Skip to main content
SpringerLink
Log in

Cell Senescence and Mesenchymal Stromal Cells

  • REVIEWS
  • Published:
Human Physiology Aims and scope Submit manuscript

Abstract

The aging phenomenon involves complex interrelated mechanisms at different levels of physiological processes, resulting in a decreased ability to maintain homeostasis of the organism due to organ dysfunctions. The chronic inflammation, which is progressing at the tissue level, operates as a driver of many age-related diseases. Nowadays, researchers consider cell aging (senescence) as one of the aging key hallmarks, manifested as qualitative and quantitative changes in the cellular composition and intercellular communication in tissues. This review highlights the modern concepts of aging at the cellular level. Particular attention is given to the mesenchymal stromal/stem cells (MSCs), which are involved in tissue homeostasis maintenance. Age-related MSC function alterations in tissue niches including immunomodulatory activity, hematopoiesis, and paracrine regulation are discussed. In addition, the approaches to MSC modification in vitro to attenuate the negative effects of aging are considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. McHugh, D. and Gil, J., Senescence and aging: causes, consequences, and therapeutic avenues, J. Cell Biol., 2018, vol. 217, no. 1, p. 65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhang, R., Chen, H.Z., and Liu, D.P., The four layers of aging, Cell Syst., 2015, vol. 1, no. 3, p. 180.

    Article  CAS  PubMed  Google Scholar 

  3. Moskalev, A.A., Proshkina, E.N., Belyi, A.A., and Solovyev, I.A., Genetics of aging and longevity, Russ. J. Genet.: Appl. Res., 2017, vol. 7, no. 4, p. 369.

    Article  CAS  Google Scholar 

  4. López-Otín, C., Blasco, M.A., Partridge, L., et al., The hallmarks of aging, Cell, 2013, vol. 153, no. 6, p. 1194.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Muñoz-Espín, D., Cañamero, M., Maraver, A., et al., Programmed cell senescence during mammalian embryonic development, Cell, 2013, vol. 155, no. 5, p. 1104.

    Article  PubMed  CAS  Google Scholar 

  6. Muñoz-Espín, D. and Serrano, M., Cellular senescence: from physiology to pathology, Nat. Rev. Mol. Cell Biol., 2014, vol. 15, no. 7, p. 482.

    Article  PubMed  CAS  Google Scholar 

  7. van Deursen, J.M., The role of senescent cells in ageing, Nature, 2014, vol. 509, no. 7501, p. 439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Farr, J.N., Xu, M., Weivoda, M.M., et al., Targeting cellular senescence prevents age-related bone loss in mice, Nat. Med., 2017, vol. 23, no. 9, p. 1072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gnani, D., Crippa, S., Della Volpe, L., et al., An early senescence state in aged mesenchymal stromal cells contributes to hematopoietic stem and progenitor cell clonogenic impairment through the activation of a proinflammatory program, Aging Cell, 2019, vol. 18, p. e12933.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Patil, P., Dong, Q., Wang, D., et al., Systemic clearance of p16INK4α-positive senescent cells mitigates age-associated intervertebral disc degeneration, Aging Cell, 2019, vol. 18, p. e12927.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Lewis McDougall, F.C., Ruchaya, P.J., Domenjo Vila, E., et al., Aged-senescent cells contribute to impaired heart regeneration, Aging Cell, 2019, vol. 18, p. e12931.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Hayflick, L. and Moorhead, P.S., The serial cultivation of human diploid cell strains, Exp. Cell Res., 1961, vol. 25, p. 585.

    Article  CAS  PubMed  Google Scholar 

  13. de Magalhães, J.P. and Passos, J.F., Stress, cell senescence and organismal ageing, Mech. Ageing Dev., 2018, vol. 170, p. 2.

    Article  PubMed  CAS  Google Scholar 

  14. Nakamura, A.J., Chiang, Y.J., Hathcock, K.S., et al., Both telomeric and non-telomeric DNA damage are determinants of mammalian cellular senescence, Epigenet. Chromatin, 2008, vol. 1, no. 1, p. 6.

    Article  CAS  Google Scholar 

  15. Coppé, J.P., Patil, C.K., Rodier, F., et al., Senescence-associated secretory phenotypes reveal cell non-autonomous functions of oncogenic RAS and the p53 tumor suppressor, PLoS Biol., 2008, vol. 6, p. 2853.

