Cell culture expansion media choice affects secretory, protective and immuno-modulatory features of adipose mesenchymal stromal cell-derived secretomes for orthopaedic applications.

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)

Introduction Mesenchymal stromal cells (MSCs) gained attention for their anti-inflammatory and trophic properties, with musculoskeletal diseases and osteoarthritis (OA) being among the most studied conditions. Alongside cells, their released factors and extracellular vesicles (EVs), overall termed "secretome", are actively sifted being envisioned as the main therapeutic actors. In addition to standard supplementation given by foetal bovine serum (FBS) or human platelet lysate (hPL), new good manufacturing practice (GMP)-compliant serum/xeno (S/X)-free media formulations have been proposed, although their influence on MSCs phenotype and potential is scarcely described. The aim of this study is therefore to evaluate, in the OA context, the differences in secretome composition and potential after adipose-MSCs (ASCs) cultivation in both standard (FBS and hPL) and two next generation (S/X) GMP-ready supplements. Methods Immunophenotype and secretory ability at soluble protein and EV-related levels, including embedded miRNAs, were analysed in the secretomes by means of flow cytometry, nanoparticle tracking analysis, high throughput ELISA and qRT-PCR arrays. Secretomes effect was tested in in vitro models of chondrocytes, lymphocytes and monocytes to mimic the OA microenvironment. Results Within a conserved molecular signature, a divergent fingerprint emerged for ASCs' secretomes coll

Evidence level

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

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