Resveratrol augments therapeutic efficiency of mouse bone marrow mesenchymal stem cell-based therapy in experimental autoimmune encephalomyelitis

• Published in: International journal of developmental neuroscience Vol. 49; no. 1; pp. 60 - 66
• Main Authors: Wang, Dong, Li, Shi-Ping, Fu, Jin-Sheng, Bai, Lin, Guo, Li
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.04.2016
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Cell Proliferation - drug effects; Cell Proliferation - physiology; Cell Survival; Cytokines - metabolism; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - surgery; Experimental autoimmune encephalitis; Female; Freund's Adjuvant - toxicity; L-Lactate Dehydrogenase - metabolism; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stem Cells - physiology; Mice; Mice, Inbred C57BL; Multiple sclerosis; Myelin-Oligodendrocyte Glycoprotein - toxicity; Peptide Fragments - toxicity; Resveratrol; Severity of Illness Index; Stilbenes - therapeutic use; Time Factors; Multiple sclerosis; MS; EAE; IL-4; CNS; IL-10; mBM-MSC; IFN-γ; TNF-α; Resveratrol; Experimental autoimmune encephalitis; ELISA; Mesenchymal stem cells
• ISSN: 0736-5748; 1873-474X
• DOI: 10.1016/j.ijdevneu.2016.01.005

•Both resveratrol and BM-MSCs treatment repress inflammatory responses.•Both resveratrol and BM-MSCs alleviate EAE symptoms.•Resveratrol augments therapeutic efficiency of BM-MSCs for EAE Experimental autoimmune encephalitis (EAE) is an inflammatory demyelinating disease, which served as a useful model providing considerable insights into the pathogenesis of multiple sclerosis (MS). Mouse bone marrow mesenchymal stem cells (mBM-MSC) were shown to have neuroprotection capabilities in EAE. Resveratrol is a small polyphenolic compound and possess therapeutic activity in various immune-mediated diseases. The sensitivity of mBM-MSCs to resveratrol was determined by an established cell-viability assay. Resveratrol-treated mBM-MSCs were also characterized with flow cytometry using MSC-specific surface markers and analyzed for their multiple differentiation capacities. EAE was induced in C57BL/6 mice by immunization with MOG35-55. Interferon gamma (IFN-γ)/tumor necrosis factor alpha (TNF-α) and interleukin-4 (IL-4)/interleukin-10 (IL-10), the hallmark cytokines that direct T helper type 1 (Th1) and Th2 development, were detected with enzyme-linked immunosorbent assay (ELISA). In vivo efficacy experiments showed that mBM-MSCs or resveratrol alone led to a significant reduction in clinical scores, and combined treatment resulted in even more prominent reduction. The combined treatment with mBM-MSCs and resveratrol enhanced the immunomodulatory effects, showing suppressed proinflammatory cytokines (IFN-γ, TNF-α) and increased anti-inflammatory cytokines (IL-4, IL-10). The combination of mBM-MSCs and resveratrol provides a novel potential experimental protocol for alleviating EAE symptoms.