Conditioned Medium of Mesenchymal Stem Cells Pulsed with Theobromine Can Instruct Anti-Inflammatory Neutrophils

Abstract

Background: Both adenosine signaling and phosphodiesterase inhibitor agents can alter the survivability and differentiation potential of Mesenchymal Stem Cells (MSCs). On the other hand, the crosstalk between MSCs and immunocytes like neutrophils is clear. Objectives: Here, we examined the consequence of inflammatory functions of neutrophils after co-culture with conditioned MSC Medium (CM) whose MSCs had previously been pulsed with theobromine. Methods: Mesenchymal stem cells were separated and characterized by the bone marrow of Wistar rats. These cells were primed with different concentrations of theobromine (0, 10, 50, and 100 μM) for 48 hours. Neutrophils were primed with CM for four hours and their performance was examined. Results: CM primed with theobromine at low to moderate concentrations protected the neutral red removal by neutrophils and potentiated CM potential to support neutrophils from apoptosis. CM from MSC primed with theobromine augmented the phagocytosis potential of co-cultured neutrophils. Conversely, CM isolated from MSCs pulsed with theobromine reduced the production of potentially noxious reactive oxygen species and myeloperoxidase activity more profoundly than did CM from un-pulsed MSCs. Conclusions: Conditioned medium of MSCs pulsed with theobromine can instruct anti-inflammatory neutrophils.