Chen X L, Roisen F J, Gupta M
Department of Anatomical Sciences & Neurobiology, University of Louisville School of Medicine, Kentucky 40292, USA.
Exp Neurol. 1996 Mar;138(1):64-72. doi: 10.1006/exnr.1996.0047.
The ability of PC12 cells to regenerate processes is substantially enhanced in vitro if 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.
与未接触过神经生长因子（NGF未预处理）的细胞相比，如果PC12细胞之前接触过神经生长因子（NGF预处理），其在体外再生突起的能力会显著增强。进行这些研究是为了确定NGF预处理细胞增强的神经突生成能力在移植后是否得以保留。将NGF未预处理或NGF预处理的PC12细胞移植到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素A（CyA）以防止异种移植物排斥。通过酪氨酸羟化酶免疫反应性观察移植的PC12细胞。超过一半的动物中，NGF未预处理的移植细胞形成了密集的簇和大的肿瘤块。只有少数未预处理的PC12细胞有短突起。相比之下，许多移植的NGF预处理的PC12细胞有突起。此外，与接受NGF未预处理细胞的动物相比，移植预处理细胞的动物纹状体中产生肿瘤块的较少。与MPTP处理的动物相比，移植NGF未预处理的PC12细胞会导致宿主黑质（SN）中多巴胺能神经元数量显著增加。使用NGF预处理的PC12细胞时，宿主多巴胺能神经元的增加没有统计学意义。在MPTP处理和PC12细胞移植后，注射CyA对宿主SN中的多巴胺能神经元没有影响。这些数据表明，移植前细胞接触营养因子可增强其分化水平并促进其整合到宿主脑中。
