| Description |
The senescence in human mesenchymal stem cells (MSCs) contributes to organism aging and the development of a variety of diseases, and severely impairs therapeutic properties of MSCs as a promising cell therapy. The studies searching for efficient biomarkers that practically represent cellular senescence have attracted many attentions; however, no single marker currently provides an accurate and practically cell-free representation of cellular senescence. Here, we studied characteristics of MSC-derived microvesicles (MSC-MVs) regarding their capacities of resembling the senescence in their parental MSCs. We found that senescent late passage (LP) MSCs secreted higher levels of MSC-MVs with smaller size than did early passage (EP) MSCs, and the level of CD105+ MSC-MVs decreased with the senescence in the parental MSCs. In addition, substantially weaker ability to promote the osteogenesis in MSCs was found in LP than EP MSC-MVs. Next, our comparative analysis of RNA sequencing showed the same trend of decreasing number of highly-expressed miRNAs with passages in both MSCs and MSC-MVs, and that most of the highly-expressed genes in LP MSCs and MSC-MVs are both involved in the regulation of senescence-related diseases, such as Alzheimer's disease. Furthermore, based on the obtained miRNA, transcription factor (TF) and genes regulatory network of MSC senescence and the dataset from GEO databases, we confirmed the expression of miR-146a-5p in MSC-MVs resembled the senescent state of their parental MSCs. Our findings give support to MSC-MVs as a key factor in the senescence-associated secretory phenotype of MSCs and demonstrate that their integrated characteristics can dynamically resemble the MSC senescence state, representing a potential biomarker in precise identifying and real-time monitoring of MSC senescence in vitro and even in vivo. |
