Mesenchymal Stem Cells: The Potential Therapeutic Cell Therapy to Reduce Brain Stroke Side Effects

J Stroke Cerebrovasc Dis. 2021 May;30(5):105668. doi: 10.1016/j.jstrokecerebrovasdis.2021.105668. Epub 2021 Feb 23.


Tissue plasminogen activator (tPA) is the gold standard treatment for ischemic stroke in the time window of 3-4.5 hours after the onset of symptoms. However, tPA administration is associated with inflammation and neurotoxic effects. Mesenchymal stem cells (MSC)-based therapy is emerging as a promising therapeutic strategy to control different inflammatory conditions. This project was designed to examine the protective role of MSC administration alone or in combination with royal jelly (RJ) five hours after stroke onset. The mice model of middle cerebral artery occlusion (MCAO) was established and put to six groups, including intact (healthy mice without stroke), control (untreated stroke), treated with mouse MSC (mMSC), Sup (conditioned medium), RJ and combination of mMSC and RJ (mMSC/RJ). Thereafter, behavioral functions, serum and brain (in both infarcted and non-infarcted tissues) levels of interleukin (IL)-1β, IL-4, IL-10, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) the sizes of brain infarction have been determined in the groups. Administration of mMSC and mMSC/RJ significantly improved the behavioral functions when compared to the controls. mMSC, RJ and mMSC/RJ significantly decreased the infarcted volumes. RJ and mMSC/RJ, but not mMSC, significantly decreased the brain edema. The infarction increased the serum levels of the cytokines, except TNF-α, and treatment with mMSC, Sup and RJ reduced serum levels of the pro-inflammatory cytokines. mMSC reduced IL-1β in the non-infarcted brain tissue. To conclude, data revealed that using mMSC/RJ combination significantly reduced stroke side effects, including brain edema and serum levels of pro-inflammatory cytokines, and suggested that combination therapy of MSCs with RJ may be considered as an effective stroke therapeutic strategy.

Keywords: Cytokine, Apoptosis; MSCs; Royal Jelly; Stroke.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Behavior, Animal / drug effects
  • Biomarkers / blood
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Brain Edema / blood
  • Brain Edema / pathology
  • Brain Edema / physiopathology
  • Brain Edema / prevention & control*
  • Cells, Cultured
  • Combined Modality Therapy
  • Cytokines / blood
  • Disease Models, Animal
  • Fatty Acids / pharmacology*
  • Infarction, Middle Cerebral Artery / blood
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology
  • Infarction, Middle Cerebral Artery / therapy*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mice, Inbred BALB C
  • Neuroprotective Agents / pharmacology*


  • Anti-Inflammatory Agents
  • Biomarkers
  • Cytokines
  • Fatty Acids
  • Neuroprotective Agents
  • royal jelly