    Article  PubMed  CAS  Google Scholar 

  16. Pole, A., Dimri, M., and Dimri, G.P., Oxidative stress, cellular senescence and ageing, AIMS Mol. Sci., 2016, vol. 3, no. 3, p. 300.

    Article  CAS  Google Scholar 

  17. Sedelnikova, O.A., Redon, C.E., Dickey, J.S., et al., Role of oxidatively induced DNA lesions in human pathogenesis, Mutat. Res., 2010, vol. 704, p. 152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. von Zglinicki, T., Oxidative stress shortens telomeres, Trends Biochem. Sci., 2002, vol. 27, p. 339.

    Article  CAS  PubMed  Google Scholar 

  19. Campisi, J., Aging, cellular senescence, and cancer, Ann. Rev. Physiol., 2013, vol. 75, p. 685.

    Article  CAS  Google Scholar 

  20. Ragnauth, C.D., Warren, D.T., Liu, Y., et al., Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging, Circulation, 2010, vol. 121, p. 2200.

    Article  CAS  PubMed  Google Scholar 

  21. Scaffidi, P. and Misteli, T., Lamin A-dependent nuclear defects in human aging, Science, 2006, vol. 312, p. 1059.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cao, K., Blair, C.D., Faddah, D.A., et al., Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts, J. Clin. Invest., 2011, vol. 121, no. 7, p. 2833.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mitchell, S.J., Madrigal-Matute, J., Scheibye-Knudsen, M., et al., Effects of sex, strain, and energy intake on hallmarks of aging in mice, Cell Metab., 2016, vol. 23, no. 6, p. 1093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Saxton, R.A. and Sabatini, D.M., mTOR signaling in growth, metabolism, and disease, Cell, 2017, vol. 168, no. 6, p. 960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Herranz, N., Gallage, S., Mellone, M., et al., mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype, Nat. Cell Biol., 2015, vol. 17, no. 9, p. 1205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Laberge, R.-M., Sun, Y., Orjalo, A.V., et al., MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation, Nat. Cell Biol., 2015, vol. 17, no. 8, p. 1049.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. García-Prat, L., Martínez-Vicente, M., Perdiguero, E., et al., Autophagy maintains stemness by preventing senescence, Nature, 2016, vol. 529, no. 7584, p. 37.

    Article  PubMed  CAS  Google Scholar 

  28. Campisi, J. and d’Adda di Fagagna, F., Cellular senescence: when bad things happen to good cells, Nat. Rev. Mol. Cell Biol., 2007, vol. 8, no. 9, p. 729.

    Article  CAS  PubMed  Google Scholar 

  29. Salama, R., Sadaie, M., Hoare, M., and Narita, M., Cellular senescence and its effector programs, Genes Dev., 2014, vol. 28, no. 2, p. 99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Imai, Y., Takahashi, A., Hanyu, A., et al., Crosstalk between the Rb pathway and AKT signaling forms a quiescence-senescence switch, Cell Rep., 2014, vol. 7, no. 1, p. 194.

    Article  CAS  PubMed  Google Scholar 

  31. Dimri, G.P., Lee, X., Basile, G., et al., A biomarker that identifies senescent human cells in culture and in aging skin in vivo, Proc. Natl. Acad. Sci. U.S.A., 1995, vol. 92, no. 20, p. 9363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Watanabe, S., Kawamoto, S., Ohtani, N., and Hara, E., Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases, Cancer Sci., 2017, vol. 108, no. 4, p. 563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Firsanov, D.V., Solovjeva, L.V., and Svetlova, M.P., H2AX phosphorylation at the sites of DNA double-strand breaks in cultivated mammalian cells and tissues, Clin. Epigenet., 2011, vol. 2, no. 2, p. 283.

    Article  CAS  Google Scholar 

  34. Kuilman, T. and Peeper, D.S., Senescence-messaging secretome: SMS-ing cellular stress, Nat. Rev. Cancer, 2009, vol. 9, no. 2, p. 81.

