Contribution of mural and bone marrowderived neointimal cells to thrombus organization and wall remodeling in a microsurgical murine saccular aneurysm model
Contribution of mural and bone marrowderived neointimal cells to thrombus organization and wall remodeling in a microsurgical murine saccular aneurysm model
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DOI：
10.1227/01.neu.0000210260.55124.a4
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发表时间：
2006-05-01
期刊：
影响因子：
4.8
通讯作者：
Jääskeläinen, J
中科院分区：
文献类型：
--
作者：
Frösen, J;Marjamaa, J;Jääskeläinen, J
目的：球囊状脑动脉瘤的血管内闭塞治疗可能因血栓再通和新生内膜形成不完全而失败。方法：将Wistar大鼠(n=14)、C57/B6小鼠(n=13)、ApoE小鼠(n=7)、ROSA报告基因表达的小鼠(n=7)和标记骨髓(ROSA[n=12]或绿色荧光蛋白[n=3])小鼠建立囊状动脉瘤模型。用磁共振成像或血管造影术监测实验性动脉瘤的通畅性。用组织学和免疫组织化学方法观察血栓组织和新生内膜的形成，用X-Gal染色和共聚焦显微镜观察新生内膜细胞的来源。结果：在实验的第一周，实验性动脉瘤形成新的内膜增生或机化血栓形成，增厚并部分闭塞管腔。报告基因小鼠(ROSA)显示，42~81(中位数，58%)的新生内膜增生/机化血栓形成来自于实验性动脉瘤壁。15只小鼠中仅5只有骨髓来源的新生内膜细胞(每张切片11-73个，平均22个细胞)。结论：血栓组织化或新生内膜细胞主要来源于实验性动脉瘤壁，骨髓的贡献很小。在人类囊状大脑动脉动脉瘤中，骨髓来源的新生内膜细胞的贡献可能更重要，应该与用于开发血管内治疗的其他实验模型进行比较。
OBJECTIVE: Endovascular occlusive therapy of human saccular cerebral artery aneurysms may fail because of thrombus recanalization and incomplete neointima formation. Bone marrow-derived progenitor cells may contribute to these processes, but their role in human saccular cerebral artery aneurysms and experimental aneurysm models remains unclear.METHODS: Experimental saccular aneurysms were constructed from syngeneic thoracic aortas transplanted end-to-side to the abdominal aorta of Wistar rats (n = 14), C57/B6 mice (n = 13), ApoE mice (n = 7), reporter gene expressing ROSA mice (n = 7), and mice with labeled bone marrow (ROSA [n = 12] or green fluorescent protein [n = 3]). Magnetic resonance imaging or angiography was used to monitor patency of the experimental aneurysms. Histology and immunohistochemistry were used to study thrombus organization and neointima formation and X-gal staining and confocal microscopy to study the origin of neointimal cells.RESULTS: Experimental aneurysms developed luminal pads of neointimal hyperplasia or organizing thrombosis that became thicker and occluded partly the lumen at later time points during the first week. Reporter gene mice (ROSA) revealed that 42 to 81 (median, 58%) of neointimal hyperplasia/organizing thrombosis was derived from the experimental aneurysm wall. Bone marrow-derived neointimal cells were found in only 5 of 15 mice (range, 11-73 per section; a median of 22 cells among a total of 2000-6000 wall cells).CONCLUSION: Thrombus organizing or neointimal cells were mostly derived from the experimental aneurysm wall, with only a minor contribution from the bone marrow. In human saccular cerebral artery aneurysms, the contribution of bone marrow-derived neointimal cells might be more important and should be compared with that found in other experimental models used to develop endovascular therapies.