Gunderson, Tina

Background Intracranial aneurysms represent a significant health concern and are poorly understood despite decades of research. Our study focused on understanding temporal patterns of endothelial cell distribution in different spatial locations within the aneurysm early after creation in a rabbit model. Methods Elastase induced saccular aneurysms were created in rabbits and harvested on day 1 (n=3) and after 2 (n=5), 4 (n=4), 8 (n=5), and 12 (n=6) weeks. Sham operated controls (n=3) were harvested on the same day. Aneurysm and control tissue samples were subjected to en face whole mount CD31 staining for endothelial cells. Semiquantitative scoring was performed on the basis of endothelial coverage of the vessel wall (proximal, middle, and distal portions of the aneurysm dome). Mixed effects models were used to assess the effect of time and aneurysm section on endothelial coverage. Results Aneurysmal segments were near completely de-endothelialized at 4 and 8 weeks but had re-endothelialized by 12 weeks. Compared with controls, aneurysms at all time points showed decreased endothelialization, but the difference was only significant compared with the 4 and 8 week groups. Both time (P=0.03) and aneurysm section (P=0.07) were significantly associated with the degree of endothelialization. Proximal locations showed increased endothelialization compared with distal locations (P=0.03). Conclusion In experimental aneurysms of rabbits, endothelial cells regress during the first month after creation, followed by ascending re-endothelialization that stays incomplete. These findings suggest that re-population of endothelial cells comes from resident cells in the adjacent parent artery and that deranged hemodynamics may affect full reconstitution of endothelial cells long term.

Purpose Long-term occlusion of coiled aneurysms frequently fails, probably because of poor intrasaccular healing and inadequate endothelialization across the aneurysm neck. The purpose of this study was to determine if attachment of autologous mesenchymal stem cells (MSCs) to platinum coils would improve the healing response in an elastase-induced aneurysm model in rabbits. Materials and methods With approval from the institutional animal care and use committee, aneurysms were created in rabbits and embolized with control platinum coils (Axium; Medtronic) (n=6) or coils seeded ex vivo with autologous adipose-tissue MSCs (n=7). Aneurysmal occlusion after embolization was evaluated at 1 month with angiography. Histological samples were analyzed by gross imaging and graded on the basis of neck and dome healing on H&E staining. Fibrosis was evaluated using a ratio of the total area presenting collagen. Endothelialization of the neck was quantitatively analyzed using CD31 immunohistochemistry. χ2 and Student's t-test were used to compare groups. Results Healing score (11.5 vs 8.0, p=0.019), fibrosis ratio (10.3 vs 0.13, p=0.006) and endothelialization (902 262 μm2 vs 31 810 μm2, p=0.041) were significantly greater in the MSC group. The MSC group showed marked cellular proliferation and thrombus organization, with a continuous membrane bridging the neck of the aneurysm. Angiographic stable or progressive occlusion rate was significantly lower in the MSC group (0.00, 95% CI 0.00 to 0.41) compared with controls (0.67, 95% CI 0.22 to 0.96) (p=0.02). Conclusions Autologous MSCs attached to platinum coils significantly improve histological healing, as they result in improved neck endothelialization and collagen matrix formation within the aneurysm sac.