Abstract 119: Bone Marrow Stromal Cell Transplantation Enhances Recovery of Local Glucose Metabolism after Cerebral Infarct in Rats: A 18 F-FDG PET Study

Abstract

Background: Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurologic function when transplanted into animal models of central nervous system disorders. However, no methods have been established to objectively evaluate the beneficial effect of BMSC transplantation on the host brain in clinical situation. Therefore, this study was aimed to assess whether the BMSC significantly improve local glucose metabolism in the peri-infarct area on 18 F-fluorodeoxyglucose (FDG) PET, when transplanted into the infarct brain of rats. Methods: The BMSC were harvested from green fluorescent protein (GFP)-transgenic rats and were cultured. The rats were subjected to permanent middle cerebral artery (MCA) occlusion. The BMSC or vehicle was transplanted into the ipsilateral striatum at 7 days after the onset of MCA occlusion. Using 18 F-FDG PET, local glucose metabolism was semi-quantitatively and serially measured at 6 days post-ischemia and at 4 weeks after BMSC transplantation. Motor function was serially evaluated throughout the experiments. The distribution and fate of engrafted cells were examined, using fluorescence immunohistochemistry at 4 weeks after BMSC transplantation. Simultaneously, the expression of brain-type glucose transporter (GLUT1 and GLUT3) was also evaluated. Results: Local glucose metabolism was significantly lower in the dorsal peri-infarct neocortex at 6 days post-ischemia. However, BMSC transplantation significantly accelerated the recovery of local glucose metabolism in that area at 4 weeks after transplantation. Thus, the ratio of glucose metabolism in the ipsilateral to contralateral dorsal neocortex significantly increased from 72.5 ± 4.2% to 78.7 ± 4.0% in the vehicle group (P<0.01). On the other hands, the values more pronouncedly increased from 72.7 ± 4.4% to 87.7 ± 5.3% in the BMSC group (P<0.01). The BMSC were engrafted in the boundary zone of cerebral infarct and also expressed the phenotypes of neural cells. BMSC transplantation significantly prevented the overexpression of GLUT1 in the endothelium and of GLUT3 in the neurons in that area. Conclusion: These findings strongly suggest that BMSC may enhance the recovery of local glucose metabolism in the peri-infarct area when directly transplanted into the infarct brain at clinically relevant timing. The recovery of local glucose metabolism may inhibit pathological upregulation of GLUT1 and GLUT3. 18 F-FDG PET may be the candidate of valuable modalities to scientifically prove the beneficial effects of BMSC transplantation on the host brain in clinical situation.