Engraftment of human mesenchymal stem cells in a rat photothrombotic cerebral infarction model : comparison of intra-arterial and intravenous infusion using MRI and histological analysis.

Engraftment of human mesenchymal stem cells in a rat photothrombotic cerebral infarction model : comparison of intra-arterial and intravenous infusion using MRI and histological analysis.
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DOI:
10.3340/jkns.2013.54.6.467
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发表时间:
2013-12
影响因子:
1.6
通讯作者:
Park S
Park S
中科院分区:
医学4区
文献类型:
--
作者:
Byun JS;Kwak BK;Kim JK;Jung J;Ha BC;Park S

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本研究旨在评估给药途径[动脉内(IA)vs.静脉内(IV)]影响急性脑梗死患者移植的人骨髓间充质干细胞(hBM-MSCs)早期迁移的假设。对雄性Sprague-Dawley大鼠(n=40)进行光血栓性梗死。在光致血栓形成梗死后3天,将大鼠随机分配到四个实验组之一[IA组:n=12,IV组:n=12,超顺磁性氧化铁(SPIO)组:n=8,对照组:n=8]。根据处死时间点,将所有组再分为1、6、24和48小时组。在植入前和植入后1、6、24和48 h获得大鼠脑的磁共振成像(MRI),包括T2加权像(T2 WI)、T2* 加权像(T2*WI)、磁敏感加权像(SWI)和弥散加权像。最后一次MRI后,处死大鼠,并使用普鲁士蓝和免疫组织化学染色分析脑和肺标本中的移植细胞。移植的细胞在病变周围区表现为暗信号强度区域。IA组病灶周围暗信号较IV组明显。IA组和IV组的SWI显示最大暗信号,其次是T2*WI和T2 WI。在普鲁士蓝染色上,IA给药显示出比IV给药显著增加的迁移和靶脑中大量的移植hBM-MSC。SPIO组和对照组未见普鲁士蓝阳性细胞。在缺血性中风的大鼠光血栓形成模型中,选择性IA施用人间充质干细胞比IV施用更有效。MRI和组织学分析揭示了细胞迁移的时间过程,以及hBM-MSCs递送到脑中的数量和分布。
This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction. Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), T2* weighted image (T2*WI), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining. Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by T2*WI and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups. In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.
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