Mesenchymal stromal cells conditioned by peripheral blood mononuclear cells exert enhanced immunomodulation capacities and alleviate a model of Myasthenia Gravis.

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 Mesenchymal Stromal Cells (MSC) possess innate immunomodulatory properties, which can be significantly enhanced through co-culture with peripheral blood mononuclear cells (PBMC), making them attractive tools for the treatment of autoimmune and inflammatory diseases. Methods Leveraging a multi-omics approach encompassing RNA sequencing, flow and mass cytometry, secretome analysis, completed by functional evaluations, we investigated the mechanisms underpinning PBMC conditioning of MSC in vitro and their benefits in an animal model of Myasthenia gravis. MSC derived from human adipose tissue were left untreated in resting state (rMSC), conditioned by PBMC (cMSC), or activated by the pro-inflammatory molecule interferon (IFN)-γ (γMSC), then compared for their gene expression profiles, phenotypes and functional capacities. Results RNA sequencing identified 244 differentially expressed genes in cMSC compared to rMSC, highlighting key immune mediators such as CCL2, CCL11, DPP4, ICAM1, IL6, PDCD1LG2, TNFRSF11B, TNIP1, TNIP3 and ZC3H12A and pinpointing genes involved in matrix remodeling, paracrine and autocrine communications. Comparatively, 2089 genes were differentially expressed between rMSC and γMSC, highlighting host defense, anti-viral response, NFκB signaling pathways modulated by IFN-γ. Flow and mass cytometry analyses revealed upregulation of the surface markers CD2

Evidence level

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

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