Abstract 2308: Timing Of Intra-arterial Cell Transplantation Drastically Affects The Behavior Of The Transplanted Cells And Functional Recovery After Stroke

Abstract

Background and Purpose- Intra-arterial delivery of human bone marrow stromal cells(hBMSCs)results in a migration of the greater number of cells compared to intra-venous delivery in an acute stage after stroke. However, it remains unclear how the timing of intra-arterial administration affects the cell migration, repair process and functional recovery. In this study, we test the hypothesis that the timing of intra-arterial cell transplantation changes the behavior of the transplanted cells and host environment, which is very important to achieve the optimal effect of transplantation. Methods- Sprague-Dawley rats (8week, 270∼300g) received 1X10 6 hBMSCs injected intra-arterially via polyethylene catheter at 1, 4 and 7 days (Day1,4 and 7 group) after 75 min middle cerebral artery occlusion following reperfusion. At the time point of transplantation, regional cerebral blood flow (rCBF) of ischemic core and periinfarct area was examined with transcranial laser Doppler flowmetry (LDF). Animals were sacrificed at 3 and 21 days after transplantation to assess the distribution of the cells, vascular density and final infarct volume with immunohistochemistry. Behavior assessment was also performed until 21 days after stroke. Results- In the periinfarct area of cerebral cortex, the number of hBMSCs was significantly greater in Day4 group than that in Day 1 group ( p =0.0001). On the other hand, there was no significant difference between Day1 and 4 groups in the periinfarct area of striatum. Fewer cells were found in both areas in Day 7 group. In Day1 group, the majority of hBMSCs migrated at ischemic core of cerebral cortex and striatum. rCBF of the ischemic core in cortex was the greatest in Day1 group. Otherwise, rCBF of the periinfarct area in cortex was the greatest in Day4 group. The number of hBMSCs was correlated with rCBF of each area. In Day1 and 4 groups, animals showed a significant increase in vascular density in the periinfarct area of cerebral cortex. However, a reduction of infarct volume and neurological recovery were seen in only Day1 group, but not in Day4 and Day7 group. Conclusions- Our results suggest that the change of host cerebral hemodynamics after stroke drastically affect the distribution of hBMSCs, which delivered intra-arterially. It is important to establish the optimal timing of intra-arterial delivery of stem cells after stroke.