Characterization of Extracellular Vesicles from Infrapatellar Fat Pad Mesenchymal Stem/Stromal Cells Expanded Using Regulatory-Compliant Media and Inflammatory/Hormonal Priming.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Osteoarthritis (OA) remains a leading cause of disability worldwide, with no disease-modifying therapies currently available for treatment. The infrapatellar fat pad (IFP) harbors mesenchymal stem/stromal cells (MSC) with potent immunomodulatory and regenerative properties, making them a promising candidate for OA treatment. A growing body of evidence suggests that the therapeutic effects of MSC are largely mediated by their extracellular vesicles (EVs), which carry bioactive cargo that modulates inflammation and tissue repair. However, optimizing MSC-derived EVs as a cell-free therapeutic approach requires an in-depth understanding of how culture conditions and inflammatory/hormonal priming influence their functional properties. In this study, IFP-MSC were expanded in regulatory-compliant human platelet lysate (HPL) and xeno-/serum-free (XFSF) media and primed with an inflammatory/fibrotic cocktail (TIC) with oxytocin (OXT) to assess the impact on their immunophenotypic profile and EV cargo. The immunophenotype confirmed that TIC+OXT-primed MSC retained key immunomodulatory surface markers, while EV characterization verified the successful isolation of CD63+/CD9+ vesicles. Pathway enrichment analysis of both HPL- and XFSF- TIC+OXT EVs cargo identified key miRNAs associated with immune regulation, tissue repair, and anabolic signaling. Functional assays revealed that TIC+OXT EV

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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