MORPHOLOGICAL AND BIOCHEMICAL STUDY IN BRAIN TRANSPLANTATION OF NEURAL TISSUE

神经组织脑移植的形态学和生化研究

• 批准号: 07671539
• 负责人: OKUDA Osamu
• 金额: $ 1.34万
• 依托单位: JUNTENDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671539/
• 关键词: BRAIN TRANSPLANTATION; NEUROTRANSMITTER DEFICIENCY SYNDROME; PC 12 CELL; ONCOGENE; RAT

Neuronal cells establishing from cell lines can offer a well-characterized source of cells for transplantation to the brain that is an alternative to fetal neurons. The infection of the PC 12 cell line with a retrovirus containing ras-oncogene leads to their neuronal differentiation without the need of nerve growth factor (NGF). We find that neoplastic, naive PC12 cells grafted to the striatum of normal adult rats cause the transient formation of large hemorrhagic cavities and do not survive. After differentiation by infection with Kirsten-ras murine sarcoma virus, and transplantation to the opposite striatum of the same brain, PC12 cells survive for at least 8 weeks and emit neurites. These neuron-like cells and their neurites retain tyrosine hydroxylase and choline acetyl transferase, as detected immunohistochemically. Thus, ras-primed PC12 cells may serve as a continuous source for both cholinergic and dopaminergic transmitters, in vivo, without the need of exogenous NGF.In addition to the PC 12 cell lines, we also find that rat amniotic epithelial cells can be differentiated to neuronal cells, thus these cells also may be useful for neuronal transplantation as a non-neoplastic candidate.

从细胞系建立的神经元细胞可以提供用于移植到脑的细胞的良好表征的来源，其是胎儿神经元的替代物。用含有ras癌基因的逆转录病毒感染PC 12细胞系，导致其神经元分化，而不需要神经生长因子（NGF）。我们发现，肿瘤，幼稚的PC 12细胞移植到正常成年大鼠的纹状体引起大出血腔的短暂形成，不能存活。在通过用Kirsten-ras鼠肉瘤病毒感染分化并移植到同一脑的对侧纹状体后，PC 12细胞存活至少8周并发出神经突。这些神经元样细胞和它们的神经突保留酪氨酸羟化酶和胆碱乙酰转移酶，如电化学检测。因此，ras致敏的PC 12细胞可以作为胆碱能和多巴胺能递质的连续来源，在体内，而不需要外源性NGF.In除了PC 12细胞系，我们还发现，大鼠羊膜上皮细胞可以分化为神经元细胞，因此这些细胞也可能是有用的神经元移植作为一个非肿瘤的候选人。