Effect of Constant Inflammation on In Vitro Expanded Adipose-derived Mesenchymal Stromal Cells.

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)

Human adipose-derived mesenchymal stromal cells (AD-MSCs) are known for their immunomodulatory responses to inflammation, a key trait for their therapeutic use in tissue injury and chronic inflammatory diseases. However, the effects of constant inflammation on their transcriptomic profile, proliferative capacity, and immunosuppressive potential remain largely unexplored. To investigate this, we evaluated the in vitro response of human AD-MSCs from three donors expanded across seven passages under, non-inflamed (DMEM), acute (IFNγ-24 h) and constant (IFNγ-C) inflammatory conditions. Bulk RNA-sequencing results demonstrated that AD-MSCs respond significantly to inflammatory stimuli. Both acute and constant inflammation induced extensive transcriptomic alterations, with differentially expressed genes related to cell cycle regulation, DNA replication, metabolism, and immunomodulation. Notably, constant inflammation was associated with a transcriptomic shift toward oxidative phosphorylation (OXPHOS). Moreover, microscopy analysis revealed a significant reduction in AD-MSCs proliferative capacity under constant inflammation, as evidenced by lower cumulative population doubling and the appearance of senescence-like morphological changes in early passages when compared to non-inflamed (DMEM) and acute inflammatory (IFNγ-24 h) conditions. Despite proliferation being impaired, co-culture

Evidence level

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

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