Extracellular vesicles from primed Hoffa's fat pad mesenchymal stem/stromal cells in osteoarthritis therapy: effects on cells critical to osteoarthritis progression.

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)

Background Since Hoffa's fat pad (HFP) is naturally involved in the joint environment, and given findings that HFP-derived mesenchymal stromal cells (MSCs) possess better chondrogenic differentiation capacity than other adipose tissue sources or bone marrow, we aimed to analyze HFP-MSCs derived extracellular vesicles (EVs) primed with blood products as potential cell-free osteoarthritis (OA) therapy. Methods HFP-MSCs were cultured under 3D conditions on microcarriers in vertical-wheel bioreactors. Prior to medium harvest, MSCs were primed with blood products, including fetal calf serum (FCS), platelet-rich plasma (PRP), or hyperacute serum (HypACT). EVs were isolated via ultrafiltration and characterized via cryo-electron microscopy, nanoparticle tracking analysis (NTA) in both scatter and fluorescence modes, as well as via Western blot (WB). CFSE-labeled EV internalization by chondrocytes and synovial fibroblasts was detected using fluorescent confocal microscopy in the presence or absence of polybrene. Polybrene was used to enhance EV internalization and potentially improve treatment efficacy in cells. To simulate an OA environment, chondrocytes and synovial fibroblasts were co-cultured with M1 macrophages. Gene expression changes were analyzed via RT-qPCR, while cytokine release was quantified using ELISA. Results HFP-MSC-EVs downregulated the expression of catabolic enzyme

Evidence level

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

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