Becerra G D, Tatko L M, Pak E S, Murashov A K, Hoane M R
Restorative Neuroscience Laboratory, Center for Integrative Research in Cognitive and Neural Sciences, Department of Psychology, Southern Illinois University, Carbondale, IL 62901, USA.
Behav Brain Res. 2007 Apr 16;179(1):118-25. doi: 10.1016/j.bbr.2007.01.024. Epub 2007 Feb 1.
Embryonic stem (ES) cells have been investigated in many animal models of injury and disease. However, few studies have examined the ability of pre-differentiated ES cells to improve functional outcome following traumatic brain injury (TBI). The purpose of the present study was to compare the effect of murine ES cells that were pre-differentiated into GABAergic neurons or astrocytes on functional recovery following TBI. Neural and astrocyte induction was achieved by co-culturing ES cells on a bone marrow stromal fibroblast (M2-10B4) feeder layer and incubating them with various mitogenic factors. Rats were initially prepared with a unilateral controlled cortical contusion injury of the sensorimotor cortex or sham procedure. Rats were transplanted 7 days following injury with approximately 100K GABAergic neurons, astrocytes, fibroblasts, or media. Animals were assessed on a battery of sensorimotor tasks following transplantation. The stromal fibroblast cells (M2-10B4), as a control cell line, did not differ significantly from media infusions. Transplantation of GABAergic neurons facilitated complete and total recovery on the vibrissae-forelimb placing test as opposed to all other groups, which failed to show any recovery. It was also found that GABAergic neurons reduced the magnitude of the initial impairment on the limb use test. Histological analysis revealed infiltration of host brain with transplanted neurons and astrocytes. The results of the present study suggest that transplantation of pre-differentiated GABAergic neurons significantly induces recovery of sensorimotor function; whereas, astrocytes do not.
胚胎干细胞（ES细胞）已在许多损伤和疾病的动物模型中得到研究。然而，很少有研究探讨预分化的ES细胞在创伤性脑损伤（TBI）后改善功能结局的能力。本研究的目的是比较预分化为γ-氨基丁酸能神经元或星形胶质细胞的小鼠ES细胞对TBI后功能恢复的影响。通过将ES细胞与骨髓基质成纤维细胞（M2-10B4）饲养层共培养并用各种促有丝分裂因子孵育来实现神经和星形胶质细胞的诱导。大鼠最初接受感觉运动皮层的单侧控制性皮质挫伤损伤或假手术。大鼠在受伤7天后移植约100K个γ-氨基丁酸能神经元、星形胶质细胞、成纤维细胞或培养基。移植后对动物进行一系列感觉运动任务评估。作为对照细胞系的基质成纤维细胞（M2-10B4）与培养基输注相比没有显著差异。与所有其他未能显示任何恢复的组相比，γ-氨基丁酸能神经元的移植促进了触须-前肢放置试验的完全和总体恢复。还发现γ-氨基丁酸能神经元降低了肢体使用试验中初始损伤的程度。组织学分析显示宿主脑内有移植的神经元和星形胶质细胞浸润。本研究结果表明，预分化的γ-氨基丁酸能神经元的移植显著诱导感觉运动功能的恢复；而星形胶质细胞则不能。
