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.

Interferon-Gamma Impairs Maintenance and Alters Hematopoietic Support of Bone Marrow Mesenchymal Stromal Cells

“…A recent study by Yang et al claimed that IFN-γ induces senescence-like characteristics in murine MSC, which could explain our findings that MSC maintenance is impaired upon exposure to IFN-γ [ 43 ]. In contrast, Chinnadurai et al, showed that prelicensing with IFN-γ can correct some of the senescence-associated characteristics of cultured human MSC [ 44 ].…”

Chronic Inflammation-Induced Senescence Impairs Immunomodulatory Properties of Synovial Fluid Mesenchymal Stem Cells in Rheumatoid Arthritis

“…Cellular senescence is activated during intrinsic stress such as extensive cell replication and/or extrinsic stress like ultraviolet radiation, oxidative damage, activated oncogenes, and chronic in ammation. In particular, during chronic in ammation that occurs with liver cirrhosis, hematopoietic stem cell-associated disorders, chronic human immunode ciency virus (HIV) infection, myelodysplastic syndromes, ulcerative colitis and LRA, immune cells produce strong oxidizing genotoxic substances that are able to induce the cellular senescence [18][19][20][21]. In the in ammation milieu, pro-in ammatory cytokines are produced from stimulated lymphocytes by antigens or pathogens and activate immune cells, inhibit proliferation of transformed cells and intensify anti-viral/-tumor effects on cells; moreover, they also induce cellular senescence in diverse kinds of cells including melanocytes, endothelial cells and MSCs [10,[21][22][23][24][25].…”

“…In particular, during chronic in ammation that occurs with liver cirrhosis, hematopoietic stem cell-associated disorders, chronic human immunode ciency virus (HIV) infection, myelodysplastic syndromes, ulcerative colitis and LRA, immune cells produce strong oxidizing genotoxic substances that are able to induce the cellular senescence [18][19][20][21]. In the in ammation milieu, pro-in ammatory cytokines are produced from stimulated lymphocytes by antigens or pathogens and activate immune cells, inhibit proliferation of transformed cells and intensify anti-viral/-tumor effects on cells; moreover, they also induce cellular senescence in diverse kinds of cells including melanocytes, endothelial cells and MSCs [10,[21][22][23][24][25]. Because cellular senescence is de ned as the irreversible changes that inhibit cellular division, growth, and function, senescent MSCs from an experimentally-induced model as well as RA and systemic lupus erythematosus (SLE) patients exhibit degradation of distinct cellular features, including differentiation potential, immunomodulation properties, misregulation of proin ammatory cytokine production and reduction in migratory ability [2,5,10,11,19,21,[23][24][25][26][27][28].…”

Th1 Biased Progressive Autoimmunity in Aged Aire-Deficient Mice Accelerated Thymic Epithelial Cell Senescence

“…It was found that IFN-γ could induce senescence-like characteristics in mouse bone marrow mesenchymal stem cells [40]. The accumulation of IFN-γ-producing effector CD4 + T cells in the mediastinal lymph nodes contribute to myocardial aging [41]. Together, these data suggest that the progressively increased peripheral Th1 cells in the patients with autoimmune diseases facilitate their reentry into the thymus and contribute to accelerated thymic involution.…”