Department of Neurosurgery (B.E.G., S.W., F.S., G.B., L.A., E.N., D.C., J.F., S.M.), Kantonsspital Aarau, Switzerland.
Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.
Stroke. 2021 Mar;52(3):1043-1052. doi: 10.1161/STROKEAHA.120.032255. Epub 2021 Jan 28.
Endovascular aneurysm treatment relies on a biological process, including cell migration for thrombus organization and growth of a neointima. To better understand aneurysm healing, our study explores the origin of neointima-forming and thrombus-organizing cells in a rat saccular sidewall aneurysm model.
Saccular aneurysms were transplanted onto the abdominal aorta of male Lewis rats and endovascularly treated with coils (n=28) or stents (n=26). In 34 cases, GFP+ (green fluorescent protein)-expressing vital aneurysms were sutured on wild-type rats, and in 23 cases, decellularized wild-type aneurysms were sutured on GFP+ rats. Follow-up at 3, 7, 14, 21, and 28 days evaluated aneurysms by fluorescence angiography, macroscopic inspection, and microscopy for healing and inflammation status. Furthermore, the origin of cells was tracked with fluorescence histology.
In animals with successful functional healing, histological studies showed a gradually advancing thrombus organization over time characterized by progressively growing neointima from the periphery of the aneurysm toward the center. Cell counts revealed similar distributions of GFP+ cells for coil or stent treatment in the aneurysm wall (54.4% versus 48.7%) and inside the thrombus (20.5% versus 20.2%) but significantly more GFP+ cells in the neointima of coiled (27.2 %) than stented aneurysms (10.4%; =0.008).
Neointima formation and thrombus organization are concurrent processes during aneurysm healing. Thrombus-organizing cells originate predominantly in the parent artery. Neointima formation relies more on cell migration from the aneurysm wall in coiled aneurysms but receives greater contributions from cells originating in the parent artery in stent-treated aneurysms. Cell migration, which allows for a continuous endothelial lining along the parent artery's lumen, may be a prerequisite for complete aneurysm healing after endovascular therapy. In terms of translation into clinical practice, these findings may explain the variability in achieving complete aneurysm healing after coil treatment and the improved healing rate in stent-assisted coiling.
血管内动脉瘤治疗依赖于一个生物学过程，包括细胞迁移以形成血栓和新生内膜的生长。为了更好地了解动脉瘤的愈合过程，我们的研究探索了在大鼠囊状侧壁动脉瘤模型中，新生内膜形成和血栓形成细胞的来源。
将囊状动脉瘤移植到雄性 Lewis 大鼠的腹主动脉中，并通过血管内线圈（n=28）或支架（n=26）进行治疗。在 34 例情况下，将表达 GFP+（绿色荧光蛋白）的有活力的动脉瘤缝合在野生型大鼠上，在 23 例情况下，将去细胞化的野生型动脉瘤缝合在 GFP+大鼠上。在第 3、7、14、21 和 28 天通过荧光血管造影、大体检查和显微镜检查评估动脉瘤的愈合和炎症状态。此外，通过荧光组织学追踪细胞的来源。
在功能愈合成功的动物中，组织学研究显示随着时间的推移，血栓逐渐组织化，表现为从动脉瘤的外周向中心逐渐生长的新生内膜。细胞计数显示，线圈或支架治疗在动脉瘤壁（54.4%比 48.7%）和血栓内（20.5%比 20.2%）的 GFP+细胞分布相似，但在 coil 处理的动脉瘤中 GFP+细胞在新生内膜中的比例更高（27.2%）比支架处理的动脉瘤（10.4%）高（=0.008）。
新生内膜形成和血栓组织化是动脉瘤愈合过程中的并发过程。血栓形成细胞主要来源于母动脉。在 coil 处理的动脉瘤中，新生内膜形成更多地依赖于来自动脉瘤壁的细胞迁移，但在支架处理的动脉瘤中，来自母动脉的细胞贡献更大。细胞迁移可以使母动脉管腔的内皮连续，这可能是血管内治疗后完全愈合动脉瘤的前提。就转化为临床实践而言，这些发现可以解释 coil 治疗后完全愈合动脉瘤的变异性以及支架辅助 coil 治疗中愈合率的提高。
