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标题:Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Modify Microglial Response and Improve Clinical Outcomes in Experimental Spinal Cord Injury.
时间:2020-02-14 18:49:12
DOI:10.1038/s41598-017-18867-w
PMID:29323194
作者:Katherine A. Ruppert;Tin T. Nguyen;Karthik S. Prabhakara
出版源: 《Scientific Reports》 ,2018 ,8 (1)
摘要:Despite intensive research and clinical trials with numerous therapeutic treatments, traumatic brain injury (TBI) is a serious public health problem in the United States. There is no effective FDA-approved treatment to reduce morbidity and mortality associated with TBI. Inflammation plays a pivotal role in the pathogenesis of TBI. We looked to re-purpose existing drugs that reduce immune... [Show full abstract]
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目录:
  • Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Modify Microglial Response and Improve Clinical Outcomes in E ...
    • Materials and Methods
      • Isolation and culture of human mesenchymal stromal cells (hMSCs).
      • Isolation of EVs by sequential filtration.
      • Characterization of EVs.
        • Particle size distribution and quantification by Nanoparticle tracking analysis (NTA).
      • Flow cytometry analysis of rat tissue.
      • Animals.
      • Spinal Cord Contusion and EV treatment.
      • Behavioral Testing.
      • Hind limb Motor Function.
      • Mechanical Sensitivity.
      • Immunohistochemistry.
      • Exclusion Criteria.
      • Statistical Analysis.
      • Data Availability.
    • Results
      • MSCEv Attenuate Microglia Activation Pathways.
      • MSCEv treatment following SCI results in improved locomotor recovery.
      • Mechanical Sensitivity Threshold Improved with MSCEv.
      • Treatment with MSCEv+ from Inflammation-Stimulated MSC Improves Sensory Function.
      • MSCEv Effects on Immune Response in Blood and Spleen.
      • MSCEv Decreases Reactive Microglia and Astrocytes.
    • Discussion
    • Figure 1 Microglia activation in injured spinal cord Samples of spinal cord tissue containing the injury epicenter (a) were analyzed by flow cytometry for microglia activation state phenotypes.
    • Figure 2 Animals treated with MSCEVs displayed significantly higher locomotor recovery scores when compared to sham and untreated SCI animals.
    • Figure 3 Animals treated with MSCEvs exhibited significantly higher force threshold (*p < 0.
    • Figure 4 Animals treated with MSCEv+ exhibited significantly higher force threshold (**p < 0.
    • Figure 5 Flow cytometry of spleen tissue and blood samples from each animal provide evidence of anti-inflammatory effects of MSCEvwt/MSCEv+ treatment.
    • Figure 6 Longitudinal and coronal sections of spinal cord at 14 days post-injury were stained for Iba-1 (microglia, green), GFAP (astrocytes, red), and DAPI (nuclei, blue) and analyzed for neuroinflammation.

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