Intracerebral transplantation of bone marrow stromal cells in rats with cerebral ischemia:effects on neurofunctional recovery and histological investigation

Objective To observe the therapeutic effect of intraeerebral transplantation of bone marrow stromal ceils(BMSCs)on neurofunctionai recovery after cerebral infarction in rats,and investigate the survival and migration of the transplanted BMSCs in different areas of the ischemic lesion.Methods Seventy-five adult SD rats Were randomly divided into MCAO group(n=50)and BMSCs transplantation group(n=25).All the rats were subjected to middle cerebral artery occlusion(MCAO)by intraluminal filament placement for 1 h,and 24 h after MCAO,the rats in BMSCs transplantation group received iniection of 2x106 rat BMSCs into the ischemia hemisphere.Rotarod and modified adhesive removal tests were performed before and at 1,3,5,7,10and 14 days after MCAO.The rats were sacrificed after the last teSt to measure the sizes of the ischemic lesions and observe the survival and migration of the transplanted BMSCs using BrdU staining and immunohistochemical staining for glial fibrillary acidic protein(GFAP).Results In the rotarod test,significant neurological function recovery Was observed in rats receiving BMSC transplantation 7 days after MCAO in comparison with the rats withoutthe transplantation(P＜05).No obvious difference in the lesion sizes was found at 14 days after MCAO between the two groups.In rats receiving BMSCs transplantation,survival and migration of the transplanted BMSCs were identified in different areas of the ischemic lesion.BMSCs injected to the penumbra were found to survive better and preferentially migrate toward the lesion core.Only few BMSCs injected to the lesion core survived and no cell migration Was detected.Large amount of BrdU-positive cells were detected in the areas where activated GFAP-positive cells Were present.The migration of the BMSCs,however,appeared to be limited by the glial sear.Conclusions Intracerebral transplantation of BSMCs Can promote the moor function recovery of the rats after cerebral ischemia.The activated astrocytes provide appropriate environment for the survival of the transplanted BMSCs and allow their migration to the ischemic core,while the glial scar forms an obstacle to the migration of the BMSCs. Key words: Bone marrow stromal cells; Middle cerebral artery occlusion; Cerebral ischemia; Neurofunction