Microvesicles as Potential Biomarkers for the Identification of Senescence in Human Mesenchymal Stem Cells.

摘要: Senescence in human mesenchymal stem cells (MSCs) not only contributes to organism aging and the development of a variety diseases but also severely impairs their therapeutic properties as promising cell therapy. Studies searching for efficient biomarkers that represent cellular senescence have attracted much attention; however, no single marker currently provides an accurate cell-free representation senescence. Here, we studied characteristics MSC-derived microvesicles (MSC-MVs) may reflect parental MSCs. We found senescent late passage (LP) MSCs secreted higher levels MSC-MVs with smaller size than did early (EP) MSCs, level CD105+ decreased Also, substantially weaker ability promote osteogenesis was observed LP EP MSC-MVs. Comparative analysis RNA sequencing showed same trend decreasing number highly-expressed miRNAs increasing passages both Most genes corresponding were involved regulation senescence-related diseases, such Alzheimer's disease. Furthermore, based on miRNA profiling, transcription factors (TF) regulatory networks MSC senescence, datasets from GEO database, confirmed expression miR-146a-5p resembled state Our findings provide evidence are key factor senescence-associated secretory phenotype demonstrate integrated can dynamically representing potential biomarker monitoring