Oxidative stress induces senescence in human mesenchymal stem cells

Brandl, Anita; Meyer, Matthias R.; Bechmann, Volker; Nerlich, Michael; Angele, Peter

doi:10.1016/j.yexcr.2011.02.015

Cited by 143 publications

(109 citation statements)

References 33 publications

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“…Similar to our study, Brandl et al reported that oxidative stress induces senescence in MSCs (Brandl et al 2011). More recently, we also reported that engineering of hB-MSCs with lipocalin 2 granted them many protective properties including strengthening them to withstand oxidative, hypoxia, and serum-deprivation conditions, besides the induction of antioxidants and the up-regulation of some growth factors (Halabian et al 2013).…”

Section: Discussionsupporting

confidence: 92%

“…It is strongly recommended that for MSC-based cell therapy, lower passages (passage 4 or 5) must be used. It is also known that hBMSCs finally become senescent, a feature they share with normal somatic cells (Brandl et al 2011). It should be noted that the regenerative potential of hB-MSCs is impaired by cellular senescence (Brandl et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…It is also known that hBMSCs finally become senescent, a feature they share with normal somatic cells (Brandl et al 2011). It should be noted that the regenerative potential of hB-MSCs is impaired by cellular senescence (Brandl et al 2011). Therefore, overexpression of Lcn2 in hB-MSCs not only reduces their senescence rate, but also might restore their regenerative potential.…”

Section: Discussionmentioning

confidence: 99%

“…PCR conditions for amplification of both human Lcn2 and β-actin included a The hB-MSCs were cultured in DMEM low glucose (Gibco, USA) supplemented with 10 % fetal bovine serum, 100 U/ml penicillin and 100 μg/ml streptomycin at 37°C and 5 % Co 2 in a humidified incubator. The hB-MSCs of earlier passages (between 4 and 6) were incubated with 150-μM H 2 O 2 for 2 h (Brandl et al 2011), then washed with PBS and cultivated with fresh medium.…”

Section: Plasmid Transfectionmentioning

confidence: 99%

“…Over-expression of Lcn2 down-regulates senescencerelated genes in hB-MSCs following their exposure to oxidative stress conditions Next, we studied the expression of certain genes whose expression has been attributed to senescence (Lafferty-Whyte et al 2010). To do this, the hB-MSCs were treated with 150-μM H 2 O 2 for 2 h, a condition in which cells survive but senescence is induced (as previously described by Brandl et al (2011)) followed by RNA extraction, cDNA synthesis, and real-time PCR analysis of p16, p27, and p53 gene expression. Relative expression of the genes was determined after normalization against expression of the β-actin housekeeping gene and reported as fold changes.…”

Section: Ectopic Expression Of Lcn2 In Hb-mscsmentioning

confidence: 99%

See 4 more Smart Citations

Lipocalin 2 decreases senescence of bone marrow-derived mesenchymal stem cells under sub-lethal doses of oxidative stress

Bahmani

Roudkenar

Halabian

et al. 2014

Cell Stress and Chaperones

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The regenerative potential of mesenchymal stem cells (MSCs) is impaired by cellular senescence, a multi factorial process that has various functions. However, pathways and molecules involved in senescence have not been fully identified. Lipocalin 2 (Lcn2) has been the subject of intensive research, due to its contribution to many physiological and pathophysiological conditions. The implication of Lcn2 has been reported in many conditions where senescence also occurs. In the present study, we evaluated the role of Lcn2 in the occurrence of senescence in human bone marrowderived mesenchymal stem cells (hB-MSCs) under oxidative conditions. When hB-MSCs were genetically engineered to over-express Lcn2 (MSC-Lcn2) and exposed to H 2 O 2 , the proliferation rate of the cells increased. However, the number of colonies and the number of cells that made up each colony in both MSC-V and MSC-Lcn2 cells decreased compared to those cultivated under normal conditions. Our results revealed that over-expression of recombinant Lcn2 in hB-MSCs decreases senescence induced by H 2 O 2 treatment. Senescent cells were observed in aged hB-MSCs; however, no alteration in the expression level of Lcn2 was detected compared to earlier passages. Finally, a higher amount of Lcn2 protein was detected in the plasma of the elderly than in young people.Our findings suggest that Lcn2 might restore the health and regeneration potential of MSCs by decreasing senescence.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Plasmid Transfectionmentioning

confidence: 99%

Section: Ectopic Expression Of Lcn2 In Hb-mscsmentioning

confidence: 99%

See 3 more Smart Citations

Lipocalin 2 decreases senescence of bone marrow-derived mesenchymal stem cells under sub-lethal doses of oxidative stress

