Comparative analysis of adipose-, bone marrow-, and amniotic membrane-derived MSC secretomes and EVs reveals shared and source-specific therapeutic signatures for osteoarthritis.

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)

Aim: Mesenchymal stromal cells (MSCs) exert their therapeutic effects in osteoarthritis (OA) primarily through paracrine signaling, including secreted proteins and extracellular vesicle (EV)-associated microRNAs (miRNAs). However, the contribution of tissue origin to the composition and function of these secretomes remains unclear. This study aimed to provide a comprehensive molecular and functional comparison of secretomes from adipose-derived (ASCs), bone marrow-derived MSCs (BMSCs) and human amniotic membrane-derived MSCs, with a specific focus on OA-relevant pathways. Methods: MSCs were immunophenotyped by flow cytometry. Secretomes were profiled for 200 factors and 784 EV-miRNAs. Functional enrichment was performed using Gene Ontology and Reactome databases. In vitro , secretomes were tested on interleukin (IL)-1β-stimulated human chondrocytes to assess modulation of OA-related gene expression. Results: All MSC secretomes shared a core of factors enriched in anti-inflammatory and matrix-regulatory functions. ASCs showed the differential expression of a few modulators, potentially shifting their chondroprotective phenotype. EV-miRNAs further distinguished the MSC types. ASCs and BMSCs clustered closely in both overall miRNA content and functional enrichment, which included pathways for extracellular matrix organization, angiogenesis and IL-6 signaling. BMSC- and ASC-EVs had

Evidence level

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

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