Conditioned medium-preconditioned EPCs enhanced the ability in oligovascular repair in cerebral ischemia neonatal rats.
Conditioned medium-preconditioned EPCs enhanced the ability in oligovascular repair in cerebral ischemia neonatal rats.
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条件培养基预处理的EPCs增强脑缺血新生大鼠少血管修复能力
DOI：
10.1186/s13287-021-02157-4
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发表时间：
2021-02-12
影响因子：
7.5
通讯作者：
Yao R
中科院分区：
文献类型：
--
作者：
Zhou N;Wang L;Fu P;Cui Z;Ge Y;Jiang F;Liu J;Ren C;Luan Z;Fan H;Yao R
背景少突胶质前体细胞（OPCs）与脑内皮细胞之间的相互作用是由少突胶质生态位介导的。opc -内皮营养偶联的破坏可能会加剧脑白质损伤（WMI）的进展，因为内皮细胞在病变情况下不能提供足够的支持。据报道，内皮祖细胞（EPCs）通过促进少血管重塑来改善成人脑WMI。缺氧内皮细胞预处理EPCs （EC-pEPCs）的条件培养基在WMI中的作用是必要的，因为EPCs通常在血脑屏障破坏时被招募并发挥重要作用。在此，我们研究了EC-pEPCs对新生大鼠WMI模型中少血管重构的影响。方法采用TUNEL和流式细胞仪（FACS）分析体外条件培养基诱导氧-葡萄糖剥夺损伤的脑微血管内皮细胞（OGD-EC-CM） OPC凋亡。western blot和FACS检测EPCs对EC损伤的影响及细胞因子C-X-C基序配体12 （CXCL12）的表达。通过western blot和沉默RNA验证了EC-pEPCs的CM对OPC细胞凋亡的抑制作用。在体内，P3大鼠幼崽在P7时接受右颈总动脉结扎和缺氧治疗，并给予EPCs或EC-pEPCs治疗，然后在第6周评估血管生成和髓鞘形成以及认知结果。结果EPCs能增强内皮功能，减少OPC凋亡。同时证实OGD-EC-CM诱导EPCs中CXCL12表达增加，CXCL12-CXCR4轴是关键信号通路，CXCR4敲低可减轻EPCs对OPCs的抗凋亡作用。在体内，WMI大鼠EPCs数量和CXCL12蛋白水平显著升高。与EPCs相比，EC-pEPCs显著降低了新生大鼠WMI模型的OPC凋亡，增加了胼胝体的血管密度和髓鞘形成，改善了学习和记忆缺陷。结论在新生大鼠WMI模型中，sec - pepcs通过CXCL12-CXCR4轴更有效地促进少血管重构和髓鞘形成。
BackgroundOligovascular niche mediates interactions between cerebral endothelial cells and oligodendrocyte precursor cells (OPCs). Disruption of OPC-endothelium trophic coupling may aggravate the progress of cerebral white matter injury (WMI) because endothelial cells could not provide sufficient support under diseased conditions. Endothelial progenitor cells (EPCs) have been reported to ameliorate WMI in the adult brain by boosting oligovascular remodeling. It is necessary to clarify the role of the conditioned medium from hypoxic endothelial cells preconditioned EPCs (EC-pEPCs) in WMI since EPCs usually were recruited and play important roles under blood-brain barrier disruption. Here, we investigated the effects of EC-pEPCs on oligovascular remodeling in a neonatal rat model of WMI.MethodsIn vitro, OPC apoptosis induced by the conditioned medium from oxygen-glucose deprivation-injured brain microvascular endothelial cells (OGD-EC-CM) was analyzed by TUNEL and FACS. The effects of EPCs on EC damage and the expression of cytomokine C-X-C motif ligand 12 (CXCL12) were examined by western blot and FACS. The effect of the CM from EC-pEPCs against OPC apoptosis was also verified by western blot and silencing RNA. In vivo, P3 rat pups were subjected to right common carotid artery ligation and hypoxia and treated with EPCs or EC-pEPCs at P7, and then angiogenesis and myelination together with cognitive outcome were evaluated at the 6th week.ResultsIn vitro, EPCs enhanced endothelial function and decreased OPC apoptosis. Meanwhile, it was confirmed that OGD-EC-CM induced an increase of CXCL12 in EPCs, and CXCL12-CXCR4 axis is a key signaling since CXCR4 knockdown alleviated the anti-apoptosis effect of EPCs on OPCs. In vivo, the number of EPCs and CXCL12 protein level markedly increased in the WMI rats. Compared to the EPCs, EC-pEPCs significantly decreased OPC apoptosis, increased vascular density and myelination in the corpus callosum, and improved learning and memory deficits in the neonatal rat WMI model.ConclusionsEC-pEPCs more effectively promote oligovascular remodeling and myelination via CXCL12-CXCR4 axis in the neonatal rat WMI model.
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影响因子：
6
作者：
Li, Yaning;Tang, Guanghui;Wang, Yongting
通讯作者：
Wang, Yongting
影响因子：
4.7
作者：
Hayakawa K;Miyamoto N;Seo JH;Pham LD;Kim KW;Lo EH;Arai K
通讯作者：
Arai K
影响因子：
5.3
作者：
Arai, Ken;Lo, Eng H.
通讯作者：
Lo, Eng H.
影响因子：
8.3
作者：
Jickling, Glen;Salam, Abdul;Camicioli, Richard
通讯作者：
Camicioli, Richard
影响因子：
--
作者：
Egawa N;Lok J;Arai K
通讯作者：
Arai K