Mesenchymal stem cell aging

Fehrer, Christine; Lepperdinger, Günter

doi:10.1016/j.exger.2005.07.006

Cited by 239 publications

(172 citation statements)

References 34 publications

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“…Second, these cells are in early senescence, as shown by the decreased telomerase activity, and it is well known that aged human MSCs show a decline in differentiation potential as well as in the proliferation rate. These data support the previously proposed concept that the inevitable reduction of telomerase activity in human committed or stressed MSCs must be challenged and that the regenerative properties of "rejuvenated" MSCs might be enhanced, with consequent therapeutic implications (36,37).…”

Section: Discussionsupporting

confidence: 87%

Impairment of endothelial cell differentiation from bone marrow–derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosis

Cipriani

Guiducci

Miniati

et al. 2007

Arthritis & Rheumatism

146

102

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Objective. Systemic sclerosis (SSc) is a disorder characterized by vascular damage and fibrosis of the skin and internal organs. Despite marked tissue hypoxia, there is no evidence of compensatory angiogenesis. The ability of mesenchymal stem cells (MSCs) to differentiate into endothelial cells was recently demonstrated. The aim of this study was to determine whether impaired differentiation of MSCs into endothelial cells in SSc might contribute to disease pathogenesis by decreasing endothelial repair.Methods. MSCs obtained from 7 SSc patients and 15 healthy controls were characterized. The number of colony-forming unit-fibroblastoid colonies was determined. After culture in endothelial-specific medium, the endothelial-like MSC (EL-MSC) phenotype was assessed according to the surface expression of vascular endothelial growth factor receptors (VEGFRs). Senescence, chemoinvasion, and capillary morphogenesis studies were also performed.Results. MSCs from SSc patients displayed the same phenotype and clonogenic activity as those from controls. In SSc MSCs, a decreased percentage of VEGFR-2؉, CXCR4؉, VEGFR-2؉/CXCR4؉ cells and early senescence was detected. After culturing, SSc EL-MSCs showed increased expression of VEGFR-1, VEGFR-2, and CXCR4, did not express CD31 or annexin V, and showed significantly decreased migration after specific stimuli. Moreover, the addition of VEGF and stromal cell-derived factor 1 to cultured SSc ELMSCs increased their angiogenic potential less than that in controls.Conclusion. Our data strongly suggest that endothelial repair may be affected in SSc. The possibility that endothelial progenitor cells could be used to increase vessel growth in chronic ischemic tissues may open up new avenues in the treatment of vascular damage caused by SSc.

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Section: Discussionsupporting

confidence: 87%

Impairment of endothelial cell differentiation from bone marrow–derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosis

Cipriani

Guiducci

Miniati

et al. 2007

Arthritis & Rheumatism

146

102

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“…For instance, human MSCs (hMSCs) were reported to cease dividing rather early (around 40 -50 population doublings), whereas murine MSCs (mMSCs), that have telomerase activity, could be passaged for more than 100 population doublings (Meirelles Lda and Nardi, 2003). Other investigators also reported for hMSCs that telomere length gradually shortened at a similar rate to non-stem cells (30 -120 bp PD À1 ) and telomerase activity was undetectable (Fehrer and Lepperdinger, 2005). However, several growth factors enhance the mitotic potential of hMSC, and we recently found that bone marrow-derived hMSCs maintained long telomeres without the upregulation of telomerase activity for more than 100 population doublings under culture with basic FGF (Yanada et al, 2006).…”

Section: Non-haematopoietic Stem Cellssupporting

confidence: 51%

Telomere and telomerase in stem cells

2007

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Telomeres, guanine-rich tandem DNA repeats of the chromosomal end, provide chromosomal stability, and cellular replication causes their loss. In somatic cells, the activity of telomerase, a reverse transcriptase that can elongate telomeric repeats, is usually diminished after birth so that the telomere length is gradually shortened with cell divisions, and triggers cellular senescence. In embryonic stem cells, telomerase is activated and maintains telomere length and cellular immortality; however, the level of telomerase activity is low or absent in the majority of stem cells regardless of their proliferative capacity. Thus, even in stem cells, except for embryonal stem cells and cancer stem cells, telomere shortening occurs during replicative ageing, possibly at a slower rate than that in normal somatic cells. Recently, the importance of telomere maintenance in human stem cells has been highlighted by studies on dyskeratosis congenital, which is a genetic disorder in the human telomerase component. The regulation of telomere length and telomerase activity is a complex and dynamic process that is tightly linked to cell cycle regulation in human stem cells. Here we review the role of telomeres and telomerase in the function and capacity of the human stem cells.

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“…Previous studies also demonstrated that decreased stemness and increased senescence are the primary causes of declines in osteogenic differentiation of BMSCs (Fehrer, & Lepperdinger, 2005; Zhou et al., 2016). In this study, we observed that the stemness and osteogenic differentiation of BMSCs were significantly reduced with increasing age, while the aging phenotype and adipogenic differentiation of aged BMSCs were markedly increased.…”

Section: Discussionmentioning

confidence: 92%

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

et al. 2018

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The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of microRNA‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT‐rich sequence‐binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci (SAHF). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.

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Mesenchymal stem cell aging

Cited by 239 publications

References 34 publications

Impairment of endothelial cell differentiation from bone marrow–derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosis

Impairment of endothelial cell differentiation from bone marrow–derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosis

Telomere and telomerase in stem cells

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

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