Gao Yuyuan, Wang Qiujing, Cui Xubo, Liu Yaqi, Zheng Tao, Chen Chengwei, Sun Chengmei, Huang Shuyun, Wang Xin, Liu Yanchao, Jiang Xiaodan, Zeng Chi, Quan Daping
Department of Neurosurgery, Zhujiang Hospital, The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University Guangzhou City, Guangdong Province, P.R. China.
Scholl of Chemistry and Chemical Engineering, Sun Yat-Sen University Guangzhou City, Guangdong Province, P.R. China.
Int J Clin Exp Pathol. 2014 Dec 1;7(12):8366-80. eCollection 2014.
This study is to test the efficacy of stromal cell-derived factor-1α (SDF-1α)-coated coils together with endothelial progenitor cells (EPCs) transplantation in occluding aneurysms. Bone marrow-derived EPC surface markers were analyzed using flow cytometry. The migratory function of EPCs in response to SDF-1α was evaluated using a modified Boyden chamber assay. Capillary-like tube formation was assessed using Matrigel gel. Coil morphologies before and after coating with SDF-1α were observed under a scanning electron microscope. The level of SDF-1α in supernatants was measured by ELISA. Sprague-Dawley rats were randomly allocated into five groups. Histological analysis was performed on days 14 and 28 after coil implantation. The bone marrow-EPCs could express CD133, CD34, and VEGFR-2 and form tubule-like structures in vitro. Migratory ability of EPCs in the presence of SDF-1α-coated coils was similar to that in the presence of 5 ng/ml SDF-1α gradient. Sustained release of SDF-1α was achieved using silk fibroin as a carrier. In SDF-1α-coated coils + EPCs transplantation group, a well-organized fibrous tissue bridging the orifice of aneurysms was shown on days 14 and 28. On day 28, tissue organization was greater in the SDF-1α-coated coils group than in the unmodified coils group. Immunofluorescence showed α-smooth muscle actin-positive cells in organized tissue in sacs. Combined treatment with SDF-1α-coated coils and EPCs transplantation is a safe and effective treatment for rat aneurysms. This may provide a new strategy for endovascular therapy following aneurysmal subarachnoid hemorrhage.
本研究旨在测试基质细胞衍生因子-1α（SDF-1α）包被的弹簧圈联合内皮祖细胞（EPCs）移植封堵动脉瘤的疗效。采用流式细胞术分析骨髓来源的EPC表面标志物。使用改良的Boyden小室试验评估EPCs对SDF-1α的迁移功能。使用基质胶评估毛细血管样管形成。在扫描电子显微镜下观察SDF-1α包被前后弹簧圈的形态。通过ELISA测量上清液中SDF-1α的水平。将Sprague-Dawley大鼠随机分为五组。在弹簧圈植入后第14天和第28天进行组织学分析。骨髓EPCs可表达CD133、CD34和VEGFR-2，并在体外形成管状结构。在存在SDF-1α包被的弹簧圈的情况下，EPCs的迁移能力与存在5 ng/ml SDF-1α梯度时相似。使用丝素蛋白作为载体实现了SDF-1α的持续释放。在SDF-1α包被的弹簧圈+EPCs移植组中，在第14天和第28天显示有组织良好的纤维组织桥接动脉瘤口。在第28天，SDF-1α包被的弹簧圈组的组织化程度高于未修饰弹簧圈组。免疫荧光显示囊内有组织的组织中α平滑肌肌动蛋白阳性细胞。SDF-1α包被的弹簧圈与EPCs移植联合治疗对大鼠动脉瘤是一种安全有效的治疗方法。这可能为动脉瘤性蛛网膜下腔出血后的血管内治疗提供一种新策略。
