Alteration of PBMC transcriptome profile after interaction with multipotent mesenchymal stromal cells under “physiological” hypoxia

Abstract

Multipotent mesenchymal stromal cells (MSCs) have demonstrated a pronounced immunosuppressive activity, the manifestation of which depends on the microenvironmental factors, including O₂ 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%) O₂. As revealed with microarray analysis, PBMC transcriptome at 20% O₂ was more affected, which was manifested as differential expression of more than 300 genes, whereas under 5% O₂ 220 genes were changed. Most of genes at 20% O₂ were downregulated, while at hypoxia most of genes were upregulated. Altered gene patterns were only partly overlapped at different O₂ 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.