    Article  CAS  PubMed  Google Scholar 

  35. Coppé, J.P., Desprez, P.Y., Krtolica, A., and Campisi, J., The senescence-associated secretory phenotype: the dark side of tumor suppression, Annu. Rev. Pathol., 2010, vol. 5, p. 99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Coppé, J.P., Kauser, K., Campisi, J., and Beauséjour, C.M., Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence, J. Biol. Chem., 2006, vol. 281, no. 40, p. 29568.

    Article  PubMed  CAS  Google Scholar 

  37. Elzi, D.J., Song, M., Hakala, K., et al., Wnt antagonist SFRP1 functions as a secreted mediator of senescence, Mol. Cell Biol., 2012, vol. 32, no. 21, p. 4388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Nelson, G., Wordsworth, J., Wang, C., et al., A senescent cell bystander effect: senescence-induced senescence, Aging Cell, 2012, vol. 11, no. 2, p. 345.

    Article  CAS  PubMed  Google Scholar 

  39. Freund, A., Orjalo, A., Desprez, P.Y., and Campisi, J., Inflammatory networks during cellular senescence: causes and consequences, Trends Mol. Med., 2010, vol. 16, p. 238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Campisi, J. and Robert, L., Cell senescence: role in aging and age-related diseases, Interdiscip. Top Gerontol., 2014, vol. 39, p. 45.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Doles, J., Storer, M., Cozzuto, L., et al., Age-associated inflammation inhibits epidermal stem cell function, Genes Dev., 2012, vol. 26, no. 19, p. 2144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Turinetto, V., Vitale, E., and Giachino, C., Senescence in human mesenchymal stem cells: functional changes and implications in stem cell-based therapy, Int. J. Mol. Sci., 2016, vol. 7, no. 7, p. E1164.

    Article  CAS  Google Scholar 

  43. Li, Y., Wu, Q., Wang, Y., et al., Senescence of mesenchymal stem cells, Int. J. Mol. Med., 2017, vol. 39, no. 4, p. 775.

    Article  CAS  PubMed  Google Scholar 

  44. Payushina, O.V., Localization and functions of mesenchymal stromal cells in vivo, Biol. Bull. Rev., 2016, vol. 6, no. 1, p. 1.

    Article  Google Scholar 

  45. Lunyak, V.V., Amaro-Ortiz, A., and Gaur, M., Mesenchymal stem cells secretory responses: senescence messaging secretome and immunomodulation perspective, Front. Genet., 2017, vol. 8, p. 220.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Ullah, I., Subbarao, R.B., and Rho, G.J., Human mesenchymal stem cells—current trends and future prospective, Biosci. Rep., 2015, vol. 35, no. 2, p. e00191.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Dominici, M., Le Blanc, K., Mueller, I., et al., Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement, Cytotherapy, 2006, vol. 8, no. 4, p. 315.

    Article  CAS  PubMed  Google Scholar 

  48. Hoogduijn, M.J., Betjes, M.G., and Baan, C.C., Mesenchymal stromal cells for organ transplantation: different sources and unique characteristics? Curr. Opin. Organ Transplant., 2014, vol. 19, no. 1, p. 41.

    Article  CAS  PubMed  Google Scholar 

  49. Mattar, P. and Bieback, K., Comparing the immunomodulatory properties of bone marrow, adipose tissue, and birth-associated tissue mesenchymal stromal cells, Front. Immunol., 2015, vol. 6, p. 560.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. McLeod, C.M. and Mauck, R.L., On the origin and impact of mesenchymal stem cell heterogeneity: new insights and emerging tools for single cell analysis, Eur. Cell Mater., 2017, vol. 34, p. 217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Andreeva, E.R. and Buravkova, L.B., Paracrine activity of multipotent mesenchymal stromal cells and its modulation in hypoxia, Hum. Physiol., 2013, vol. 39, no. 3, p. 315.

    Article  CAS  Google Scholar 

  52. Richardson, S.M., Kalamegam, G., Pushparaj, P.N., et al., Mesenchymal stem cells in regenerative medicine: focus on articular cartilage and intervertebral disc regeneration, Methods, 2016, vol. 99, p. 69.

    Article  CAS  PubMed  Google Scholar 

  53. Rubina, K.A., Kalinina, N.I., Efimenko, A.Yu., et al., Mechanism of stimulation of angiogenesis in ischemic myocardium with the help of adipose tissue stromal cells, Kardiologiya, 2010, no. 50, p. 51.

