Alteration of PBMC transcriptome profile after interaction with multipotent mesenchymal stromal cells under "physiological" hypoxia.

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

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• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Multipotent mesenchymal stromal cells (MSCs) have demonstrated a pronounced immunosuppressive activity, the manifestation of which depends on the microenvironmental factors, including O 2 level. Here we examined the effects of MSCs on transcriptomic profile of allogeneic phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) after interaction at ambient (20%) or "physiological" hypoxia (5%) O 2 . As revealed with microarray analysis, PBMC transcriptome at 20% O 2 was more affected, which was manifested as differential expression of more than 300 genes, whereas under 5% O 2 220 genes were changed. Most of genes at 20% O 2 were downregulated, while at hypoxia most of genes were upregulated. Altered gene patterns were only partly overlapped at different O 2 levels. A set of altered genes at hypoxia only was of particular interest. According to Gene Ontology a part of above genes was responsible for adhesion, cell communication, and immune response. At both oxygen concentrations, MSCs demonstrated effective immunosuppression manifested as attenuation of T cell activation and proliferation as well as anti-inflammatory shift of cytokine profile. Thus, MSC-mediated immunosuppression is executed with greater efficacy at a "physiological" hypoxia, since the same result has been achieved through a change in the expression of a fewer genes in target PBMCs.

Evidence level

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

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