Effect of Short-Term Hypoxic Stress on Immunosuppressive Activity of Perivascular Multipotent Stromal Cells

Abstract

Multipotent mesenchymal stromal cells (MSCs) are stromal precursors with the capacity to differentiate in osteo-, adipo-, and chondrodirections and participate in repair, regeneration, and immune response. Those abilities, especially immunosuppression, make MSCs a perspective tool for cell therapy and regenerative medicine. Short-term hypoxic stress can occur in damaged tissues and negatively affect MSC capacities to modulate functions of activated peripheral blood mononuclear cells (PBMCs). In the present paper, we evaluated the impact of short-term hypoxic stress (<1% oxygen) on immunosuppressive potential of tissue oxygen (5%) adapted MSCs. At a tissue oxygen level, we detected an increase of the ratio of innate immune cells (natural killers, NK) and a decrease in the ratio of adaptive immune cells (HLA-DR⁺ Т-cells) within floating PBMCs in the presence of MSCs. Additionally, inhibition of T-cell proliferation was observed. Within adhered PBMCs, the ratio of monocytes was higher and the ratio of NK T cells was lower. Short-term hypoxic stress did not affect MSC immunosuppression toward lymphocytes in suspension. Nevertheless, a decrease in percent of monocytes and NK T cells within adhered PBMCs was detected. Thus, hypoxic stress did not influence immunosuppressive activity of MSCs toward floating PBMCs. Attenuation of monocyte adhesion to MSCs upon cell-to-cell interaction may negatively impact the formation of MSCeducated macrophage phenotype with anti-inflammatory activity. In vivo, it may provoke the slowdown of “response to injury” during inflammation.