Evaluation of immunomodulatory effects of co-culture or supernatant of dexamethasone or IFN-γ-treated adipose-derived mesenchymal stem cells on spleen mononuclear cells

Although mesenchymal stem cells (MSCs) have exhibited promising immunomodulatory potential in preclinical studies, clinical studies have revealed variable results. These results often depend on environmental cues. Pre-conditioning MSCs with cytokines is one of the methods used to enhance their immunomodulatory effects. In this study, we harvested adipose-derived MSCs from mice and cultured them with different doses of the cytokine, IFN-γ, and the corticosteroid drug, dexamethasone, in order to investigate their effects on MSC immunosuppressive function. We found the co-culture or supernatant of MSCs, pre-conditioned with IFN-γ, together with spleen mononuclear cells resulted in a significant reduction of mononuclear cell proliferation. Although the supernatant of MSCs, pre-conditioned with dexamethasone, showed similar results, dexamethasone pre-conditioning of co-cultured MSCs increased mononuclear cell proliferation. The results further our understanding of immune-related effects of MSCs which may provide a basis for further in vivo studies to achieve better clinical results. We propose that pre-conditioning with cytokines might be an effective method to boost the immunomodulatory effects of MSCs.

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities.

Regulatory T cells (Tregs) are an immunosuppressive subgroup of CD4+ T cells which are identified by the expression of forkhead box protein P3 (Foxp3). The modulation capacity of these immune cells holds an important role in both transplantation and the development of autoimmune diseases. These cells are the main mediators of self-tolerance and are essential for avoiding excessive immune reactions. Tregs play a key role in the induction of peripheral tolerance that can prevent autoimmunity, by protecting self-reactive lymphocytes from the immune reaction. In contrast to autoimmune responses, tumor cells exploit Tregs in order to prevent immune cell recognition and anti-tumor immune response during the carcinogenesis process. Recently, numerous studies have focused on unraveling the biological functions and principles of Tregs and their primary suppressive mechanisms. Due to the promising and outstanding results, Tregs have been widely investigated as an alternative tool in preventing graft rejection and treating autoimmune diseases. On the other hand, targeting Tregs for the purpose of improving cancer immunotherapy is being intensively evaluated as a desirable and effective method. The purpose of this review is to point out the characteristic function and therapeutic potential of Tregs in regulatory immune mechanisms in transplantation tolerance, autoimmune diseases, cancer therapy, and also to discuss that how the manipulation of these mechanisms may increase the therapeutic options.

Religion, Spirituality and Risk of Coronary Heart Disease: A Matched Case-Control Study and Meta-Analysis.

Although the association between religion/spirituality (R/S) and psychological outcomes is well established, current understanding of the association with cardiovascular disease remains limited. We sought to investigate the association between Islamic R/S and coronary heart disease (CHD), and place these findings in light of a meta-analysis. In this case-control study, 190 cases with non-fatal CHD were identified and individually matched with 383 hospital-based controls. R/S was measured by self-administered 102 items questionnaire. A tabular meta-analysis was performed of observational studies on R/S (high level versus low level) and CHD. In addition, a dose-response meta-analysis was conducted using generalized least-squares regression. Participants in the top quartile had decreased odds of CHD comparing to participants in the lowest quartile of religious belief (OR 0.20, 95% confidence interval (CI) 0.06-0.59), religious commitment (OR 0.36, CI 95% 0.13-0.99), religious emotions (OR 0.39, CI 95% 0.18-0.87), and total R/S score (OR 0.30, CI 95% 0.13-0.67). The meta-analysis study showed a significant relative risk of 0.88 (CI 95% 0.77-1.00) comparing individuals in high level versus low level of R/S. In dose-response meta-analysis, comparing people with no religious services attendance, the relative risks of CHD were 0.77 (CI 95% 0.65-0.91) for one times attendance and 0.27 (CI 95% 0.11-0.65) for five times attendance per month. R/S was associated with a significantly decreased risk of CHD. The possible causal nature of the observed associations warrants randomized clinical trial with large sample size.