Parent artery-initiated and stent-mediated neointima formation in a rat saccular side wall model

Abstract

BackgroundUnlike clipping that forms an immediate barrier of blood flow into intracranial aneurysms, endovascular treatments rely on thrombus organization and neointima formation. Therefore, a continuous endothelial cell layer is crucial to prevent blood flow in the former aneurysm. This study investigates the origin of endothelial cells in the neointima of endovascular treated aneurysms, specifically whether cells from the parent artery play a role in neointima formation.MethodsIn male rats, decellularized and vital side wall aneurysms were treated by coil (n=16) or stent embolization (n=15). The cell tracer CM-Dil dye was injected into the clamped aorta before aneurysm suture to mark initial endothelial cells in the parent artery and enable tracking of their proliferation during follow-up. Aneurysms were analyzed for growth, thrombus formation, and recurrence. Histological evaluation followed with cell counts for specific regions-of-interest.ResultsDuring follow-up, none of the 31 aneurysms ruptured. Macroscopic residual perfusion was observed in 12/16 rats after coiling and in 1/15 after stenting. Amounts of CM-Dil +cells in coiled versus stented decellularized aneurysms significantly decreased in the thrombus on day 7 (p=0.01) and neointima on day 21 (p=0.04). For vital aneurysms, the number of CM-Dil +cells in the neointima on day 21 showed no significant difference.ConclusionsHealing patterns were worse in coil-treated than stent-treated aneurysms. Cell migration forming a neointima seemed mainly dependent on the adjacent vessel in decellularized aneurysms, but appeared buoyed by recruitment from aneurysm wall cells in vital aneurysms. Therefore, a cell-rich parent artery might be crucial.

Aneurysm healing after endovascular treatment in the Helsinki sidewall aneurysm model: a systematic review

“…Complete aneurysm occlusion was observed in 93.3% (14/15) and 25% (4/16) of stented and coiled aneurysms, respectively (table 1). 10 Somewhat in contrast to the results of Grüter and colleagues, no difference in neointimal fluorescence signal was observed in vital aneurysms treated with coiling versus stenting 9 10. In decellularized aneurysms, however, greater neointimal signal was observed in stented compared with coiled aneurysms,10 suggesting that mural cellularity may influence the need for parent artery cell contribution to neointimal formation.…”

“…Considering the superior degree of observed neointimal formation in stented relative to coiled aneurysms, these findings may explain the superior rates of sustained aneurysm occlusion after stent coiling noted in clinical studies 28. In a follow-up study by the same group, Wanderer and colleagues investigated the effect of aneurysm decellularization on the relative contributions of mural and parent artery cells to neointima formation after coiling versus stenting 10. Similar to prior experiments, 2 mm × 2 cm coils and 2 mm × 6 mm stents were implanted.…”

“…The results presented in this systematic review provide a measure of aneurysm occlusion rates after endovascular treatment of the Helsinki sidewall aneurysm with different devices (table 1), which may be useful information for future studies attempting to demonstrate improved efficacy of one device over another. Endovascular coiling, particularly of decellularized aneurysms, was consistently associated with low rates of aneurysm occlusion,9 10 17 and thus the Helsinki model appears to be an excellent model for testing and improving emerging coiling technology. It should be noted, however, that coil packing density in the presented studies was quite low, which may have contributed to the low rates of aneurysm occlusion after coiling.…”

“…It should be noted, however, that coil packing density in the presented studies was quite low, which may have contributed to the low rates of aneurysm occlusion after coiling. In contrast, regardless of aneurysm cellularity, both stent and flow diverter placement across the aneurysm neck were associated with fairly high rates of aneurysm occlusion (table 1),5 9 10 34 which may complicate comparative analyses of different devices. Ultimately, modifications to the model may be necessary to test the relative efficacy of different stent technologies.…”

“…Moreover, this model represents a relatively inexpensive and reproducible alternative to large animal aneurysm models, and importantly allows the placement of both standard and experimental endovascular devices within the created aneurysm at the time of aneurysm formation 5–7. After an interval period, blood flow into the aneurysm can be assessed by fluorescence angiography,8 and on animal sacrifice, histologic analyses can be performed to quantify the degree of aneurysm healing after endovascular treatment 9 10…”