Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
Journal Citation Indicator (JCI) (2023) – 0.4
Scopus CiteScore – 3.7 (CiteScore Tracker – 4.0)
Index Copernicus  – 171.00; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 2, March-April, p. 201–206

doi: 10.17219/acem/61431

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

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

Zhou Xin Yang1,A,B,C,D,F, Gen Xiang Mao1,A,B,C,F, Jing Zhang1,B,E,F, Xiao Lin Wen1,B,C, Bing Bing Jia1,B,C, Yi Zhong Bao1,B, Xiao Ling Lv1,C, Ya Zhen Wang1,B, Guo Fu Wang1,A,C,E,F

1 Zhejiang Provincial Key Lab of Geriatrics, Zhejiang Hospital, Hangzhou, China

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

Key words

IFN-γ, senescence, mesenchymal stem cells

References (26)

  1. Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9:641–650.
  2. Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418:41–49.
  3. Wang Y, Zhang Z, Chi Y, et al. Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation. Cell Death Dis. 2013;4:e950.
  4. Wagner W, Horn P, Castoldi M, et al. Replicative senescence of mesenchymal stem cells: A continuous and organized process. PLoS One. 2008;3:e2213.
  5. Choo KB, Tai L, Hymavathee KS, et al. Oxidative stress-induced premature senescence in Wharton’s jelly-derived mesenchymal stem cells. Int J Med Sci. 2014;11:1201–1207.
  6. Estrada JC, Torres Y, Benguria A, et al. Human mesenchymal stem cell-replicative senescence and oxidative stress are closely linked to aneu-ploidy. Cell Death Dis. 2013;4:e691.
  7. Bonab MM, Alimoghaddam K, Talebian F, Ghaffari SH, Ghavamzadeh A, Nikbin B. Aging of mesenchymal stem cell in vitro. BMC Cell Biol. 2006;7:14.
  8. Kasper G, Mao L, Geissler S, et al. Insights into mesenchymal stem cell aging: Involvement of antioxidant defense and actin cytoskeleton. Stem Cells. 2009;27:1288–1297.
  9. Nauta AJ, Fibbe WE: Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007;110:3499–3506.
  10. Krampera M, Cosmi L, Angeli R, et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells. 2006;24:386–398.
  11. Croitoru-Lamoury J, Lamoury FM, Caristo M, et al. Interferon-gamma regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (ido). PLoS One. 2011;6:e14698.
  12. Ren G, Zhao X, Zhang L, et al. Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression. J Immunol. 2010;184:2321–2328.
  13. Ren G, Zhang L, Zhao X, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008;2:141–150.
  14. Braumuller H, Wieder T, Brenner E, et al. T-helper-1-cell cytokines drive cancer into senescence. Nature. 2013;494:361–365.
  15. Wang S, Zhou M, Lin F, et al. Interferon-gamma induces senescence in normal human melanocytes. PLoS One. 2014;9:e93232.
  16. Kim KS, Kang KW, Seu YB, Baek SH, Kim JR. Interferon-gamma induces cellular senescence through p53-dependent DNA damage signaling in human endothelial cells. Mech Ageing Dev. 2009;130:179–188.
  17. Chen K, Wang D, Du WT, et al. Human umbilical cord mesenchymal stem cells huc-mscs exert immunosuppressive activities through a pge2-dependent mechanism. Clin Immunol. 2010;135:448–458.
  18. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105:1815–1822.
  19. Watanabe Y, Suzuki O, Haruyama T, Akaike T. Interferon-gamma induces reactive oxygen species and endoplasmic reticulum stress at the hepatic apoptosis. J Cell Biochem. 2003;89:244–253.
  20. Weyemi U, Lagente-Chevallier O, Boufraqech M, et al. Ros-generating nadph oxidase nox4 is a critical mediator in oncogenic h-ras-induced DNA damage and subsequent senescence. Oncogene. 2012;31:1117–1129.
  21. Coppe JP, Patil CK, Rodier F, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic ras and the p53 tumor suppressor. PLoS Biol. 2008;6:2853–2868.
  22. Chien Y, Scuoppo C, Wang X, et al. Control of the senescence-associated secretory phenotype by nf-kappab promotes senescence and en-hances chemosensitivity. Genes Dev. 2011;25:2125–2136.
  23. Coppe JP, Patil CK, Rodier F, et al. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS One. 2010;5:e9188.
  24. Chomarat P, Banchereau J, Davoust J, Palucka AK. IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat Immunol. 2000;1:510–514.
  25. Ritzman AM, Hughes-Hanks JM, Blaho VA, Wax LE, Mitchell WJ, Brown CR. The chemokine receptor cxcr2 ligand kc (cxcl1) mediates neutro-phil recruitment and is critical for development of experimental lyme arthritis and carditis. Infect Immun. 2010;78:4593–4600.
  26. Dhawan P, Richmond A. Role of cxcl1 in tumorigenesis of melanoma. J Leukoc Biol. 2002;72:9–18.
© Wroclaw Medical University