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

Int J Dev Neurosci. 2016 Apr:49:60-6. doi: 10.1016/j.ijdevneu.2016.01.005. Epub 2016 Jan 28.

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.

Keywords: Experimental autoimmune encephalitis; Mesenchymal stem cells; Multiple sclerosis; Resveratrol.

MeSH terms

  • 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*
  • Female
  • Freund's Adjuvant / toxicity
  • L-Lactate Dehydrogenase / metabolism
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein / toxicity
  • Peptide Fragments / toxicity
  • Resveratrol
  • Severity of Illness Index
  • Stilbenes / therapeutic use*
  • Time Factors

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Stilbenes
  • myelin oligodendrocyte glycoprotein (35-55)
  • Freund's Adjuvant
  • L-Lactate Dehydrogenase
  • Resveratrol