Senescence of mesenchymal stem cells: implications in extracellular vesicles, miRNAs and their functional and therapeutic potentials

He, Liangge; Li, Mingzhu; Liu, Zhen; Padhiar, Arshad Ahmed

doi:10.31491/apt.2023.03.107

APT

2023

DOI: 10.31491/apt.2023.03.107

|View full text |Cite

Senescence of mesenchymal stem cells: implications in extracellular vesicles, miRNAs and their functional and therapeutic potentials

Liangge He

Mingzhu Li

Zhen Liu

et al.

Abstract: Senescence is seen as the cellular counterpart of tissue and biological aging, with irreversible stagnation of cell growth, and changes in function and behavior. Mesenchymal stem cells (MSCs) are one of the key therapeutic tools in regenerative medicine, and their regenerative and therapeutic potential declines significantly with the increasing age of cell donors and prolonged continuous culture in vitro. MicroRNAs (miRNAs) are regarded as important players in regulating the expression and function of multiple… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article2

Relationship

Self Cite0

Independent2

Authors

Journals

Cited by 2 publications

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Effects of Replicative Senescence of Human Chorionic MSCs on their EV-miRNA Profile

Košuthová,

Fecskeová,

Matejová

et al. 2024

Stem Cell Rev and Rep

View full text Add to dashboard Cite

Chorionic mesenchymal stromal cells (CHO-MSCs) and their extracellular vesicles (EVs) are becoming increasingly popular, since chorion is ethically harmless and an easily accessible source of MSCs. However, until now there is only a limited number of studies with a thorough characterization of CHO-MSCs derived EVs and their miRNA profile. In this study, we monitored changes in the EV-miRNA profile between early and late passage of human CHO-MSCs. First, senescence of CHO-MSCs was induced by serial passaging and confirmed by morphological changes, shortened telomeres and changes in the expression of selected genes. The expression of MSCs-specific surface markers CD73, CD90, CD105 did not change with increasing passages. Next, EVs and their miRNA profiles were compared between early vs late passage cells. Number of EVs and their size were not significantly changed. Seven of the top 10 most expressed EV-miRNAs were common to both early and late passages. A differential expression study between early and late passages identified 37 significantly differentially expressed EV-miRNAs, out of which 23 were found to be associated with pathways of cellular senescence based on KEGG pathway analysis. A set of 9 miRNAs were identified as the most frequently associated with senescence and/or with the most altered expression between early and late passages, out of which miR-145-5p, miR-335-5p and miR-199b-3p were the most significant downregulated miRNAs in late passages. The most upregulated EV-miRNAs were miR-1307-3p, miR-3615 and miR320b. Targeting these miRNAs in future experiments may prolong the therapeutic potential of CHO-MSCs and their EVs. Graphical Abstract

show abstract

Effects of Replicative Senescence of Human Chorionic MSCs on their EV-miRNA Profile

Košuthová,

Fecskeová,

Matejová

et al. 2024

Stem Cell Rev and Rep

View full text Add to dashboard Cite

show abstract

Nek6 regulates autophagy through the mTOR signaling pathway to alleviate cerebral ischemia–reperfusion injury

Wang,

Liu,

Yuan

et al. 2024

Mol Brain

View full text Add to dashboard Cite

Objective Cerebral ischemia–reperfusion injury (CIRI) is a major obstacle to neurological recovery after clinical treatment of ischemic stroke. The aim of this study was to investigate the molecular mechanism of Nek6 alleviating CIRI through autophagy after cerebral ischemia. Materials and methods A mouse model of CIRI was constructed by middle cerebral artery occlusion (MCAO). TUNEL staining was used to observe the apoptosis of neuronal cells. The oxygen glucose deprivation/reoxygenation (OGD/R) model was established by hypoxia and reoxygenation. The cell apoptosis and activity was detected. Western blot was performed to detect the expression of autophagy-related proteins, protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and adenosine 5’-monophosphate-activated protein kinase (AMPK)/mTOR signaling pathway-related proteins. Cellular autophagy flux was observed by fluorometric method. NIMA-related kinase 6 (Nek6) mRNA stability was detected by actinomycin D treatment. Methylation RNA immunoprecipitation technique was used to detect Nek6 methylation level. Results Nek6 expression was increased in both MCAO and OGD/R models. Overexpression of Nek6 in OGD/R inhibited apoptosis, decreased LC3II and Beclin-1 expression, increased p62 expression, and occurred lysosome dysfunction. Interference with Nek6 has opposite results. Nek6 overexpression promoted p-Akt and p-mTOR protein expressions, inhibited p-AMPK and p-UNC-51-like kinase 1 protein expressions and cell apoptosis, while LY294002, Rapamycin or RSVA405 treatment reversed this effect. Abnormal methyltransferase·like protein 3 (METTL3) expression in CIRI enhanced m6A modification and promoted Nek6 expression level. Conclusion This study confirmed that Nek6 regulates autophagy and alleviates CIRI through the mTOR signaling pathway, which provides a novel therapeutic strategy for patients with ischemic stroke in the future.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Senescence of mesenchymal stem cells: implications in extracellular vesicles, miRNAs and their functional and therapeutic potentials

Cited by 2 publications

References 128 publications

Effects of Replicative Senescence of Human Chorionic MSCs on their EV-miRNA Profile

Effects of Replicative Senescence of Human Chorionic MSCs on their EV-miRNA Profile

Nek6 regulates autophagy through the mTOR signaling pathway to alleviate cerebral ischemia–reperfusion injury

Contact Info

Product

Resources

About