Department of Neurosurgery, The General Hospital of Shenyang Military Region, No. 83 Wenhua Road, Shenyang, 110840, Liaoning, People's Republic of China.
J Mater Sci Mater Med. 2014 May;25(5):1357-66. doi: 10.1007/s10856-014-5157-9. Epub 2014 Jan 28.
We aimed to evaluate whether adipose-derived mesenchymal stem cells (ADMSCs) that were transplanted via internal carotid can improve the neurological function after acute ischemic stroke and explore the underlying mechanisms. Total 40 adult Sprague-Dawley rats were subjected to transient (1.5 h) middle cerebral artery occlusion (MCAo) to induce ischemia/reperfusion injury. These rats were randomly divided into two groups with 20 ones in each group, which were intracarotid-injected with autologous ADMSCs (2.0 × 10(6)) and saline (control) at day 3 after MCAo, respectively. Behavioral tests (adhesive-removal and modified neurological severity score) were performed before and after MCAo. Histology was used to evaluate the ischemia lesion volume and pathological changes. The apoptosis and astroglial reactivity were determined by TUNEL and glial fibrillary acidic protein (GFAP) staining, respectively. Besides, we applied immunofluorescence to identify the distribution of ADMSCs and the neural makers (NeuN and GFAP) expressed by them under confocal microscope. Significant improvement of neurological deficits was observed in rats transplanted with ADMSCs when compared to controls. But there was no obvious difference on ischemia lesion volume between these two groups. The injected ADMSCs migrated to the brain infarct region and mainly localized in the ischemic core and boundary zone of the lesion, which can express NeuN and GFAP in the brain. In addition, autologous transplantation of ADMSCs significantly attenuated astroglial reactivity, inhibited cellular apoptosis and promoted cellular proliferation. Our data indicated that intracarotid transplantation of autologous ADMSCs had the potential therapeutic application for ischemic stroke.
我们旨在评估经颈内动脉移植的脂肪间充质干细胞（ADMSCs）是否可以改善急性缺血性脑卒中后的神经功能，并探讨其潜在机制。总共 40 只成年 Sprague-Dawley 大鼠接受短暂（1.5 小时）大脑中动脉闭塞（MCAo）以诱导缺血/再灌注损伤。这些大鼠随机分为两组，每组 20 只，分别在 MCAo 后第 3 天经颈内动脉注射自体 ADMSCs（2.0×10(6)）和生理盐水（对照组）。在 MCAo 前后进行行为测试（粘取和改良神经功能缺损评分）。组织学用于评估缺血损伤体积和病理变化。通过 TUNEL 和胶质纤维酸性蛋白（GFAP）染色分别测定细胞凋亡和星形胶质细胞反应性。此外，我们应用免疫荧光在共聚焦显微镜下识别 ADMSCs 的分布及其表达的神经标志物（NeuN 和 GFAP）。与对照组相比，移植 ADMSCs 的大鼠神经功能缺损明显改善。但两组间缺血损伤体积无明显差异。注射的 ADMSCs 迁移到脑梗死区域，主要定位于损伤的缺血核心和边界区，在脑内可表达 NeuN 和 GFAP。此外，自体移植 ADMSCs 可显著减轻星形胶质细胞反应性，抑制细胞凋亡，促进细胞增殖。我们的数据表明，经颈内动脉自体移植 ADMSCs 具有缺血性脑卒中的潜在治疗应用价值。
