One-year follow-up after bone marrow stromal cell treatment in middle-aged female rats with stroke
One-year follow-up after bone marrow stromal cell treatment in middle-aged female rats with stroke
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DOI：
10.1161/strokeaha.106.481218
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发表时间：
2007-07-01
期刊：
影响因子：
8.3
通讯作者：
Chopp, Michael
中科院分区：
文献类型：
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作者：
Shen, Li Hong;Li, Yi;Chopp, Michael
背景和目的 - 我们试图评估骨髓基质细胞 (BMSC) 治疗对患有中风的退休饲养大鼠的长期影响。方法 - 对雌性退休饲养大鼠进行 2 小时大脑中动脉闭塞 (MCAO)，然后在中风后 1 天将 2 X 10(6) 雄性 BMSC (n=8) 或磷酸盐缓冲盐水 (n=11) 注射到同侧颈内动脉中。一年后，这些老鼠被人道处死。进行了功能测试、原位杂交、组织化学和免疫组织化学染色。结果-与对照动物相比，在细胞注射后两周开始，BMSC 治疗的大鼠的神经功能缺陷显着恢复。细胞移植的有益效果持续至少一年（P < 0.01）。 Y染色体原位杂交显示，供体细胞在受体大鼠脑中存活，其中22.3±1.95%的细胞表达星形胶质细胞标记物胶质纤维酸性蛋白，16.8±2.13%表达神经元标记物微管相关蛋白2，5.5±0.42%和<1%的细胞与小胶质细胞标记物IB4和小胶质细胞共定位。内皮细胞标志物冯维勒布兰德因子。然而，在受体大鼠的心、肺、肝、脾、肾等外周器官中仅发现极少量的骨髓间充质干细胞。 BMSC 显着减少轴突丢失（P < 0.01）、病灶疤痕壁厚度（P < 0.01）以及疤痕边缘 Nogo-A 阳性细胞数量（P < 0.05）；同时，与未治疗的对照大脑相比，经BMSC治疗的缺血脑中突触素表达显着增加（P < 0.05）。 结论 - BMSC对缺血脑组织的有益作用持续至少1年。大多数存活的骨髓间充质干细胞存在于缺血的大脑中，但在其他器官中发现的很少。功能结果的长期改善可能与 BMSC 诱导的结构和分子变化有关。
Background and Purpose - We sought to evaluate the long-term effects of bone marrow stromal cell (BMSC) treatment on retired breeder rats with stroke.Methods - Female retired breeder rats were subjected to 2-hour middle cerebral artery occlusion (MCAO) followed by an injection of 2 X 10(6) male BMSCs (n=8) or phosphate-buffered saline (n=11) into the ipsilateral internal carotid artery at 1 day after stroke. The rats were humanely killed 1 year later. Functional tests, in situ hybridization, and histochemical and immunohistochemical staining were performed.Results - Significant recovery of neurological deficits was found in BMSC-treated rats beginning 2 weeks after cell injection compared with control animals. The beneficial effects of cell transplantation persisted for at least 1 year (P < 0.01). In situ hybridization for the Y chromosome showed that donor cells survived in the brains of recipient rats, among which 22.3 +/- 1.95% of cells expressed the astrocyte marker glial fibrillary acidic protein, 16.8 +/- 2.13% expressed the neuronal marker microtubule-associated protein 2, and 5.5 +/- 0.42% and < 1% of cells colocalized with the microglial marker IB4 and the endothelial cell marker von Willebrand factor, respectively. Only very few BMSCs, however, were found in peripheral organs such as the heart, lung, liver, spleen, and kidney in recipient rats. BMSCs significantly reduced axonal loss (P < 0.01), the thickness of the lesion scar wall (P < 0.01), and the number of Nogo-A-positive cells (P < 0.05) along the scar border; meanwhile, synaptophysin expression (P < 0.05) was significantly increased in BMSC-treated ischemic brains compared with control untreated brains.Conclusions - The beneficial effects of BMSCs on ischemic brain tissue persisted for at least 1 year. Most surviving BMSCs were present in the ischemic brain, but very few were found in other organs. The long-term improvement in functional outcome may be related to the structural and molecular changes induced by BMSCs.