  54. Kalinina, N.I., Sysoeva, V.Yu., Rubina, K.A., et al., Mesenchymal stem cells in tissue growth and repair, Acta Nat., 2011, vol. 3, no. 4, p. 32.

    Google Scholar 

  55. Zuk, P.A., The adipose-derived stem cell: looking back and looking ahead, Mol. Biol. Cell, 2010, vol. 21, p. 1783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Natesan, S., Zhang, G., Baer, D.G., et al., A bilayer construct controls adipose-derived stem cell differentiation into endothelial cells and pericytes without growth factor stimulation, Tissue Eng., Part A, 2011, vol. 17, nos. 7–8, p. 941.

    Article  CAS  Google Scholar 

  57. Gnecchi, M., Danieli, P., Malpasso, G., and Ciuffreda, M.C., Paracrine mechanisms of mesenchymal stem cells in tissue repair, Methods Mol. Biol., 2016, vol. 1416, p. 123.

    Article  CAS  PubMed  Google Scholar 

  58. Hodgkinson, C.P., Bareja, A., Gomez, J.A., and Dzau, V.J., Emerging concepts in paracrine mechanisms in regenerative cardiovascular medicine and biology, Circ. Res., 2016, vol. 118, no. 1, p. 95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Gornostaeva, A., Andreeva, E., and Buravkova, L., Factors governing the immunosuppressive effects of multipotent mesenchymal stromal cells in vitro, Cytotechnology, 2016, vol. 68, no. 4, p. 565.

    Article  CAS  PubMed  Google Scholar 

  60. Gu, Y., Li, T., Ding, Y., et al., Changes in mesenchymal stem cells following long-term culture in vitro, Mol. Med. Rep., 2016, vol. 13, no. 6, p. 5207.

    Article  CAS  PubMed  Google Scholar 

  61. Legzdina, D., Romanauska, A., Nikulshin, S., et al., Characterization of senescence of culture-expanded human adipose-derived mesenchymal stem cells, Int. J. Stem Cells, 2016, vol. 9, no. 1, p. 124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ratushnyy, A., Lobanova, M., and Buravkova, L.B., Expansion of adipose tissue-derived stromal cells at “physiologic” hypoxia attenuates replicative senescence, Cell Biochem. Funct., 2017, vol. 35, no. 4, p. 232.

    Article  CAS  PubMed  Google Scholar 

  63. Kim, M., Kim, C., Choi, Y.S., et al., Age-related alterations in mesenchymal stem cells related to shift in differentiation from osteogenic to adipogenic potential: implication to age-associated bone diseases and defects, Mech. Ageing Dev., 2012, vol. 133, no. 5, p. 215.

    Article  PubMed  Google Scholar 

  64. Despars, G., Carbonneau, C.L., Bardeau, P., et al., Loss of the osteogenic differentiation potential during senescence is limited to bone progenitor cells and is dependent on p53, PLoS One, 2013, vol. 8, no. 8, p. e73206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wagner, W., Horn, P., Castoldi, M., et al., Replicative senescence of mesenchymal stem cells: a continuous and organized process, PLoS One, 2008, vol. 3, no. 5, p. e2213.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Digirolamo, C.M., Stokes, D., Colter, D., et al., Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate, Br. J. Haematol., 1999, vol. 107, no. 2, p. 275.

    Article  CAS  PubMed  Google Scholar 

  67. Cheng, H., Qiu, L., Ma, J., et al., Replicative senescence of human bone marrow and umbilical cord derived mesenchymal stem cells and their differentiation to adipocytes and osteoblasts, Mol. Biol. Rep., 2011, vol. 38, no. 8, p. 5161.

    Article  CAS  PubMed  Google Scholar 

  68. Stechschulte, L.A. and Lecka-Czernik, B., Reciprocal regulation of PPARγ and RUNX2 activities in marrow mesenchymal stem cells: fine balance between p38 MAPK and protein phosphatase 5, Curr. Mol. Biol. Rep., 2017, vol. 3, no. 2, p. 107.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Lee, Y.H., Lee, H.Y., Kim, T.G., et al., PPARγ maintains homeostasis through autophagy regulation in dental pulp, J. Dent. Res., 2015, vol. 94, no. 5, p. 729.

