IFN-γ induces senescence-like characteristics in mouse bone marrow mesenchymal stem cells

Adv Clin Exp Med. 2017 Mar-Apr;26(2):201-206. doi: 10.17219/acem/61431.

Abstract

Background: Mesenchymal stem cells (MSC) are considered promising in tissue repair and regeneration medicine due to their proliferation and differentiation ability. Many properties of MSC are affected by cytokines, and IFN-γ has been shown to regulate MSC in many aspects. Senescence affects the proliferation, differentiation and cytokine secretion of MSC.

Objectives: To investigate the effects of IFN-γ on the senescence-associated properties of MSC.

Material and methods: The MSC used in our study were isolated from the bone marrow (BM) of mice. Cell vitalities were measured by CCK8. The phenotypes and ROS of mBM-MSC were analyzed by flow cytometry. Cellular senescence was detected using SA-β-gal stains. IL-6 and CXCL1 secretions were measured by ELISA.

Results: mBM-MSC can differentiated into osteocytes and adipocytes. They expressed CD29, CD106, and Sca-1, and did not express CD31, CD45 or FLK1. Our study showed that the cell vitalities of mBM-MSC were significantly reduced after IFN-γ treatment for 5 days, and the cell numbers were obviously lower after IFN-γ treatment for 5, 10 or 15 days. The IFN-γ group increased SA-β-gal-positive cells and reactive oxygen species (ROS) significantly after 15 days of IFN-γ treatment. Moreover, IL-6 and CXCL1 secretions were upregulated by IFN-γ.

Conclusions: Our study shows IFN-γ can induce senescence-like characteristics in mBM-MSC, suggesting a novel target for anti-aging therapy.

Keywords: IFN-γ; mesenchymal stem cells; senescence.

MeSH terms

  • Adipogenesis / drug effects
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cellular Senescence / drug effects*
  • Chemokine CXCL1 / biosynthesis
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Interferon-gamma / pharmacology*
  • Interleukin-6 / biosynthesis
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Osteogenesis / drug effects
  • Reactive Oxygen Species / metabolism
  • Up-Regulation / drug effects

Substances

  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • Interleukin-6
  • Reactive Oxygen Species
  • Interferon-gamma