Frösen Juhana, Marjamaa Johan, Myllärniemi Marjukka, Abo-Ramadan Usama, Tulamo Riikka, Niemelä Mika, Hernesniemi Juha, Jääskeläinen Juha
Neurosurgery Research Group, Biomedicum Helsinki, and Transplantation Laboratory, University of Helsinki, Helsinki, Finland.
Neurosurgery. 2006 May;58(5):936-44; discussion 936-44. doi: 10.1227/01.NEU.0000210260.55124.A4.
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.
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.
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).
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.
人类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。骨髓来源的祖细胞可能参与这些过程，但其在人类囊状脑动脉瘤和实验性动脉瘤模型中的作用仍不清楚。
用同基因胸主动脉端侧移植至Wistar大鼠（n = 14）、C57/B6小鼠（n = 13）、ApoE小鼠（n = 7）、表达报告基因的ROSA小鼠（n = 7）以及骨髓标记小鼠（ROSA [n = 12]或绿色荧光蛋白 [n = 3]）的腹主动脉来构建实验性囊状动脉瘤。采用磁共振成像或血管造影术监测实验性动脉瘤的通畅情况。用组织学和免疫组织化学方法研究血栓机化和新生内膜形成，用X-gal染色和共聚焦显微镜研究新生内膜细胞的起源。
实验性动脉瘤形成了新生内膜增生或机化血栓的腔内垫，在第一周的后期这些腔内垫变得更厚并部分阻塞管腔。报告基因小鼠（ROSA）显示，42%至81%（中位数为58%）的新生内膜增生/机化血栓源自实验性动脉瘤壁。仅在15只小鼠中的5只发现了骨髓来源的新生内膜细胞（范围为每切片11 - 73个细胞；在总共2000 - 6000个壁细胞中，中位数为22个细胞）。
血栓机化或新生内膜细胞大多源自实验性动脉瘤壁，骨髓的贡献较小。在人类囊状脑动脉瘤中，骨髓来源的新生内膜细胞的贡献可能更重要，应与用于开发血管内治疗的其他实验模型中的情况进行比较。
