Bone marrow stromal cell transplantation enhances recovery of motor function after lacunar stroke in rats
Bone marrow stromal cell transplantation enhances recovery of motor function after lacunar stroke in rats
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DOI：
10.55782/ane-2013-1942
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发表时间：
2013-01-01
影响因子：
1.4
通讯作者：
Kuroda, Satoshi
中科院分区：
文献类型：
--
作者：
Shichinohe, Hideo;Yamauchi, Tomohiro;Kuroda, Satoshi
本研究旨在阐明当立体定向移植到脑内时，骨髓基质细胞(BMSCs)是否能显著改善腔隙卒中后的功能结局。将Na/K-ATPase泵抑制剂哇巴因立体定向注射到Wistar大鼠右侧纹状体内。1周后，将超顺磁性氧化铁(SPIO)标记的大鼠骨髓间充质干细胞(n=7)或载体(n=8)立体定向移植到左侧纹状体内。采用旋转棒试验，通过实验对患者的运动功能进行系列评定。用7.0T磁共振连续监测BMSCs在宿主脑内的迁移情况。在哇巴因注射后7周，即骨髓间充质干细胞移植后6周进行组织学观察。哇巴因注射导致右侧纹状体出现可复制的局灶性损害，在整个实验过程中导致持续的运动功能障碍。骨髓间充质干细胞移植明显促进哇巴因注射后运动功能的恢复。磁共振成像显示，骨髓间充质干细胞侵袭性地向病变方向迁移，通过胼胝体。组织学分析支持MRI所见。骨髓间充质干细胞能明显促进双侧脑室下区神经发生。部分神经元或星形细胞表型分布于新皮质、下丘脑室旁区、穹窿体区和笔状损伤区。这些发现有力地表明，当在临床相关的时间进行立体移植时，骨髓间充质干细胞可能对腔隙卒中起到治疗作用。
This study was aimed to clarify if the bone marrow stromal cells (BMSCs) significantly improve functional outcome after lacunar stroke when stereotactically transplanted into the brain. Ouabain, a Na/K ATPase pump inhibitor, was stereotactically injected into the right striatum of Wistar rats. One week later, the superparamagnetic iron oxide (SPIO)-labeled rat BMSCs (n=7) or vehicle (n=8) were stereotactically transplanted into the left striatum. Using rotarod test, motor function was serially evaluated through the experiment. A 7.0-T MR apparatus was employed to serially monitor the migration of BMSCs in the host brain. Histological analysis was performed at 7 weeks after ouabain injection, i.e., 6 weeks after BMSC transplantation. Ouabain injection yielded the reproducible, focal lesion in the right striatum, causing continuous motor dysfunction throughout the experiment. BMSC transplantation significantly enhanced the recovery of motor function after ouabain injection. MR imaging demonstrated that the BMSCs aggressively migrated towards the lesion through the corpus callosum. Histological analysis supported the findings on MRI. The BMSCs significantly enhanced the neurogenesis in the subventricular zone (SVZ) on both sides. Some of them also expressed neuronal or astrocytic phenotypes in the neocortex, SVZ, corpus callosum, and pen-lesion area. These findings strongly suggest that the BMSCs may serve therapeutic impacts on lacunar stroke when stereotactically transplanted at clinically relevant timing.