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Updated: Jun 5, 2025
Isolating, Sequencing and Analyzing Extracellular MicroRNAs from Human Mesenchymal Stem Cells
Published on: March 8, 2019
Probing the Mesenchymal Stem Cell Aging through In silico Assessment of Extracellular Vesicle-mediated miRNAs
Ningning Mi1, Xibin Liu2, Yuhua Gao3
1College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A&F University, Linan, P.R. China.
Introduction:
During mesenchymal stem cell (MSCs) aging, a decrease in its proliferation and regenerative capacity occurs, which is implicated in human aging. The MSCs aging process is regulated by genetics, metabolism, the external environment, and various complex pathways.
Method:
The aging of MSCs during in vitro culture poses a major challenge for developing cell therapy aimed at combating human diseases and aging. To identify the contributing factors underlying MSCs aging, we obtained datasets of mRNA expression changes before and after aging from the Gene Expression Omnibus (GEO) database and datasets of extracellular vesicles (EVs) microRNAs (miRNAs) expression changes (GSE153752, GSE195634, and GSE226464). We conducted an indepth analysis to screen the correlation between EVs-miRNAs and MSCs aging.
Result:
Our analysis identified significant differences in the expression of hsa-miR-146a-5p, hsamiR- 432-5p, hsa-miR-7706, hsa-miR-409-3p, and hsa-miR-17-5p in EVs before and after MSCs aging. These differences arise from the post-MSCs aging activation of signaling pathways, such as FOXO and P53, which promote the expression of hsa-miR-146a-5p, hsa-miR-432-5p, hsa-miR-7706, hsa-miR-409-3p, and hsa-miR-17-5p.
Conclusion:
Subsequently, these miRNAs are transported to EVs upon binding to the RNA-binding proteins A2BP1, SFRS2, MBNL1, EIF4B, and ACO1. This study used the correlation between MSCs aging and specific EVs-miRNAs to predict MSCs aging during the culture process.
Insights
Mesenchymal stem cell (MSC) aging, linked to human aging, involves changes in extracellular vesicle microRNAs (EV-miRNAs). Specific EV-miRNAs can predict MSC aging during culture, offering insights into cell therapy and aging processes.
Area of Science:
- Cell Biology
- Gerontology
- Biotechnology
Background:
- Mesenchymal stem cell (MSC) aging reduces proliferation and regeneration, contributing to human aging.
- MSC aging is influenced by genetic, metabolic, and environmental factors.
- In vitro MSC aging presents challenges for cell-based therapies.
Purpose of the Study:
- To identify key extracellular vesicle microRNAs (EV-miRNAs) associated with mesenchymal stem cell (MSC) aging.
- To explore the relationship between EV-miRNAs and the aging process of MSCs in vitro.
- To establish a predictive model for MSC aging using EV-miRNA profiles.
Main Methods:
- Analysis of Gene Expression Omnibus (GEO) datasets for mRNA and microRNA (miRNA) expression changes in aged MSCs.
- Screening for correlations between extracellular vesicle (EV)-miRNAs and MSC aging.
- Identification of differentially expressed EV-miRNAs (hsa-miR-146a-5p, hsa-miR-432-5p, hsa-miR-7706, hsa-miR-409-3p, hsa-miR-17-5p).
Main Results:
- Significant differences in specific EV-miRNAs were observed between young and aged MSCs.
- Signaling pathways like FOXO and P53 were activated post-aging, promoting the expression of identified EV-miRNAs.
- These miRNAs are packaged into EVs via binding to RNA-binding proteins (A2BP1, SFRS2, MBNL1, EIF4B, ACO1).
Conclusions:
- Specific EV-miRNAs serve as reliable biomarkers for predicting MSC aging in culture.
- Understanding EV-miRNA dynamics offers potential therapeutic targets for age-related diseases.
- This research provides a foundation for developing cell therapy strategies that account for MSC aging.
