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Grafted stem cells may confer benefi cial effects to the recipient brain in a twofold manner: (1) they produce a cocktail of trophic factors and thus promote endogenous repair mechanisms and also act neuroprotective for endangered neurons and (2) they differentiate into neurons and glial cells and replace dead cells. We have transplanted pre-differentiated mouse EGFP+ embryonic stem cells 7 days after experimental stroke into rats. After 4 weeks cells had been differentiated into neurons and astrocytes. We detected several sub-types of neurons by means of neurotransmitter expression and electric activity. However, cells displayed limited migratory activity and cell survival declined substantially after 12 weeks. Bone marrow stromal cells (MSC) have been described to be neuroprotective. We found that MSC are neuroprotective to organotypic hippocampal slice cultures subjected to an oxygen-glucose deprivation (OGD) even without having direct cell–cell contact. This effect was increased if MSC were treated by complete serum deprivation before delivery to OGD treated slices. Interestingly, OGD damaged slices stimulated the MSC to produce certain growth factors like bFGF and NGF. A complete serum-deprivation induces the generation of a subpopulation of small-sized cells expressing nestin, GFAP, Sox-2 and Oct4 and by this resembling both neural and embryonic stem stem cells. It remains open whether this sub-population has the potential to differentiate into neuroectodermal cells.
Transplantation of stem cells is currently investigated as an option for treatment of stroke. In this study we transplanted adult human cells NNC1 derived from brain biopsy after experimental stroke in rats. Transient ischemia in rats was performed by the fi lament model of middle cerebral artery occlusion (fMCAO). About 3×105 NNC1 cells were transplanted near to the necrotic area 7 days after fMCAO and the brain of treated rats was investigated 4 weeks after transplantation. Rats were immunosuppressed by daily injections of cyclosporine A, prednisolone and azathioprine. Grafted cells were localized by anti-human specifi c antibodies HuNu and MTC02. Cells appeared to be located dispersed, however there was almost no cell-migration. The number of localized NNC1 cells 4 weeks after transplantation was rather limited indicating a reduced survival rate which was probably caused by host versus graft rejection processes. The latter is refl ected by activation of Ox42 and ED1 positive microglia/macrophages. Also, we detected CD8 and TCR positive T-cells infi ltrating to the necrotic area. Immunocytochemical analysis revealed expression of nestin and βIII-tubulin by grafted NNC1. Interestingly, some βIII tubulin expressing NNC1 were found to be located in blood vessels. In conclusion, both the survival and the capacity to neuronal differentiation of grafted NNC1 cells are limited.
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