title: Resveratrol augments therapeutic efficiency of mouse bone marrow mesenchymal stem cell-based therapy in experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000 HeBei, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000 HeBei, PR China.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000 HeBei, PR China.
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: Fu
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000 HeBei, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000 HeBei, PR China. Electronic address: ligguoer@sina.com.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000601:surgery*; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D000077185:Resveratrol; D012720:Severity of Illness Index; D013267:Stilbenes / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D013267:Stilbenes; C445081:myelin oligodendrocyte glycoprotein (35-55); D005620:Freund's Adjuvant; D007770:L-Lactate Dehydrogenase; D000077185:Resveratrol
keywords: Experimental autoimmune encephalitis; Mesenchymal stem cells; Multiple sclerosis; Resveratrol