A Comprehensive Bioinformatics Analysis of the Proteomic Landscape and Therapeutic Potential of EDIL3-Enriched Extracellular Vesicles Derived from Y201 Mesenchymal Stromal Cells

Abstract

Mesenchymal stromal cells (MSCs) are recognised for their regenerative capabilities, but their clinical application is often limited by cellular heterogeneity. Recent research highlights the therapeutic potential of extracellular vesicles (EVs) as key mediators of MSC function, facilitating intercellular communication and modulating various biological processes. This research investigates the proteomic landscape of EVs derived from Y201 MSCs, focusing on EDIL3, a prominent protein implicated in the pathogenesis of osteoarthritis. To achieve this, we employed a comprehensive bioinformatics pipeline that included pathway enrichment analysis, network construction, Matrisome protein classification, and functional enrichment. Our findings revealed significant enrichment in focal adhesion (FA) pathways, emphasising the critical roles of integrins and their interactions with proteins such as EDIL3. A core protein module consisting of EDIL3, MFGE8, and ITGB5 was identified, with functional annotation confirming the enrichment of the coagulation factor 5/8 C-terminal domain within this core module. Additionally, the potential role of Y201 EVs in OA pathogenesis was explored, particularly through EDIL3's involvement in pathways related to collagen-containing extracellular matrix and coagulation processes. This research enhances our understanding of EV heterogeneity and the specific contributions of individual proteins in mediating the therapeutic effects of Y201 MSCs. In conclusion, by linking the properties of Y201 MSC EVs, particularly the presence of EDIL3, integrins, and collagen proteins, we established a more comprehensive theoretical framework for further investigation into the therapeutic potential of Y201 MSC EVs by targeting specific pathways involved in OA progression.