Bone marrow mesenchymal stem cells to ameliorate experimental autoimmune encephalomyelitis via modifying expression patterns of miRNAs.

INTRODUCTION: Clinical and experimental studies highlighted the significant therapeutic role of Mesenchymal stem cells (MSCs) in neurodegenerative diseases. MSCs possess potent immunomodulatory properties by releasing exosomes, which generate a suitable microenvironment. microRNAs (miRNAs), as one of several effective bioactive molecules of exosomes, influence cellular communication and activities in recipient cells. Recent studies revealed that miRNAs could control the progression of multiple sclerosis (MS) via differentiation and function of T helper cells (Th). METHODS: Here, we investigated the therapeutic effects of syngeneic-derived BM-MSC in experimental autoimmune encephalomyelitis (EAE) mouse model of MS by evaluating expression profile of miRNAs, pro- and anti-inflammatory in serum and brain tissues. Three-time scheme groups (6th day, 6th & 12th days, and 12th day, of post-EAE induction) were applied to determine the therapeutic effects of intraperitoneally received 1*106 of BM-MSCs. RESULTS: The expression levels of mature isoforms of miR-193, miR-146a, miR-155, miR-21, and miR-326 showed that BM-MSCs treatment attenuated the EAE clinical score and reduced clinical inflammation as well as demyelination. The improved neurological functional outcome associated with enhanced expression of miR-193 and miR-146a, but decreased expression levels of miR-155, miR-21, and miR-326 were followed by suppressing effects on Th1/Th17 immune responses (reduced levels of IFN-γand IL-17 cytokine expression) and induction of Treg cells, immunoregulatory responses (increase of IL-10, TGF-ß, and IL-4) in treatment groups. CONCLUSION: Our findings suggest that BM-MSCs administration might change expression patterns of miRNAs and downstream interactions followed by immune system modulation. However, there is a need to carry out future human clinical trials and complementary experiments.

Nanoparticle-mediated synergistic chemoimmunotherapy for tailoring cancer therapy: recent advances and perspectives.

Nowadays, a potent challenge in cancer treatment is considered the lack of efficacious strategy, which has not been able to significantly reduce mortality. Chemoimmunotherapy (CIT) as a promising approach in both for the first-line and relapsed therapy demonstrated particular benefit from two key gating strategies, including chemotherapy and immunotherapy to cancer therapy; therefore, the discernment of their participation and role of potential synergies in CIT approach is determinant. In this study, in addition to balancing the pros and cons of CIT with the challenges of each of two main strategies, the recent advances in the cancer CIT have been discussed. Additionally, immunotherapeutic strategies and the immunomodulation effect induced by chemotherapy, which boosts CIT have been brought up. Finally, harnessing and development of the nanoparticles, which mediated CIT have expatiated in detail.