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Endothelial progenitor cell-conditioned medium promotes angiogenesis and is neuroprotective after spinal cord injury

摘要Endothelial progenitor cells secrete a variety of growth factors that inhibit inflammation,promote angiogenesis and exert neuroprotective effects.Therefore,in this study,we investigated whether endothelial progenitor cell-conditioned medium might have therapeutic effectiveness for the treatment of spinal cord injury using both in vitro and in vivo experiments.After primary culture of bone marrow-derived macrophages,lipopolysaccharide stimulation was used to classically activate macrophages to their proinflammatory phenotype.These cells were then treated with endothelial progenitor cell-conditioned medium or control medium.Polymerase chain reaction was used to determine mRNA expression levels of related inflammatory factors.Afterwards,primary cultures of rat spinal cord neuronal cells were prepared and treated with H2O2 and either endothelial progenitor cell-conditioned medium or control medium.Hoechst 33258 and propidium iodide staining were used to calculate the proportion of neurons undergoing apoptosis.Aortic ring assay was performed to assess the effect of endothelial progenitor cell-conditioned medium on angiogenesis.Compared with control medium,endothelial progenitor cell-conditioned medium mitigated the macrophage inflammatory response at the spinal cord injury site,suppressed apoptosis,and promoted angiogenesis.Next,we used a rat model of spinal cord injury to examine the effects of the endothelial progenitor cell-conditioned medium in vivo.The rats were randomly administered intraperitoneal injection of PBS,control medium or endothelial progenitor cell-conditioned medium,once a day,for 6 consecutive weeks.Immunohistochemistry was used to observe neuronal morphology.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was performed to detect the proportion of apoptotic neurons in the gray matter.The Basso,Beattie and Bresnahan Locomotor Rating Scale was used to evaluate the recovery of motor function of the bilateral hind limbs after spinal cord injury.Compared with the other two groups,the number of axons was increased,cavities in the spinal cord were decreased,the proportion of apoptotic neurons in the gray matter was reduced,and the Basso,Beattie and Bresnahan score was higher in the endothelial progenitor cell-conditioned medium group.Taken together,the in vivo and in vitro results suggest that endothelial progenitor cell-conditioned medium suppresses inflammation,promotes angiogenesis,provides neuroprotection,and promotes functional recovery after spinal cord injury.

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作者单位 Department of Orthopedics, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China;Department of Spine Surgery, Hefei Binhu Hospital, the Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China [1] Department of Orthopedics, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China [2]
DOI 10.4103/1673-5374.232484
发布时间 2018-07-18(万方平台首次上网日期,不代表论文的发表时间)
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中国神经再生研究(英文版)

中国神经再生研究(英文版)

2018年13卷5期

887-895页

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