Morton A J, Williams M N, Emson P C, Faull R L
MRC Molecular Neuroscience Group, Babraham Institute, Cambridge, UK.
J Neurocytol. 1995 Aug;24(8):568-84. doi: 10.1007/BF01257373.
Cells from a human neuroblastoma cell line (SH-SY5Y) have been used to examine their potential suitability as donor cells for neural transplantation. Grafts of SH-SY5Y cells were placed in the basal ganglia of the rat brain 7 days after kainic acid lesions of the striatum. The animals were killed 4 or 8 weeks following grafting, and light and electron microscopic studies showed that the graft formed a well-vascularized compact mass of cells in the host brain. At both time points grafted cells showed evidence of cellular differentiation with process formation, especially at the graft-host interface where there was intermingling of graft and host neuronal process. Electron microscopic studies showed that graft cell processes containing irregularly-shaped, clear vesicles or membrane-bound dense core vesicles, established regions of specialized contact with other graft cells and formed close associations with host neuronal processes. There was little difference between the grafts of different ages, except that in the older grafts there were early signs of neurodegeneration. Since the SH-SY5Y cells used in these grafts express the enzyme tyrosine hydroxylase and synthesize dopamine in vitro, these cells were used in the hope that they may potentially be useful for repairing lesions in the dopamine pathway, such as that seen in Parkinson's disease. Our behavioural studies show that grafting SH-SY5Y cells into the striatum of rats with 6-hydroxydopamine lesions of the median forebrain bundle result in a reduction of amphetamine-induced rotation. However, this was unlikely to be due to dopamine release since there was no tyrosine hydroxylase immunoreactivity seen in the region of the grafts. Thus grafted human neuroblastoma cells survive, establish specialized morphological associations with graft and host processes and improve behavioural deficits resulting from 6-hydroxydopamine lesions. We suggest that grafted differentiated human neuroblastoma cells can interact with cells in the host brain with beneficial effects, and that in the medium-term, neuroblastoma grafts will make useful models for examining graft-host interactions. However, the presence of early degenerative changes in the older grafts suggests that neuroblastoma cells may not be suitable for long-term neural transplantation therapy for neurodegenerative diseases.
人类神经母细胞瘤细胞系（SH - SY5Y）的细胞已被用于检测其作为神经移植供体细胞的潜在适用性。在纹状体经 kainic 酸损伤 7 天后，将 SH - SY5Y 细胞移植到大鼠脑的基底神经节。移植后 4 周或 8 周处死动物，光镜和电镜研究显示，移植组织在宿主脑内形成了一个血管化良好的紧密细胞团。在两个时间点，移植细胞均显示出有细胞分化及突起形成的迹象，尤其是在移植 - 宿主界面处，移植细胞与宿主神经元突起相互交织。电镜研究表明，移植细胞的突起含有形状不规则的清亮小泡或膜结合的致密核心小泡，与其他移植细胞建立了特殊接触区域，并与宿主神经元突起形成紧密联系。不同年龄的移植组织之间差异不大，只是在较老的移植组织中有神经退行性变的早期迹象。由于这些移植中使用的 SH - SY5Y 细胞在体外表达酪氨酸羟化酶并合成多巴胺，使用这些细胞是希望它们可能对修复多巴胺通路损伤（如帕金森病中所见）有用。我们的行为学研究表明，将 SH - SY5Y 细胞移植到经 6 - 羟基多巴胺损伤中脑前脑束的大鼠纹状体中，可减少苯丙胺诱导的旋转。然而，这不太可能是由于多巴胺释放，因为在移植区域未见酪氨酸羟化酶免疫反应性。因此，移植的人类神经母细胞瘤细胞能够存活，与移植组织和宿主突起建立特殊的形态学联系，并改善 6 - 羟基多巴胺损伤导致的行为缺陷。我们认为，移植的分化人类神经母细胞瘤细胞可与宿主脑中的细胞相互作用并产生有益效果，并且从中期来看，神经母细胞瘤移植将成为研究移植 - 宿主相互作用的有用模型。然而，较老移植组织中存在早期退行性变化表明，神经母细胞瘤细胞可能不适用于神经退行性疾病的长期神经移植治疗。
