Scientific article
Open access

Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells

Published inCell death and disease, vol. 4, e911
Publication date2013

Cellular senescence is the permanent arrest of cell cycle, physiologically related to aging and aging-associated diseases. Senescence is also recognized as a mechanism for limiting the regenerative potential of stem cells and to protect cells from cancer development. The senescence program is realized through autocrine/paracrine pathways based on the activation of a peculiar senescence-associated secretory phenotype (SASP). We show here that conditioned media (CM) of senescent mesenchymal stem cells (MSCs) contain a set of secreted factors that are able to induce a full senescence response in young cells. To delineate a hallmark of stem cells SASP, we have characterized the factors secreted by senescent MSC identifying insulin-like growth factor binding proteins 4 and 7 (IGFBP4 and IGFBP7) as key components needed for triggering senescence in young MSC. The pro-senescent effects of IGFBP4 and IGFBP7 are reversed by single or simultaneous immunodepletion of either proteins from senescent-CM. The blocking of IGFBP4/7 also reduces apoptosis and promotes cell growth, suggesting that they may have a pleiotropic effect on MSC biology. Furthermore, the simultaneous addition of rIGFBP4/7 increased senescence and induced apoptosis in young MSC. Collectively, these results suggest the occurrence of novel-secreted factors regulating MSC cellular senescence of potential importance for regenerative medicine and cancer therapy.

  • Apoptosis/drug effects
  • Blotting, Western
  • Cell Aging/drug effects/genetics
  • Cell Differentiation/drug effects/genetics
  • Cell Proliferation/drug effects
  • Cells, Cultured
  • Chromatography, Liquid
  • Computational Biology
  • Culture Media, Conditioned/pharmacology
  • Humans
  • Immunohistochemistry
  • Insulin-Like Growth Factor Binding Protein 4/genetics/metabolism/pharmacology
  • Insulin-Like Growth Factor Binding Proteins/genetics/metabolism/pharmacology
  • Tandem Mass Spectrometry
Citation (ISO format)
SEVERINO, Valeria et al. Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells. In: Cell death and disease, 2013, vol. 4, p. e911. doi: 10.1038/cddis.2013.445
Main files (1)
Article (Published version)
ISSN of the journal2041-4889

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