title: Mechanism of mesenchymal stem cell-induced neuron recovery and anti-inflammation.
abstract: OBJECTIVE
  After ischemic or hemorrhagic stroke, neurons in the penumbra surrounding regions of irreversible injury are vulnerable to delayed but progressive damage as a result of ischemia and hemin-induced neurotoxicity. There is no effective treatment to rescue such dying neurons. Mesenchymal stem cells (MSCs) hold promise for rescue of these damaged neurons. In this study, we evaluated the efficacy and mechanism of MSC-induced neuro-regeneration and immune modulation.
  
  
  METHODS
  Oxygen-glucose deprivation (OGD) was used in our study. M17 neuronal cells were subjected to OGD stress then followed by co-culture with MSCs. Rescue effects were evaluated using proliferation and apoptosis assays. Cytokine assay and quantitative polymerase chain reaction were used to explore the underlying mechanism. Antibody and small molecule blocking experiments were also performed to further understand the mechanism.
  
  
  RESULTS
  We showed that M17 proliferation was significantly decreased and the rate of apoptosis increased after exposure to OGD. These effects could be alleviated via co-culture with MSCs. Tumor necrosis factor-α was found elevated after OGD stress and was back to normal levels after co-culture with MSCs. We believe these effects involve interleukin-6 and vascular endothelial growth factor signaling pathways.
  
  
  CONCLUSIONS
  Our studies have shown that MSCs have anti-inflammatory properties and the capacity to rescue injured neurons.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Nichole
authors.initials: N
authors.lastname: Gebhart
authors.affiliation: Department of Pharmacology and Psychiatry, Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Elliott
authors.initials: E
authors.lastname: Richelson
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Brott
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Meschia
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA. Electronic address: Zubair.Abba@Mayo.edu.
authors.forename: Abba C
authors.initials: AC
authors.lastname: Zubair
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002450:Cell Communication; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D009443:Neuritis / Q000378:metabolism / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D020521:Stroke / Q000473:pathology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D005947:Glucose
keywords: MSC; immune modulation; neuro-regeneration; stroke