Neointima Formation and Thrombus Organization after Coil and Stent Treatment Is Mediated by Cell Migration from the Adjacent Vital Vessel Wall in Rat Sidewall Aneurysms

Aim: The biological response of endovascular intracranial aneurysm treatment is to initiate intraluminal thrombus formation and to stimulate growth of a neointima which separates the aneurysm dome from the circulation. These processes are mediated by cells, as, that is, vascular smooth muscle cells (SMC). As of yet it remains unclear if these SMC are mainly recruited from the aneurysm wall, if they originate from progenitor cells or whether they migrate from the parent artery.

Methods: In this experimental study in n = 20 male Sprague Dawley rats aneurysms were transplanted on the abdominal aorta and treated with intra-aneurysmal coil placement. Of them, in n = 10 cases decellularized wild-type aneurysm were sutured on a green-fluorescent positive (GFP+) rat and in n = 10 cases GFP+ aneurysms were sutured on wild-type rats. Additionally, in n = 20 male Lewis rats aneurysm were treated with a stent. In n = 10 cases of them decellularized wild-type aneurysms were sutured on GFP+ animals and in n = 10 cases GFP+ aneurysms were sutured on wild-type animals. On follow-up examinations after 3, 7, 14, 21, and 28 days, aneurysms were evaluated on perfusion status and tissues macroscopically and histologically examined.

Results: Sequential arrangement over time showed progressive neointima formation with increasing neointima thickness and gradually advancing thrombus formation. Qualitative assessment of histology revealed migration of aneurysm wall cells into the thrombus. In GFP+ animals, GFP+ cells were found along the neointima, in the aneurysm wall and inside the organizing thrombus.

Conclusion: Neointima formation and thrombus organization are concurrent processes in aneurysm healing after endovascular treatment. Distribution of GFP+ cells in coiled and in stent treated aneurysms suggests organizing cells to origin from the adjacent vessel. These cells migrate into the aneurysm wall, into the thrombus and form the neointima.