Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury
Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury
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DOI：
10.1016/j.brainres.2004.07.087
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发表时间：
2004-11-05
期刊：
影响因子：
2.9
通讯作者：
Stein, DG
中科院分区：
文献类型：
--
作者：
Shear, DA;Tate, MC;Stein, DG
研究表明，神经祖细胞（NPC）的多功能性最近重新点燃了兴趣，旨在治疗创伤性脑损伤（TBI）的神经移植方法。然而，很少有研究评估移植NPC的安全性和功能性疗效超过几个月。本研究的目的是评估移植到TBI小鼠模型中的NPC在移植后1年的长期存活、迁移、分化和功能意义。NPC来源于含有转基因表达绿色荧光蛋白（GFP）的E14.5小鼠脑，并在含有FGF 2的培养基中培养为神经球。在单侧皮质撞击损伤后1周，将神经球注射到成年C57 BL/6小鼠的同侧纹状体中。行为测试显示，早在第一周，NPC治疗小鼠的运动能力就有了显著改善，并且恢复持续到移植后一年。此外，接受NPC移植的小鼠在3个月和1年时显示出空间学习能力的显着改善，而在1个月时检测到对该行为参数的中间治疗效果。在移植后14个月，GFP（+）NPC在整个受损的海马和移植大脑的邻近皮质区域观察到。免疫组织化学分析显示，大多数移植细胞共标记NG 2，少突胶质细胞祖细胞标记，但不标记神经元，星形胶质细胞或小胶质细胞标记。总之，移植的NPC在宿主脑中存活长达14个月，迁移到损伤部位，增强运动和认知恢复，并可能在TBI后的营养支持中发挥作用。(C)2004 Elsevier B. V.保留所有权利。
Studies demonstrating the versatility of neural progenitor cells (NPCs) have recently rekindled interest in neurotransplantation methods aimed at treating traumatic brain injury (TBI). However, few studies have evaluated the safety and functional efficacy of transplanted NPCs beyond a few months. The purpose of this study was to assess the long-term survival, migration, differentiation and functional significance of NPCs transplanted into a mouse model of TBI out to 1 year post-transplant. NPCs were derived from E14.5 mouse brains containing a transgene-expressing green fluorescent protein (GFP) and cultured as neurospheres in FGF2-containing medium. Neurospheres were injected into the ipsilateral striatum of adult C57BL/6 mice I week following unilateral cortical impact injury. Behavioral testing revealed significant improvements in motor abilities in NPC-treated mice as early as I week, and the recovery was sustained out to I year post-transplant. In addition, mice receiving NPC transplants showed significant improvement in spatial learning abilities at 3 months and 1 year, whereas an intermediate treatment effect on this behavioral parameter was detected at 1 month. At 14 months post-transplant, GFP(+) NPCs were observed throughout the injured hippocampus and adjacent cortical regions of transplanted brains. Immumohistochemical analysis revealed that the majority of transplanted cells co-labeled for NG2, an oligodendrocyte progenitor cell marker, but not for neuronal, astrocytic or microglial markers. In conclusion, transplanted NPCs survive in the host brain up to 14 months, migrate to the site of injury, enhance motor and cognitive recovery, and may play a role in trophic support following TBI. (C) 2004 Elsevier B.V. All rights reserved.