    Article  CAS  PubMed  Google Scholar 

  70. Sepúlveda, J.C., Tomé, M., Fernández, M.E., et al., Cell senescence abrogates the therapeutic potential of human mesenchymal stem cells in the lethal endotoxemia model, Stem Cells, 2014, vol. 32, no. 7, p. 1865.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Baggiolini, M. and Clark-Lewis, I., Interleukin-8, a chemotactic and inflammatory cytokine, FEBS Lett., 1992, vol. 307, p. 97.

    Article  CAS  PubMed  Google Scholar 

  72. Li, A., Dubey, S., Varney, M.L., et al., IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis, J. Immunol., 2003, vol. 170, p. 3369.

    Article  CAS  PubMed  Google Scholar 

  73. Blankenberg, S., Rupprecht, H.J., Bickel, C., et al., Circulating cell adhesion molecules and death in patients with coronary artery disease, Circulation, 2001, vol. 104, p. 1336.

    Article  CAS  PubMed  Google Scholar 

  74. Tanuma, N., Sakuma, H., Sasaki, A., and Matsumoto, Y., Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis, Acta Neuropathol., 2006, vol. 112, p. 195.

    Article  CAS  PubMed  Google Scholar 

  75. Spoettl, T., Hausmann, M., Herlyn, M., et al., Monocyte chemoattractant protein-1 (MCP-1) inhibits the intestinal-like differentiation of monocytes, Clin. Exp. Immunol., 2006, vol. 145, p. 190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Li, Y., Xu, X., Wang, L., et al., Senescent mesenchymal stem cells promote colorectal cancer cells growth via galectin-3 expression, Cell Biosci., 2015, vol. 5, p. 21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Di, G.H., Liu, Y., Lu, Y., et al., IL-6 secreted from senescent mesenchymal stem cells promotes proliferation and migration of breast cancer cells, PLoS One, 2014, vol. 9, no. 11, p. e113572.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Skolekova, S., Matuskova, M., Bohac, M., et al., Cisplatin-induced mesenchymal stromal cells-mediated mechanism contributing to decreased antitumor effect in breast cancer cells, Cell Commun. Signaling, 2016, vol. 14, p. 4.

    Article  CAS  Google Scholar 

  79. Minieri, V., Saviozzi, S., Gambarotta, G., et al., A new paradigm in cardiac regeneration: The mesenchymal stem cell secretome, Stem Cells Int., 2015, vol. 2015, p. 765846.

    Google Scholar 

  80. Özcan, S., Alessio, N., Acar, M.B., et al., Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses, Aging (N.Y.), 2016, vol. 8, no. 7, p. 1316.

    Article  Google Scholar 

  81. van Niel, G., D’Angelo, G., and Raposo, G., Shedding light on the cell biology of extracellular vesicles, Nat. Rev. Mol. Cell Biol., 2018, vol. 19, no. 4, p. 213.

    Article  CAS  PubMed  Google Scholar 

  82. Tkach, M. and Théry, C., Communication by extracellular vesicles: where we are and where we need to go, Cell, 2016, vol. 164, no. 6, p. 1226.

    Article  CAS  PubMed  Google Scholar 

  83. Liu, S., Mahairaki, V., Bai, H., et al., Highly purified human extracellular vesicles produced by stem cells alleviate aging cellular phenotypes of senescent human cells, Stem Cells, 2019, vol. 37, no. 6, p. 779.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Geiger, H., de Haan, G., and Florian, M.C., The ageing hematopoietic stem cell compartment, Nat. Rev. Immunol., 2013, vol. 13, no. 5, p. 376.

    Article  CAS  PubMed  Google Scholar 

  85. Kfoury, Y. and Scadden, D.T., Mesenchymal cell contributions to the stem cell niche, Cell Stem Cell, 2015, vol. 16, no. 3, p. 239.

    Article  CAS  PubMed  Google Scholar 

  86. Adams, G.B., Martin, R.P., Alley, I.R., et al., Therapeutic targeting of a stem cell niche, Nat. Biotechnol., 2007, vol. 25, no. 2, p. 238.

