Intra-arterial infusion of human bone marrow-derived mesenchymal stem cells results in transient localization in the brain after cerebral ischemia in rats
Intra-arterial infusion of human bone marrow-derived mesenchymal stem cells results in transient localization in the brain after cerebral ischemia in rats
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DOI：
10.1016/j.expneurol.2012.09.018
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发表时间：
2013-01-01
影响因子：
5.3
通讯作者：
Jolkkonen, Jukka
中科院分区：
文献类型：
--
作者：
Mitkari, Bhimashankar;Kerkela, Erja;Jolkkonen, Jukka
各种来源的细胞疗法一直在中风中进行深入研究。细胞有效地归巢到受伤的大脑而没有并发症是实现细胞疗法的治疗潜力所必需的。动脉内（IA）细胞输注绕过过滤器官，并更有效地将细胞引导至靶区域。在这里，我们研究了人骨髓间充质干细胞（BMMSCs）直接注入大鼠颈外动脉（ECA）后的生物分布。细胞，这是培养没有动物源性的代理商，也与蛋白水解酶瞬时修改细胞表面粘附蛋白，注入短暂的大脑中动脉闭塞（MCAO）后24小时。SPECT成像后立即细胞输注和24小时后，跟踪在111-oxine标记的BMMSC在假手术和MCAO大鼠。在大鼠中IA输注BMMSCs导致细胞立即滞留在脑中，但大部分信号在接下来的24小时内消失并重新定位到内脏。在MCAO大鼠中，输注后24小时，缺血半球的放射性计数高于对侧半球。我们的研究结果表明，IA输注通过ECA是一种安全和有效的管理途径，BMMSCs在大鼠脑中的细胞在一个短暂的定位。(c)2012 Elsevier Inc. All rights reserved.
Cell therapies from various sources have been under intense research in stroke. Efficient homing of the cells to the injured brain without complications is necessary to realize the therapeutic potential of cell therapy. Intra-arterial (IA) infusion of cells bypasses the filtering organs and directs the cells to the target area more efficiently. Here we studied the biodistribution of human bone marrow-derived mesenchymal stromal/stem cells (BMMSCs) after a direct infusion into the external carotid artery (ECA) in rats. Cells, which were cultured without animal-derived agents and also treated with a proteolytic enzyme to transiently modify cell surface adhesion proteins, were infused 24 h after transient middle cerebral artery occlusion (MCAO). SPECT imaging was used immediately after cell infusion and 24 h thereafter to track In-111-oxine-labeled BMMSC in sham-operated and MCAO rats. IA infusion of BMMSCs in rats resulted in immediate cell entrapment in the brain, but the majority of the signal disappeared during the next 24 h and relocated to the internal organs. In MCAO rats, radioactivity counts 24 h after infusion were higher in the ischemic hemisphere compared to the contralateral hemisphere. Our results showed that IA infusion through ECA is a safe and efficient administration route for BMMSCs resulting in a transient localization of cells in the rat brain. (c) 2012 Elsevier Inc. All rights reserved.