The investigation of the relationship between anti-inflammatory lipid mediators and immunomodulatory effects of mesenchymal stem cells

Mesenchymal stem cells (MSCs) are adult stem cells that initially isolated from bone marrow and after the large number of follow-up studies they also could isolated from a variety of sources, including fat tissue, dental tissues, fetal tissues. These cells can differentiate into the mesenchymal cells such as cartilage, bone and fat cells. However, due to their unique immunomodulation ability, they are used in the clinic, especially lethal acute graft versus host disease (GVHD) and different autoimmune diseases. In this study, we aimed to investigate the effects of anti-inflammatory lipid mediators Lipoxin A4 and Resolvin D1 molecules, on the immunomodulation ability of MSCs. For this purpose, we co-cultured activated peripheral blood mononuclear cells (PBMC) with adipose tissue-derived MSCs at different effector: target ratios. In order to better understand the efficacy of Lipoxin A4 and Resolvin D1 we were repeated the same experiments by conducting a plasmid transfection encoding the 15-lipoxygenase (15-LOX) gene in MSCs. In order to compare the activities, we were determined the levels of Lipoxin A4, Resolvin D1, IFN-g, IL-4, IL-10 and IL-17a from cell culture supernatants by ELISA. According to our findings, we observed that Lipoxin A4 increased the immunomodulation ability of MSCs especially at high E:T ratios. We observed that the immunomodulation effects of 15-LOX transfected cells were significantly higher than the naive MSCs. In conclusion, we have found that Lipoxin A4 and Resolvin D1 molecules may not have a direct effect on the immunomodulation ability of naive MSCs, but that MSCs expressing 15-LOX enzyme, which plays a direct role in the synthesis of these molecules, may show a superior effect compared with normal cells. In order to reach more accurate results, we need to support our data with in-vivo models.