The effect of prior in vitro exposure of donor cells to trophic factors in neurotransplantation.

The effect of prior in vitro exposure of donor cells to trophic factors in neurotransplantation.
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神经移植中供体细胞先前体外暴露于营养因子的影响。

DOI:
10.1006/exnr.1996.0047
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发表时间:
1996
期刊:
Experimental neurology.
影响因子:
--
通讯作者:
Gupta,M
Gupta,M
中科院分区:
--
文献类型:
--
作者:
Chen,XL;Roisen,FJ;Gupta,M

文献摘要

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与未接触过神经生长因子(NGF-naive)的细胞相比,如果之前接触过神经生长因子(NGF-primed),PC12细胞再生过程的能力在体外显着增强。进行这些研究是为了确定 NGF 引发的细胞在移植后是否保留增强的神经突形成能力。将未经 NGF 或 NGF 引发的 PC12 细胞移植到经 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 处理的小鼠纹状体中,并使其存活 2 周。每天给小鼠注射环孢菌素 A (CyA),以防止抗物种移植排斥。通过酪氨酸羟化酶免疫反应性观察移植的 PC12 细胞。未经 NGF 移植的细胞在一半以上的动物体内形成了密集的簇和大的肿瘤块。只有少数初始 PC12 细胞具有短突起。相比之下,许多移植的 NGF 引发的 PC12 细胞都有突起。此外,与接受 NGF 初始细胞的动物相比,移植初免细胞的动物在纹状体中产生肿瘤块的数量较少。与 MPTP 处理的动物相比,移植未经 NGF 的 PC12 细胞会导致宿主黑质 (SN) 中多巴胺能神经元的数量显着增加。当使用 NGF 引发的 PC12 细胞时,宿主多巴胺能神经元的增加没有统计学意义。 MPTP 治疗和 PC12 细胞移植后,注射 CyA 不会影响宿主 SN 中的多巴胺能神经元。这些数据表明,在移植之前将细胞暴露于营养因子可以提高它们的分化水平和融入宿主大脑的水平。
The ability of PC12 cells to regenerate processes is substantially enhancedin vitroif they have been previously exposed to nerve growth factor (NGF-primed), compared to cells that have not been exposed (NGF-naive). These studies were carried out to determine if the enhanced neuritogenic ability of NGF-primed cells is retained following transplantation. NGF-naive or NGF-primed PC12 cells were transplanted into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and allowed to survive for 2 weeks. Mice were given daily injections of cyclosporin A (CyA) to prevent anti-species graft rejection. The transplanted PC12 cells were visualized by tyrosine hydroxylase immunoreactivity. The NGF-naive transplanted cells formed dense clusters and large tumor masses in more than half the animals. Only a few of the naive PC12 cells had short processes. In contrast, many of the transplanted NGF-primed PC12 cells had processes. Furthermore, fewer of the animals transplanted with primed cells produced tumor masses in the striatum compared to animals that received NGF-naive cells. Transplantation of NGF-naive PC12 cells leads to a significant increase in the number of dopaminergic neurons in the host substantia nigra (SN) compared to MPTP-treated animals. The increase of host dopaminergic neurons was not statistically significant when NGF-primed PC12 cells were used. Following MPTP treatment and PC12 cell transplantation, injection of CyA did not affect the dopaminergic neurons in the host SN. These data suggest that exposure of cells to trophic factors, prior to transplantation, can enhance their level of differentiation and integration into the host brain.