血管生长素
祖细胞
医学
少突胶质细胞
细胞生物学
内皮祖细胞
免疫学
血管生成
生物
干细胞
癌症研究
内科学
髓鞘
中枢神经系统
作者
Takakuni Maki,Anna Morancho,Pablo Martínez San Segundo,Kazuhide Hayakawa,Hajime Takase,Anna C. Liang,Marina Gabriel-Salazar,Esperanza Medina-Gutiérrez,Kazuo Washida,Joan Montaner,Josephine Lok,Eng H. Lo,Ken Arai,Anna Rosell
出处
期刊:Stroke
[Ovid Technologies (Wolters Kluwer)]
日期:2018-04-01
卷期号:49 (4): 1003-1010
被引量:71
标识
DOI:10.1161/strokeaha.117.019346
摘要
Endothelial progenitor cells (EPCs) have been extensively investigated as a therapeutic approach for repairing the vascular system in cerebrovascular diseases. Beyond vascular regeneration per se, EPCs may also release factors that affect the entire neurovascular unit. Here, we aim to study the effects of the EPC secretome on oligovascular remodeling in a mouse model of white matter injury after prolonged cerebral hypoperfusion.The secretome of mouse EPCs was analyzed with a proteome array. In vitro, the effects of the EPC secretome and its factor angiogenin were assessed on primary oligodendrocyte precursor cells and mature human cerebral microvascular endothelial cells (hCMED/D3). In vivo, mice were subjected to permanent bilateral common carotid artery stenosis, then treated with EPC secretome at 24 hours and at 1 week, and cognitive outcome was evaluated with the Y maze test together with oligodendrocyte precursor cell proliferation/differentiation and vascular density in white matter at 4 weeks.Multiple growth factors, cytokines, and proteases were identified in the EPC secretome, including angiogenin. In vitro, the EPC secretome significantly enhanced endothelial and oligodendrocyte precursor cell proliferation and potentiated oligodendrocyte precursor cell maturation. Angiogenin was proved to be a key factor since pharmacological blockade of angiogenin signaling negated the positive effects of the EPC secretome. In vivo, treatment with the EPC secretome increased vascular density, myelin, and mature oligodendrocytes in white matter and rescued cognitive function in the mouse hypoperfusion model.Factors secreted by EPCs may ameliorate white matter damage in the brain by boosting oligovascular remodeling.
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