Embryonic and adult stem cells for treatment of stroke
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.