Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia.
Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia.
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DOI：
10.1186/scrt79
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发表时间：
2011-09-22
影响因子：
7.5
通讯作者：
Jeun SS
中科院分区：
文献类型：
--
作者：
Lim JY;Jeong CH;Jun JA;Kim SM;Ryu CH;Hou Y;Oh W;Chang JW;Jeun SS
干细胞移植是治疗脑卒中的一种有前途的治疗策略。骨髓间充质干细胞（Mesenchymal stem cells，MSCs）是一种具有广泛应用前景的细胞来源。细胞治疗的安全性和有效性取决于细胞给药的方式。为探讨腰椎穿刺鞘内注射骨髓间充质干细胞（hUCB-MSCs）的治疗作用，我们将hUCB-MSCs鞘内或尾静脉注射到脑卒中大鼠模型的腰段脊髓内，观察hUCB-MSCs能否进入脑内、存活并促进脑卒中后神经功能恢复。在大脑中动脉闭塞诱导的中风后3天，给予hUCB-MSCs（1.0 × 106）。通过免疫组织化学方法检测hUCB-MSCs在大鼠脑组织中的存在及其存活和分化。在缺血后第7、14、21和28天，使用旋转杆试验和粘合剂去除试验检查施用hUCB-MSC后的运动协调性恢复。使用2-3-5-三苯基四唑（TTC）染色评价实验程序后7天的缺血性病变体积。与静脉内接受细胞的动物相比，通过LP鞘内接受hUCB-MSCs的大鼠在缺血区域内具有显著更高数量的迁移细胞。此外，鞘内给药的许多细胞存活，其中一部分表达成熟的神经谱系标志物，包括成熟神经元标志物NeuN和典型的星形胶质细胞胶质细胞酸性蛋白。与未治疗的对照动物相比，接受hUCB-MSCs的动物运动功能显著改善，缺血性损伤减少。无论给药途径如何，用1 × 106 hUCB-MSCs治疗的组显示出更好的神经恢复，两个治疗组之间没有显著差异。重要的是，鞘内注射5 × 105 hUCB-MSCs显著降低了缺血性损伤，但静脉注射组没有。此外，鞘内给药的细胞存活并更广泛地迁移到缺血区域，并显著分化为神经元和星形胶质细胞。总之，这些结果表明，通过LP鞘内施用MSC对于MSC治疗脑损伤（例如中风或神经退行性疾病）可能是有用的和可行的。
Stem cell transplantation is a promising therapeutic strategy for the treatment of stroke. Mesenchymal stem cells (MSCs) are a potential cell source for clinical application because they can be easily obtained and cultivated with a high proliferative capacity. The safety and efficacy of cell therapy depends on the mode of cell administration. To determine the therapeutic potential of intrathecal administration of MSCs by lumbar puncture (LP), we administrated human umbilical cord blood-derived MSCs (hUCB-MSCs) intrathecally into the lumbar spinal cord or intravenously into the tail vein in a rat model of stroke, and then investigated whether hUCB-MSCs could enter the brain, survive, and improve post-stroke neurological functional recovery. hUCB-MSCs (1.0 × 106) were administrated three days after stroke induced by occlusion of the middle cerebral artery. The presence of hUCB-MSCs and their survival and differentiation in the brain tissue of the rats was examined by immunohistochemistry. Recovery of coordination of movement after administration of hUCB-MSCs was examined using a Rotarod test and adhesive-removal test on the 7th, 14th, 21st, and 28th days after ischemia. The volume of ischemic lesions seven days after the experimental procedure was evaluated using 2-3-5-triphenyltetrazolium (TTC) staining. Rats receiving hUCB-MSCs intrathecally by LP had a significantly higher number of migrated cells within the ischemic area when compared with animals receiving cells intravenously. In addition, many of the cells administered intrathecally survived and a subset of them expressed mature neural-lineage markers, including the mature neuron marker NeuN and glial fibrillary acidic protein, typical of astrocytes. Animals that received hUCB-MSCs had significantly improved motor function and reduced ischemic damage when compared with untreated control animals. Regardless of the administration route, the group treated with 1 × 106 hUCB-MSCs showed better neurological recovery, without significant differences between the two treatment groups. Importantly, intrathecal administration of 5 × 105 hUCB-MSCs significantly reduced ischemic damage, but not in the intravenously treated group. Furthermore, the cells administered intrathecally survived and migrated into the ischemic area more extensively, and differentiated significantly into neurons and astrocytes. Together, these results indicate that intrathecal administration of MSCs by LP may be useful and feasible for MSCs treatment of brain injuries, such as stroke, or neurodegenerative disorders.
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影响因子：
3.7
作者：
Capone, Carmen;Frigerio, Simona;De Simoni, Maria-Grazia
通讯作者：
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