Survival and neuronal differentiation of transplanted stem cells derived from embryonic hippocampus in adult rats with stroke lesions

AIM: To study whether exogenous neural stem cells (NSCs) derived from embryonic hippocampus differentiates into the neurons after transplanted into the infarct periphery of the brain in a stroke model and to further investigate the behavioral improvement in the rats.METHODS: The NSCs were prepared after isolated from the embryonic hippocampus of green fluorescent protein (GFP)-transgenic rats and cultured. The NSCs were identified using nestin and doublecortin(DCX) as markers. The cortical infarction in rats was induced using photochemical method, named photothrombotic cortical injury (PCI). Twenty adult rats were randomly divided into NSC transplantation group (NSC group) and control group. The cultured NSCs were transplanted into the infarct periphery of the rats in NSC group, and nothing in control group at first day was applied after PCI. The locomotor behavior of animals was checked using the rotarod test at 1st, 7th, 14th and 21st d after PCI. The survival and differentiation of transplanted NSCs were evaluated by immunocytochemical method at 12th week after PCI.RESULTS: The cells derived from the embryonic hippocampus significantly expressed the markers of NSCs. The grafted cells survived at least 12 weeks in the infarct periphery of adult rats and differentiated into mature glial cells and neurons. The density of NeuN+/GFP+ and volume of grafts at 12th week were less than those at 3rd week after transplantation (P<0.05). The time standing on the rod was longer in NSC group than that in control group at 7th, 14th and 21st d after PCI (P<0.01).CONCLUSION: The NSCs derived from embryonic hippocampus survive in the infarct periphery of adult rats up to 12 weeks and differentiate into mature neurons, which might be associated with the improvement of locomotor behavior of stroke animals. The neuronal replacement of neurons differentiated from NSCs may be the underlying mechanism.