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Modification of the Properties of Extracellular Matrix of Senescent Mesenchymal Stem Cells

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Cell senescence leads to changes in the secretory activity of mesenchymal stem cells (MSC), including proteins of extracellular matrix (ECM). Here we studied the regulatory properties of ECM of senescent MSC in a model with endothelial cells (EC). EC were seeded onto a decellularized extracellular matrix of senescent MSC. Changes in cell morphology and a decrease in cell growth were observed. In addition, increased production of inflammatory chemokines MCP-1 and GROα and reduced synthesis of proangiogenic growth factor FGF-2 were revealed. Analysis of ECM showed quantitative and qualitative changes, including fibronectin layer morphology, total protein content, and concentration of deposited growth factors such as VEGF. Thus, our work demonstrates that senescence of MSC can lead to modification of the effects of their ECM on EC activity.

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References

  1. Pittenger MF, Discher DE, Péault BM, Phinney DG, Hare JM, Caplan AI. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen. Med. 2019;4:22. https://doi.org/10.1038/s41536-019-0083-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kehl D, Generali M, Mallone A, Heller M, Uldry AC, Cheng P, Gantenbein B, Hoerstrup SP, Weber B. Proteomic analysis of human mesenchymal stromal cell secretomes: a systematic comparison of the angiogenic potential. NPJ Regen. Med. 2019;4:8. https://doi.org/10.1038/s41536-019-0070-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Turinetto V, Vitale E, Giachino C. Senescence in human mesenchymal stem cells: functional changes and implications in stem cell-based therapy. Int. J. Mol. Sci. 2016;17(7):1164. https://doi.org/10.3390/ijms17071164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lunyak VV, Amaro-Ortiz A, Gaur M. Mesenchymal stem cells secretory responses: senescence messaging secretome and immunomodulation perspective. Front. Genet. 2017;8:220. https://doi.org/10.3389/fgene.2017.00220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ratushnyy A, Ezdakova M, Buravkova L. Secretome of senescent adipose-derived mesenchymal stem cells negatively regulates angiogenesis. Int. J. Mol. Sci. 2020;21(5):1802. https://doi.org/10.3390/ijms21051802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ratushnyy AY, Buravkova LB. Cell senescence and mesenchymal stromal cells. Hum. Physiol. 2020;46(1):85-93. https://doi.org/10.1134/S0362119720010132

    Article  Google Scholar 

  7. Ghosh D, Mejia Pena C, Quach N, Xuan B, Lee AH, Dawson MR. Senescent mesenchymal stem cells remodel extracellular matrix driving breast cancer cells to a more-invasive phenotype. J. Cell Sci. 2020;133(2):jcs232470. https://doi.org/10.1242/jcs.232470

  8. Bertolo A, Baur M, Guerrero J, Pötzel T, Stoyanov J. Autofluorescence is a reliable in vitro marker of cellular senescence in human mesenchymal stromal cells. Sci. Rep. 2019;9(1):2074. https://doi.org/10.1038/s41598-019-38546-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of cellular senescence. Trends Cell Biol. 2018;28(6):436-453. https://doi.org/10.1016/j.tcb.2018.02.001

    Article  CAS  PubMed  Google Scholar 

  10. Frescas D, Roux CM, Aygun-Sunar S, Gleiberman AS, Krasnov P, Kurnasov OV, Strom E, Virtuoso LP, Wrobel M, Osterman AL, Antoch MP, Mett V, Chernova OB, Gudkov AV. Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody. Proc. Natl Acad. Sci. USA. 2017;114(9):E1668-E1677. https://doi.org/10.1073/pnas.1614661114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005;120(4):513-522. https://doi.org/10.1016/j.cell.2005.02.003

    Article  CAS  PubMed  Google Scholar 

  12. Mavrogonatou E, Pratsinis H, Papadopoulou A, Karamanos NK, Kletsas D. Extracellular matrix alterations in senescent cells and their significance in tissue homeostasis. Matrix Biol. 2019;75-76:27-42. https://doi.org/10.1016/j.matbio.2017.10.004

    Article  CAS  PubMed  Google Scholar 

  13. Selman M, Pardo A. From pulmonary fibrosis to progressive pulmonary fibrosis: a lethal pathobiological jump. Am. J. Physiol. Lung Cell. Mol. Physiol. 2021;321(3):L600-L607. https://doi.org/10.1152/ajplung.00310.2021

  14. Bauer AL, Jackson TL, Jiang Y. Topography of extracellular matrix mediates vascular morphogenesis and migration speeds in angiogenesis. PLoS Comput. Biol. 2009;5(7):e1000445. https://doi.org/10.1371/journal.pcbi.1000445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shibuya M. Vascular Endothelial Growth Factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer. 2011;2(12):1097-1105. https://doi.org/10.1177/1947601911423031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Claesson-Welsh L, Welsh M. VEGFA and tumour angiogenesis. J. Intern. Med. 2013;273(2):114-127. https://doi.org/10.1111/joim.12019

    Article  CAS  PubMed  Google Scholar 

  17. Liu L, Ratner BD, Sage EH, Jiang S. Endothelial cell migration on surface-density gradients of fibronectin, VEGF, or both proteins. Langmuir. 2007;23(22):11 168-11 173. https://doi.org/10.1021/la701435x

  18. Claffey KP, Abrams K, Shih SC, Brown LF, Mullen A, Keough M. Fibroblast growth factor 2 activation of stromal cell vascular endothelial growth factor expression and angiogenesis. Lab. Invest. 2001;81(1):61-75. https://doi.org/10.1038/labinvest.3780212

    Article  CAS  PubMed  Google Scholar 

  19. Ponticos M. Connective tissue growth factor (CCN2) in blood vessels. Vascul. Pharmacol. 2013;58(3):189-193. https://doi.org/10.1016/j.vph.2013.01.004

    Article  CAS  PubMed  Google Scholar 

  20. Ungvari Z, Valcarcel-Ares MN, Tarantini S, Yabluchanskiy A, Fülöp GA, Kiss T, Csiszar A. Connective tissue growth factor (CTGF) in age-related vascular pathologies. Geroscience. 2017;39(5-6):491-498. https://doi.org/10.1007/s11357-017-9995-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia

    D. K. Matveeva, M. I. Ezdakova & A. Yu. Ratushnyy

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  1. D. K. Matveeva
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  2. M. I. Ezdakova
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  3. A. Yu. Ratushnyy
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Correspondence to A. Yu. Ratushnyy.

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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 119-125, June, 2023

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Matveeva, D.K., Ezdakova, M.I. & Ratushnyy, A.Y. Modification of the Properties of Extracellular Matrix of Senescent Mesenchymal Stem Cells. Bull Exp Biol Med 175, 569–575 (2023). https://doi.org/10.1007/s10517-023-05905-z

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  • DOI: https://doi.org/10.1007/s10517-023-05905-z

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