Endothelial progenitor cell transplantation restores vascular injury in mice after whole-brain irradiation
Endothelial progenitor cell transplantation restores vascular injury in mice after whole-brain irradiation
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DOI：
10.1016/j.brainres.2020.147005
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发表时间：
2020-11-01
期刊：
影响因子：
2.9
通讯作者：
Huang, Haiwei
中科院分区：
文献类型：
--
作者：
Huang, Xurui;Li, Minping;Huang, Haiwei
血管损伤在放射性脑损伤的发病机制中起着重要作用。内皮祖细胞（Endothelial progenitor cells，EPCs）具有维持和修复血管内皮功能的作用，已成为治疗脑血管疾病的一种有前景的方法。然而，内皮祖细胞移植是否对脑损伤起到保护作用尚未完全阐明。因此，本研究探讨骨髓来源的EPC移植在全脑照射（WBI）小鼠模型中的作用。将小鼠分为对照组、照射组和EPCs组。照射后一周，将磷酸盐缓冲盐水或EPC静脉注射到小鼠中，并在注射后八周分析脑。流式细胞术表明，辐射导致外周血EPC计数显着减少，然而，EPC移植导致循环EPCs显着增加。活体双光子成像和蛋白质印迹表明，EPC移植逆转辐射的影响，通过降低血脑屏障通透性和增加紧密连接蛋白在脑中的表达。免疫荧光染色显示EPCs组脑微血管密度高于照射组。因此，EPC移植可以恢复由WBI引起的对血脑屏障、紧密连接和脑毛细血管密度的损伤。这些结果突出了EPC移植对RBI诱导的血管损伤的潜在有益作用。
Vascular damage plays an important role in the pathogenesis of radiation-induced brain injury (RBI). Endothelial progenitor cells (EPCs) are responsible for maintaining and repairing endothelial function, and have become a promising method for the treatment of cerebrovascular diseases. However, whether EPC transplantation plays a protective role in RBI has not been fully elucidated. Therefore, the present study investigated the effects of bone marrow-derived EPC transplantation in a whole-brain irradiation (WBI) mouse model. Mice were divided into the three groups: control group, irradiation group and EPCs group. Phosphate buffered saline or EPCs were intravenously injected into mice one week after irradiation, and brains were analyzed eight weeks after injection. Flow cytometry demonstrated that irradiation led to a significant reduction in the peripheral blood EPC count; however, EPC transplantation led to a significant increase in the circulating EPCs. Intravital two-photon imaging and western blotting demonstrated that EPC transplantation reversed the effects of irradiation by decreasing blood-brain barrier permeability and increasing the expression of tight junction proteins in the brain. Additionally, immunofluorescence staining revealed that the brain microvascular density was higher in the EPCs group than the irradiation group. Therefore, EPC transplantation may restore damage caused by WBI to the blood-brain barrier, tight junctions, and cerebral capillary density. These results highlight the potential beneficial effects of EPC transplantation on vascular damage induced by RBI.