Background: It is well known that mesenchymal stem cells (MSCs) are among the most promising stem cells for treatment of several inflammatory and immune diseases due to their potent immunoregulatory properties. Tideglusib is available on the market as an inhibitor of glycogen synthase kinase-3, a protein that plays an important role in the immune response. The aim of this study was to investigate the effects of tideglusib on the expression of a number of immunomodulatory genes in human bone marrow (BM)-derived MSCs. Methods: BM-MSCs were derived from patients and characterized by immunophenotyping, as well as assessment of their adipogenic and osteogenic differentiation potential. In the next step, the BM-MSCs were treated with 200 nM tideglusib for 24 h. The expression of target genes was then verified in preconditioned cells as well as the BM-MSCs without any treatment via quantitative RT-PCR. Results: The expression of immune modulatory genes, such as TDO-2, COX-2, and TSG-6 was increased (p <0.01) in BM-MSCs after tideglusib treatment. Comparing the test group with the control group, we found a decrease (p <0.01) in the expression of IL-6 as a pro-inflammatory cytokine in the test group. Conclusion: It is suggested that tideglusib plays a significant role in the upregulation of immunomodulatory genes in human BM-MSCs, and has the potential to manipulate the phenotype of MSCs to anti-inflammatory in a way that inhibits the production of pro-inflammatory cytokines such as IL-6. Hence, it may be introduced as a new class of small molecules that promote the immunomodulatory properties of MSCs and therefore can improve their clinical applications.

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