, Volume 24, Issue 8, pp 568-584

The morphology of human neuroblastoma cell grafts in the kainic acid-lesioned basal ganglia of the rat

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Summary

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 irregularlyshaped, 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 dopaminein 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.