title: Human marrow stromal cells reduce microglial activation to protect motor neurons in a transgenic mouse model of amyotrophic lateral sclerosis.
abstract: BACKGROUND
  Human marrow stromal cells (hMSCs) injected intrathecally can effectively increase the lifespan and protect motor neurons in a transgenic mouse model of amyotrophic lateral sclerosis. However, how the transplanted cells exert a neuroprotective effect is still unclear. More recently, the anti-inflammation effect of marrow stromal cells has generated a great deal of interest. In the present study, we sought to investigate whether intrathecally injected hMSCs protect motor neurons through attenuating microglial activation and the secretion of inflammatory factors in Cu/Zn superoxide dismutase 1 (SOD1) transgenic mice. In addition, we also focused on the mode of hMSCs inhibiting microglial activation.
  
  
  METHODS
  We transplanted hMSCs into the cisterna magna of SOD1 mice at the age of 8, 10 and 12 weeks. At sacrifice, tissues were harvested for analysis of neuron counts, microglial activation, TNFα secretion and inducible nitric oxide synthase (iNOS) protein expression. In vitro, microglial cells were treated with hMSC co-culture, hMSC transwell culture or hMSC conditioned medium to investigate the mode of hMSCs exerting an anti-inflammation effect.
  
  
  RESULTS
  Intrathecally transplanted hMSCs inhibited inflammatory response in SOD1 transgenic mice, which was evidenced by the decreases in microglial activation, TNFα secretion and iNOS protein expression. In addition, the inhibitory effect on microglial activation of hMSCs was through secretion of diffusible molecules adjusted to environmental cues.
  
  
  CONCLUSIONS
  Intrathecally injected hMSCs can attenuate microglial activation through secretion of diffusible molecules to exert a therapeutic effect in SOD1 transgenic mice. Further studies are needed to explore the exact mechanisms by which hMSCs inhibit inflammation for facilitating the therapeutic effect.
authors: Department of Neurology, The Affiliated Hospital of Medical College, Qingdao University, 16 Jiangsu Road, Qingdao, Shandong 266003, PR China.
authors: Chang
authors: C
authors: Zhou
authors: Chen
authors: C
authors: Zhang
authors: Renliang
authors: R
authors: Zhao
authors: Song
authors: S
authors: Chi
authors: Ping
authors: P
authors: Ge
authors: Cheng
authors: C
authors: Zhang
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000628:therapy*; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002452:Cell Count; D064987:Cell- and Tissue-Based Therapy; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D013116:Spinal Cord / Q000473:pathology; D017154:Stromal Cells / Q000502:physiology* / Q000637:transplantation; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C000606290:SOD1 protein, human; D014409:Tumor Necrosis Factor-alpha; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
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