Neuroprotection by human neural progenitor cells after experimental contusion in rats
Neuroprotection by human neural progenitor cells after experimental contusion in rats
复制标题
DOI：
10.1016/j.neulet.2003.07.021
复制
发表时间：
2003-11-20
影响因子：
2.5
通讯作者：
Mathiesen, T
中科院分区：
文献类型：
--
作者：
Hagan, M;Wennersten, A;Mathiesen, T
神经前体/干细胞（HNPC）被认为是脑外伤后提供必需营养因子和促进变性神经元存活的细胞。由于这些原因，我们假设HNPC加入到损伤后区域可能会保护受损的神经元。实验性脑挫伤18只。损伤后立即向大鼠注射0.1 ml培养基（n = 8）。在病变的内侧边缘中的死细胞（n = 4）或活细胞（n = 6）。术后6天处死大鼠，并使用人核标记物（匈奴）、苏木精和Fluoro-Jade（FJ）通过免疫组织化学进行评价。在5/6只动物中，通过阳性匈奴染色可检测到人神经干细胞植入。未移植动物从进一步分析中排除。给予死亡HNPC或培养基的小鼠没有检测到匈奴免疫反应性。在接受媒介物和死细胞的大鼠之间进行FJ阳性变性内源性神经元的数量之间的统计学比较，以评价与单独的媒介物相比，人细胞的存在是否会增加神经元变性。接受媒介物的大鼠具有117.5个FJ阳性细胞的中值，并且每个计数的切片具有175.0个死亡的祖细胞受体（P < 0.05，Mann-Whitney）。因此，选择接受死亡人细胞的动物作为接受活祖细胞的动物的对照。与对照组相比，接受活HNPC的大鼠每个计数切片显示出显著更少的FJ阳性细胞（58.0 vs. 175.0，P < 0.01，Mann-Whitney）。创伤后病灶周围环境允许活HNPC植入。逐步分析表明，宿主神经元变性是更高的动物移植非活的人神经元祖细胞比那些接受车辆，表明从引入外源抗原的旁观者效应。相反，移植活的祖细胞减弱神经元变性，表明祖细胞移植的潜在有益作用不仅限于移植细胞的恢复，而且还改善宿主细胞的存活。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
Neural progenitor/stem cells (HNPC) have been suggested to contribute essential trophic factors and promote survival of degenerating neurons after traumatic brain injury. For these reasons we hypothesize that the addition of HNPC to a post-injury region could possibly protect injured neurons. Experimental brain contusions were carried out in 18 rats. Immediately post-injury, rats were injected with 0.1 ml of medium (n = 8). dead cells (n = 4), or live cells (n = 6) in the medial border of the lesion. The rats were sacrificed 6 days post-surgery and evaluated by immunohistochemistry using a human nuclear marker (huN), hematoxylin and Fluoro-Jade (FJ). Human neural stem cells showed engraftment detectable by positive huN staining in 5/6 animals. The non-grafted animal was excluded from further analyses. Those given dead HNPC or medium showed no detectable huN immunoreactivity. A statistical comparison between the numbers of FJ positive degenerating endogenous neurons was made between rats receiving vehicle and dead cells to evaluate whether the presence of human cells would increase neuronal degeneration in comparison to vehicle alone. The rats receiving vehicle had a median of 117.5 FJ positive cells and dead progenitor cell recipients 175.0 per counted section (P < 0.05, Mann-Whitney). Consequently, the animals receiving dead human cells were chosen as controls to the animals receiving live progenitor cells. The rats that received live HNPC demonstrated significantly fewer FJ positive cells per counted section than controls (58.0 vs. 175.0, P < 0.01, Mann-Whitney). The post-traumatic perilesional environment allowed for the engraftment of live HNPC. The stepwise analysis indicated that host neuronal degeneration was higher in animals transplanted with non-viable human neuronal progenitor cells than in those receiving vehicle, indicating a bystander effect from introducing foreign antigen. In contrast, transplantation of viable progenitor cells attenuated neuronal degeneration, indicating that a potentially beneficial effect in progenitor cell transplantation is not limited to restoration by transplanted cells, but also improving survival of host cells. (C) 2003 Elsevier Ireland Ltd. All rights reserved.