Department of Neurological Surgery, University of Washington, Seattle, WA, USA.
Stroke & Applied Neuroscience Center, University of Washington, Seattle, WA, USA.
Ann Biomed Eng. 2024 Dec;52(12):3253-3263. doi: 10.1007/s10439-024-03591-0. Epub 2024 Aug 2.
Flow diverting stents (FDS) are used to treat cerebral aneurysms, by promoting thrombosis and occlusion of the aneurysm sac. However, retreatment is required in some cases, and the biologic basis behind treatment outcome is not known. The goal of this study was to understand how changes in hemodynamic flow after FDS placement affect aneurysmal endothelial cell (EC) activity.
Three-dimensional models of patient-specific aneurysms were created to quantify the EC response to FDS placement. Computational fluid dynamic simulations were used to determine the hemodynamic impact of FDS. Two identical models were created for each patient; into one a FDS was inserted. Each model was then populated with human carotid ECs and subjected to patient-specific pulsatile flow for 24 h. ECs were isolated from aneurysm dome from each model and bulk RNA sequencing was performed.
Paired untreated and treated models were created for four patients. Aneurysm dome EC analysis revealed 366 (2.6%) significant gene changes between the untreated and FDS conditions, out of 13909 total expressed genes. Gene set enrichment analysis of the untreated models demonstrated enriched gene ontology terms related to cell adhesion, growth/tensile activity, cytoskeletal organization, and calcium ion binding. In the FDS models, enriched terms were related to cellular proliferation, ribosomal activity, RNA splicing, and protein folding.
Treatment of cerebral aneurysms with FDS induces significant EC gene transcription changes related to aneurysm hemodynamics in patient-specific in vitro 3D-printed models subjected to pulsatile flow. Further investigation is needed into the relationship between transcriptional change and treatment outcome.
血流导向装置（FDS）用于通过促进动脉瘤囊的血栓形成和闭塞来治疗脑动脉瘤。然而，在某些情况下需要进行再治疗，并且不知道治疗结果的生物学基础。本研究的目的是了解 FDS 放置后血流动力学变化如何影响动脉瘤内皮细胞（EC）的活性。
创建了患者特定动脉瘤的三维模型，以量化 FDS 放置后 EC 的反应。使用计算流体动力学模拟来确定 FDS 的血流动力学影响。为每个患者创建了两个相同的模型；一个模型中插入了 FDS。然后，每个模型都填充了人颈动脉 EC，并对其进行了 24 小时的患者特定脉动流。从每个模型的动脉瘤穹顶中分离出 EC，并进行批量 RNA 测序。
为四个患者创建了配对的未治疗和治疗模型。动脉瘤穹顶 EC 分析显示，在未治疗和 FDS 条件之间有 366 个（2.6%）显著基因变化，而在 13909 个总表达基因中。未治疗模型的基因集富集分析表明，与细胞粘附、生长/拉伸活性、细胞骨架组织和钙离子结合相关的基因本体术语丰富。在 FDS 模型中，富集的术语与细胞增殖、核糖体活性、RNA 剪接和蛋白质折叠有关。
在经受脉动流的患者特异性 3D 打印模型中，FDS 治疗脑动脉瘤会引起与动脉瘤血流动力学相关的显著 EC 基因转录变化。需要进一步研究转录变化与治疗结果之间的关系。
