Autologous adipose-derived mesenchymal stem cells improve healing of coiled experimental saccular aneurysms: an angiographic and histopathological study

自体脂肪间充质干细胞改善实验性囊状动脉瘤的愈合:血管造影和组织病理学研究

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作者:Aymeric Rouchaud, Waleed Brinjikji, Daying Dai, Yong-Hong Ding, Tina Gunderson, Dana Schroeder, Laurent Spelle, David F Kallmes, Ramanathan Kadirvel

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.

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.

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

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.

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