Bahmani

Roudkenar

Halabian

et al. 2014

Cell Stress and Chaperones

View full text Add to dashboard Cite

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Rapid Detection of Senescent Mesenchymal Stromal Cells by a Fluorescent Probe

Ang

Lee

Raghothaman

et al. 2019

Biotechnology Journal

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Despite intense interest in human mesenchymal stromal cells (MSCs), monitoring of the progressive occurrence of senescence has been hindered by the lack of efficient detection tools. Here, the discovery of a novel MSC senescence-specific fluorescent probe (CyBC9) identified by a high-throughput screen is reported. Compared with the prototypical senescence-associated β-galactosidase (SA-β-gal) staining, the CyBC9 assay is rapid (2 h) and nontoxic and can thus be applied to live cells. It is shown that CyBC9 is able to stain early and late senescent populations both in monolayer-and in microcarrier-based cultures. Finally, to investigate the mechanism of CyBC9, colocalization assays are performed and it is found that CyBC9 is accumulated in the mitochondria of senescent MSCs presumably due to the loss of membrane potential. Taken together, it is expected that CyBC9 will be a useful tool to ameliorate cell therapy through rapid and early screening of senescent phenotypes in clinically relevant MSCs.

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Cysteine‐rich protein 61 (CCN1) mediates replicative senescence‐associated aberrant collagen homeostasis in human skin fibroblasts

Quan

Qin

Voorhees

et al. 2012

J of Cellular Biochemistry

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Dermal fibroblasts produce a collagen-rich extracellular matrix, which confers mechanical strength and resiliency to human skin. During aging, collagen production is reduced and collagen fragmentation is increased, which is initiated by matrix metalloproteinase-1 (MMP-1). This aberrant collagen homeostasis results in net collagen deficiency, which impairs the structural integrity and function of skin. Cysteine-rich protein 61 (CCN1), a member of the CCN family, negatively regulates collagen homeostasis, in primary human skin dermal fibroblasts. As replicative senescence is a form of cellular aging, we have utilized replicative senescent dermal fibroblasts to further investigate the connection between elevated CCN1 and aberrant collagen homeostasis. CCN1 mRNA and protein levels were significantly elevated in replicative senescent dermal fibroblasts. Replicative senescent dermal fibroblasts also expressed significantly reduced levels of type I procollagen and increased levels of MMP-1. Knockdown of elevated CCN1 in senescent dermal fibroblasts partially normalized both type I procollagen and MMP-1 expression. These data further support a key role of CCN1 in regulation of collagen homeostasis. Elevated expression of CCN1 substantially increased collagen lattice contraction and fragmentation caused by replicative senescent dermal fibroblasts. Atomic force microscopy (AFM) further revealed collagen fibril fragmentation and disorganization were largely prevented by knockdown of CCN1 in replicative senescent dermal fibroblasts, suggesting CCN1 mediates MMP-1-induced alterations of collagen fibrils by replicative senescent dermal fibroblasts. Given the ability of CCN1 to regulate both production and degradation of type I collagen, it is likely that elevated-CCN1 functions as an important mediator of collagen loss, which is observed in aged human skin.

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Oxidative stress induces senescence in human mesenchymal stem cells

Cited by 143 publications

References 33 publications

Lipocalin 2 decreases senescence of bone marrow-derived mesenchymal stem cells under sub-lethal doses of oxidative stress

Lipocalin 2 decreases senescence of bone marrow-derived mesenchymal stem cells under sub-lethal doses of oxidative stress

Rapid Detection of Senescent Mesenchymal Stromal Cells by a Fluorescent Probe

Cysteine‐rich protein 61 (CCN1) mediates replicative senescence‐associated aberrant collagen homeostasis in human skin fibroblasts

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