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

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.