox2-overexpressing hAT-MSCs (Oct4/Sox2-hAT-MSCs) are unclear. Here, we evaluated the anti-inflammatory effects of Oct4/Sox2-hAT-MSCs in vitro and in vivo.

Materials and methods: Supernatants from green-fluorescent protein (GFP)- and Oct4/Sox2-hAT-MSCs were used to treat lipopolysaccharide (LPS)-stimulated RAW264.7 cells and inflammatory cytokine expression was determined. In LPS-induced mice, GFP- and Oct4/Sox2-hAT-MSCs were injected intraperitoneally and survival rates, as well as sickness scores of mice, were monitored.

Results: Decreased expression of pro-inflammatory cytokines was observed in Oct4/Sox2-hAT-MSC supernatant-exposed RAW264.7 cells compared to that in GFP-hAT-MSC supernatant-exposed RAW264.7 cells. The sickness score was reduced to 34.9% and the survival rate was increased by 11.1% in Oct4/Sox2-hAT-MSC-injected mice compared to that in GFP-hAT-MSC-injected mice.

Conclusion: Our findings provide important insights into the development of therapies utilizing Oct4/Sox2-hAT-MSCs in inflammatory diseases.

Keywords: Inflammation; Oct4; Sox2; lipopolysaccharide; mesenchymal stem cell.

MeSH terms

  • Adipose Tissue / metabolism*
  • Animals
  • Anti-Inflammatory Agents / metabolism*
  • Cells, Cultured
  • Cytokines / metabolism
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Inflammation / metabolism
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Octamer Transcription Factor-3 / metabolism*
  • RAW 264.7 Cells
  • SOXB1 Transcription Factors / metabolism*
  • Survival Rate

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Green Fluorescent Proteins