Transplantation Of Neural Stem Cells In The Hippocampus Of Vascular Dementia Rats

Objective Neural stem cells isolated from spinal cord of neonatal rats were transplanted into the hippocampus of adult vascular dementia rats to study their survival,migration and differentiation.Methods Cells which had ability to form clones were isolated from spinal cord of neonatal rats by using serum-free cell culture and single cell clone test.Clones were passaged continuously in order to acquire a large number of clones, and immuno-fluorescence was used to detect Nestin antigan of the clone and specific antigen of mature neural cell after the clone differentiated.The vascular dementia model was reproduced by permanent occlusion of bilateral common carotid arteries of rats.Abilities of learning and memory of rats were tested by using the Morris water maze. Meanwhile,the histomorphology of hippocampus was observed and analyzed by microcopy.Cells which were cultured before were labeled and transplanted into hippocampus of adult vascular dementia rats. Immunofluorescence was used to detect survival, migration and differentiation of BrdU-labeled cells.Results Cells isolated from spinal cord of neonatal rats express Nestin antigen and have the potential to form clones and differentiate into neurons,gliacytes.The average eacape latency of model rat was longer than that in control in place navigation test From spatial probe test, it was seen that the lingering time of model rat in platform area was shorter than that of control. Loss of cells was seen in CA1 subfield of hippocampus 37 days after occlusion of bilateral common carotid arteries on rats. Neural stem cells which were transplanted into hippocampus of vascular dementia rats eight weeks before can be detected,which indicates they can survive,migrate and differentiate. Tranplanted cells that integrated in the granular cell layer and CA1subfield differentiated into cells characteristic of these region,whereas engraftment into other hippocampal regions result in the differentiation of cells with astroglial and oligodendroglial phenotypes.Conclusion Cells which express Nestin antigen are multipotent cells and have ability to self-renew,and believed that they contain stem cells of spinal cord.The kind of model reproduced by permanent occlusion of bilateral common carotid arteries of rats resulted in dementia.When transplanted these cells into the hippocampus of vascular dementia rats, the data indicate that clonally expanded,multipotent stem cells from a non-neurogenic region are not lineage-restricted to their developmental origin but can generate region-specific neurons and glias in vivo when exposed to the appropriate environmental cues.