    Article  CAS  PubMed  Google Scholar 

  87. Mendez-Ferrer, S., Michurina, T.V., Ferraro, F., et al., Mesenchymal and hematopoietic stem cells form a unique bone marrow niche, Nature, 2010, vol. 466, no. 7308, p. 829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Mendelson, A. and Frenette, P.S., Hematopoietic stem cell niche maintenance during homeostasis and regeneration, Nat. Med., 2014, vol. 20, no. 8, p. 833.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Haas, S., Hansson, J., Klimmeck, D., et al., Inflammation-induced emergency megakaryopoiesis driven by hematopoietic stem cell-like megakaryocyte progenitors, Cell Stem Cell, 2015, vol. 17, no. 4, p. 422.

    Article  CAS  PubMed  Google Scholar 

  90. Pietras, E.M., Mirantes-Barbeito, C., Fong, S., et al., Chronic interleukin-1 exposure drives hematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal, Nat. Cell Biol., 2016, vol. 18, no. 6, p. 607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Bernardo, M.E. and Locatelli, F., Mesenchymal stromal cells in hematopoietic stem cell transplantation, Methods Mol. Biol., 2016, vol. 1416, p. 3.

    Article  CAS  PubMed  Google Scholar 

  92. Takeuchi, M., Takeuchi, K., Kohara, A., et al., Chromosomal instability in human mesenchymal stem cells immortalized with human papilloma virus E6, E7 and hTERT genes, In Vitro Cell Dev. Biol. Anim., 2007, vol. 43, nos. 3–4, p. 129.

    Article  CAS  PubMed  Google Scholar 

  93. Wei, F., Qu, C., Song, T., et al., Vitamin C treatment promotes mesenchymal stem cell sheet formation and tissue regeneration by elevating telomerase activity, J. Cell Physiol., 2012, vol. 227, no. 9, p. 3216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lin, T.M., Tsai, J.L., Lin, S.D., et al., Accelerated growth and prolonged lifespan of adipose tissue-derived human mesenchymal stem cells in a medium using reduced calcium and antioxidants, Stem Cells Dev., 2005, vol. 14, no. 1, p. 92.

    Article  CAS  PubMed  Google Scholar 

  95. Choi, J.R., Pingguan-Murphy, B., Wan Abas, W.A., et al., In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis, PLoS One, 2015, vol. 10, no. 1, p. e0115034.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Buravkova, L.B., Andreeva, E.R., Gogvadze, V., and Zhivotovsky, B., Mesenchymal stem cells and hypoxia: where are we? Mitochondrion, 2014, vol. 19, part A, p. 105.

  97. Gharibi, B., Farzadi, S., Ghuman, M., and Hughes, F.J., Inhibition of Akt/mTOR attenuates age-related changes in mesenchymal stem cells, Stem Cells, 2014, vol. 32, no. 8, p. 2256.

    Article  CAS  PubMed  Google Scholar 

  98. Okada, M., Kim, H.W., Matsuura, K., et al., Abrogation of age-induced microRNA-195 rejuvenates the senescent mesenchymal stem cells by reactivating telomerase, Stem Cells, 2016, vol. 34, no. 1, p. 148.

    Article  CAS  PubMed  Google Scholar 

  99. Gharibi, B. and Hughes, F.J., Effects of medium supplements on proliferation, differentiation potential and in vitro expansion of mesenchymal stem cells, Stem Cells Transl. Med., 2012, vol. 1, no. 11, p. 771.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The study was supported by the Russian Foundation for Basic Research (project no. 19-015-00150) and the scholarship of the President of the Russian Federation (no. SP-960.2019.4).

Author information

Authors and Affiliations

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

    A. Yu. Ratushnyy & L. B. Buravkova

Authors
  1. A. Yu. Ratushnyy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. B. Buravkova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to A. Yu. Ratushnyy or L. B. Buravkova.

Ethics declarations

The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

Additional information

Translated by M. Batrukova

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ratushnyy, A.Y., Buravkova, L.B. Cell Senescence and Mesenchymal Stromal Cells. Hum Physiol 46, 85–93 (2020). https://doi.org/10.1134/S0362119720010132

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0362119720010132

Keywords:

Search

Navigation