Abstract TP110: Bone Marrow Stromal Cells Enhance The Recovery of Peri-infarct Neuronal Integrity by Replacing The Damaged Neurons - A Serial 123 I-Iomazenil SPECT Study

Abstract

Background: There is increasing evidence that bone marrow stromal cells (BMSC) have the potential to improve neurologic function when transplanted into the infarct brain. However, no methods have been established to objectively evaluate the effect of BMSC transplantation in clinical situation. Therefore, we aimed to assess whether the BMSC improve the neuronal viability on 123 I-iomazenil (IMZ) SPECT, when transplanted into the infarct brain of rats. Methods: The BMSC were harvested from rats and were cultured. The rats were subjected to permanent middle cerebral artery occlusion. The BMSC or vehicle was transplanted into the ipsilateral striatum at 7 days after the insult. