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自体脂肪来源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。

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

机构信息

Applied Neuroradiology Laboratory, Mayo Clinic, Rochester, Minnesota, USA.

Department of Interventional Neuroradiology, NEURI Center, Le Kremlin-Bicetre, France.

出版信息

J Neurointerv Surg. 2018 Jan;10(1):60-65. doi: 10.1136/neurintsurg-2016-012867. Epub 2017 Jan 11.

Abstract

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. χ 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 μm vs 31 810 μm, 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.

摘要

目的

被圈闭的动脉瘤常常发生长期闭塞失败,这可能是由于瘤腔内愈合不良和瘤颈处内皮化不足所致。本研究旨在确定将自体间充质干细胞(MSCs)附着在铂金线圈上是否会改善弹性蛋白酶诱导的兔动脉瘤模型中的愈合反应。

材料和方法

在机构动物护理和使用委员会的批准下,在兔体内创建动脉瘤,并使用对照铂金线圈(Axium;美敦力)(n=6)或体外种植自体脂肪组织 MSCs 的线圈(n=7)进行栓塞。栓塞后 1 个月通过血管造影评估动脉瘤闭塞情况。大体成像分析组织学样本,并根据 H&E 染色的颈部和瘤顶愈合情况进行分级。使用胶原总面积比评估纤维化。使用 CD31 免疫组化定量分析颈部内皮化。使用 χ2 和学生 t 检验比较组间差异。

结果

MSC 组的愈合评分(11.5 比 8.0,p=0.019)、纤维化比例(10.3 比 0.13,p=0.006)和内皮化(902262μm 比 31810μm,p=0.041)均显著更高。MSC 组显示出明显的细胞增殖和血栓组织形成,有一个连续的膜桥接在动脉瘤颈部。MSC 组的血管造影稳定或进行性闭塞率明显低于对照组(0.00,95%置信区间 0.00 至 0.41)(p=0.02)。

结论

附着在铂金线圈上的自体 MSCs 显著改善了组织学愈合,因为它们导致动脉瘤囊内的颈部内皮化和胶原基质形成得到改善。

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