Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats.
Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats.
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DOI：
10.1016/j.brainres.2008.07.116
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发表时间：
2008-10-21
期刊：
影响因子：
2.9
通讯作者：
Kocsis JD
中科院分区：
文献类型：
--
作者：
Omori Y;Honmou O;Harada K;Suzuki J;Houkin K;Kocsis JD
从成年骨髓制备的人骨髓间充质干细胞(HMSCs)全身注射对大鼠脑动脉闭塞后具有治疗作用，并且由于细胞对特定的病理微环境有反应，可能在病变内的不同部位和不同时间具有多种治疗效果。然而，在大鼠脑动脉闭塞后不同时间点多次注射hMSCs的疗效比较尚不清楚。本研究采用血管腔内结扎法建立大鼠大脑中动脉闭塞(MCAO)模型，在MCAO后6h的单个时间点(低细胞剂量和高细胞剂量)和不同的多个时间点静脉注射hMSCs。根据MRI分析，与单独注射血清相比，所有hMSC注射组的病变体积都减小了。然而，在MCAO后6h单次大剂量细胞注射的治疗效果最好，而不是在多个时间点多次低剂量细胞输注。病变内毛细血管的三维分析表明，所有细胞注射组的毛细血管体积都有相同程度的增加。因此，hMSC移植亚组之间功能结果的差异不太可能是血管生成的差异，而是神经保护效果的差异。
The systemic injection of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has therapeutic benefits after cerebral artery occlusion in rats, and may have multiple therapeutic effects at various sites and times within the lesion as the cells respond to a particular pathological microenvironment. However, the comparative therapeutic benefits of multiple injections of hMSCs at different time points after cerebral artery occlusion in rats remain unclear. In this study, we induced middle cerebral artery occlusion (MCAO) in rats using intra-luminal vascular occlusion, and infused hMSCs intravenously at a single 6 h time point (low and high cell doses) and various multiple time points after MCAO. From MRI analyses lesion volume was reduced in all hMSC cell injection groups as compared to serum alone injections. However, the greatest therapeutic benefit was achieved following a single high cell dose injection at 6 h post-MCAO, rather than multiple lower cell infusions over multiple time points. Three-dimensional analysis of capillary vessels in the lesion indicatedthat the capillary volume was equally increased in all of the cell-injected groups. Thus, differences in functional outcome in the hMSC transplantation subgroups are not likely the result of differences in angiogenesis, but rather from differences in neuroprotective effects.
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