Priming-Dependent Modulation of Secretome in Placenta- and Adipose-Derived Mesenchymal Stromal/Stem Cells: Toward Cell-Free Immunoregenerative Therapies for Osteochondral and Degenerative Joint Diseases.

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)

Age-related joint diseases are driven by structural deterioration, chronic inflammation, and impaired regenerative capacity. Mesenchymal stromal/stem cells (MSCs) have emerged as promising therapeutic candidates due to their immunomodulatory and regenerative effects, largely mediated by their secretome and extracellular vesicles (EVs). However, the therapeutic efficacy of MSC-derived products depends on both the cell source and the conditioning stimuli to which MSCs are exposed. In this study, we characterized secretomes derived from placenta-derived MSCs (PDSCs) and adipose-derived MSCs (ASCs) by performing a comparative proteomic and exosomal microRNA (miRNA) profiling. Moreover, the impact of different priming strategies, including hypoxia, interferon-gamma (IFNγ), and interleukin-1 beta (IL1β), on the paracrine properties of these cells was assessed.Proteomic analysis identified over 7,000 proteins, with PDSC secretome enriched in pathways related to osteogenesis, chondrogenesis, extracellular matrix organization, angiogenesis, and immune regulation, whereas ASC secretome displayed limited enrichment in these processes. Functional scoring highlighted IL1β priming as the most effective strategy to enhance osteochondral and immunomodulatory protein signatures in PDSCs. Differently, IFNγ priming selectively expanded the repertoire of exosomal miRNAs, with enrichment in signall

Evidence level

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

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