The Importance of Stem Cell Senescence in Regenerative Medicine

Khademi-Shirvan, Maliheh; Ghorbaninejad, Mahsa; Hosseini, Samaneh; Eslaminejad, Mohamadreza Baghaban

doi:10.1007/5584_2020_489

Cited by 12 publications

(11 citation statements)

References 104 publications

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“…Emerging evidence has demonstrated that multiple factors, including cell species, tissue source, isolation method, culture conditions, and cellular status, may explain the inconsistency in the features and characteristics of MSCs in some preclinical and clinical trials. A recent study showed that aging is an important factor affecting MSC properties and functions[ 17 ]. Age-dependent decline in MSC number and function was found in old individuals[ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Senescent mesenchymal stem/stromal cells and restoring their cellular functions

Meng¹,

Liu²,

Lu³

et al. 2020

WJSC

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Mesenchymal stem/stromal cells (MSCs) have various properties that make them promising candidates for stem cell-based therapies in clinical settings. These include self-renewal, multilineage differentiation, and immunoregulation. However, recent studies have confirmed that aging is a vital factor that limits their function and therapeutic properties as standardized clinical products. Understanding the features of senescence and exploration of cell rejuvenation methods are necessary to develop effective strategies that can overcome the shortage and instability of MSCs. This review will summarize the current knowledge on characteristics and functional changes of aged MSCs. Additionally, it will highlight cell rejuvenation strategies such as molecular regulation, non-coding RNA modifications, and microenvironment controls that may enhance the therapeutic potential of MSCs in clinical settings.

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Section: Introductionmentioning

confidence: 99%

Senescent mesenchymal stem/stromal cells and restoring their cellular functions

Meng¹,

Liu²,

Lu³

et al. 2020

WJSC

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“…Mesenchymal stem cells (MSCs) are used to accelerate wound healing and several methods allow their expansion using large-scale cell culture [Satija et al, 2009]. The success of MSCs therapy depends on a prolonged ex vivo culture, which eventually undergoes an aging process [Shojaei et al, 2019;Khademi-Shirvan et al, 2020]. Traditionally, MSCs are cultured in a two-dimensional (2D) system of standard tissue culture flask; however, in monolayer culture the microenvironment is quite different from that in vivo.…”

Section: Introductionmentioning

confidence: 99%

Design and characterization of microspheres for a 3D mesenchymal stem cell culture

Lastra

Ribelles

Cortizo

2020

Colloids and Surfaces B: Biointerfaces

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“…In order to better simulate the process of physiological aging, we extracted MSCs from young (1 to 2 months) and old (15 to 18 months) rats, respectively, as the research object to explore the molecular mechanisms underlying aging. There are distinct morphological and molecular biological differences in young and senescent cells, such as increased cell surface area, decreased aspect ratio, and irregular cell bodies, accompanied by cellular metabolic disorders, decreased autophagy, and cell cycle arrest [ 23 – 25 ]. Consistent herewith, MSCs from old rats exhibited senescence-like characteristics in morphology, including irregular shapes, enlarged and flattened cell bodies.…”

Section: Discussionmentioning

confidence: 99%

RNA sequencing profiles reveal dynamic signaling and glucose metabolic features during bone marrow mesenchymal stem cell senescence

Sun

Gao

et al. 2022

Cell Biosci

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Background Stem cell senescence is considered as a significant driver of organismal aging. As individuals age, the number of stem cells is declined, and the ability to proliferate and survive is also weakened. It has been reported that metabolism plays an important role in stem cell self-renewal, multilineage differentiation, senescence and fate determination, which has aroused widespread concerns. However, whether metabolism-related genes or signalling pathways are involved in physiological aging remain largely undetermined. Results In the current study, we showed 868 up-regulated and 2006 down-regulated differentially expressed genes (DEGs) in bone marrow mesenchymal stem cells (MSCs) from old rats in comparison with that from young rats by performing RNA sequence. And DEGs functions and pathways were further selected by function enrichment analysis. The results indicated that the high expression of DEGs might participate in cell differentiation, growth factor binding and etc., while the down-regulated DEGs were majorly enriched in metabolism process, such as the cellular metabolic process and mitochondria. Then, we screened and verified DEGs related to glucose metabolism and investigated the glycolysis levels. We identified that glucose uptake, lactate secretion, ATP production and relative extracellular acidification rates (ECAR) were all diminished in MSCs from old rats. More importantly, we conducted microRNA prediction on the key DEGs of glycolysis to elucidate the potential molecular mechanisms of glucose metabolism affecting MSC senescence. Conclusions Our study unravelled the profiles of DEGs in age-associated MSC senescence and their functions and pathways. We also clarified DEGs related to glucose metabolism and down-regulated glycolysis level in age-associated MSC senescence. This study will uncover the metabolic effects on regulating stem cell senescence, and provide novel therapeutic targets for ameliorating age-associated phenotypes.

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The Importance of Stem Cell Senescence in Regenerative Medicine

Cited by 12 publications

References 104 publications

Senescent mesenchymal stem/stromal cells and restoring their cellular functions

Senescent mesenchymal stem/stromal cells and restoring their cellular functions

Design and characterization of microspheres for a 3D mesenchymal stem cell culture

RNA sequencing profiles reveal dynamic signaling and glucose metabolic features during bone marrow mesenchymal stem cell senescence

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