Diversity and Predicted Impact of miRNAs in Human MSCs-derived Extracellular Vesicles

Extracellular vesicles (EVs) mediate intercellular communication by transferring microRNAs (miRNAs) that regulate gene expression post-transcriptionally. EVs derived from mesenchymal stem/stromal cells (MSCs) have been widely investigated, and many studies have reported the presence of miRNAs within these vesicles. However, a comprehensive analysis comparing datasets to identify miRNA functional patterns has not yet been conducted. To address this gap, we compiled and analyzed published data on miRNAs in MSCs-derived EVs to uncover common features and explore regulatory roles. A literature search was performed to identify in vitro studies involving human MSCs that provided detailed methodologies for EVs concentration and miRNA characterization. Selected miRNA datasets were used for downstream bioinformatic analyses. Validated miRNA-target gene interactions were retrieved using MultiMiR R package. Functional enrichment analyses were performed using Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways to investigate potential biological roles of the identified genes. We curated 461 studies reporting miRNAs in MSCs-derived EVs. The most studied cells were adipose-derived (ADSCs), bone marrow-derived (BMMSCs), and umbilical cord-derived MSCs (UCMSCs), with BMMSCs contributing the highest number of unique miRNAs. hsa-miR-21-5p was the most frequently reported miRNA. For ADSCs, BMMSCs, and UCMSCs, the most frequently targeted genes were ZZZ3, ZZZ3, and PTEN, respectively. Notably, ZZZ3, a chromatin regulator, was prominent in all three cells. GO analysis revealed biological process enrichment in axonogenesis, while KEGG analysis highlighted significant involvement of neutrophil extracellular trap formation and aminoacyl-tRNA biosynthesis. This study provides an integration of miRNA data from human MSCs-derived extracellular vesicles.