Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats
Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats
复制标题
人骨髓间充质干细胞移植促进脑缺血大鼠行为恢复和内源性神经发生
DOI：
10.1016/j.brainres.2010.10.063
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发表时间：
2011-01-07
期刊：
影响因子：
2.9
通讯作者：
Wang, Renzhi
中科院分区：
文献类型：
--
作者：
Bao, Xinjie;Wei, Junji;Wang, Renzhi
间充质干细胞（MSCs）已成功用于治疗实验性中风。然而，MSC改善神经功能恢复的神经修复机制尚未完全了解。脑卒中后室管膜下区（SVZ）的内源性细胞增殖是众所周知的，但大多数新生细胞发生凋亡。在本研究中，我们测试的假设，即人骨髓来源的间充质干细胞（hBMSCs）分泌的神经营养因子促进内源性神经发生，减少凋亡，并改善功能恢复。成年大鼠大脑中动脉闭塞（MCAO）2小时，在缺血后3天将hBMSCs或生理盐水移植到同侧脑实质中。与对照动物相比，在MCAO后14天开始，hBMSCs治疗的大鼠的行为有显着恢复。与对照组相比，hBMSCs处理的大鼠脑中检测到更高水平的脑源性神经营养因子（BDNF）、神经营养素-3（NT-3）和血管内皮生长因子（VEGF）。人骨髓间充质干细胞治疗也增强了内源性细胞增殖在SVZ和海马的颗粒下区（SGZ）。此外，更多的神经元祖细胞从SVZ迁移到缺血边界区（IBZ），并分化为成熟的神经元，细胞凋亡较少。总的来说，这些数据表明，在促进内源性神经发生，保护新形成的细胞，并改善缺血后的功能恢复，在大鼠骨髓间充质干细胞的重要作用。(C)2010爱思唯尔有限公司版权所有。
Mesenchymal stem cells (MSCs) have been successfully used for the treatment of experimental stroke. However, the neurorestorative mechanisms by which MSCs improve neurological functional recovery are not fully understood. Endogenous cell proliferation in the subventricular zone (SVZ) after stroke is well known, but most of newly formed cells underwent apoptosis. In the present study, we tested the hypothesis that neurotrophic factors secreted by human bone marrow-derived MSCs (hBMSCs) promote endogenous neurogenesis, reduce apoptosis, and improve functional recovery. Adult rats subjected to 2-h middle cerebral artery occlusion (MCAO) were transplanted with hBMSCs or saline into the ipsilateral brain parenchyma at 3 days after ischemia. There was a significant recovery of behavior in the hBMSCs-treated rats beginning at 14 days after MCAO compared with the control animals. Higher levels of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and vascular endothelial growth factor (VEGF) were detected in the hBMSCs-treated rat brain than the control. Human BMSCs treatment also enhanced endogenous cell proliferation both in the SVZ and in the subgranular zone (SGZ) of the hippocampus. In addition, more neuronal progenitor cells migrated from the SVZ to the ischemic boundary zone (IBZ) and differentiated into mature neurons with less apoptosis in rats treated with hBMSCs. Overall, these data suggest an essential role for hBMSCs in promoting endogenous neurogenesis, protecting newly formed cells, and improving functional recovery after ischemia in rats. (C) 2010 Elsevier B.V. All rights reserved.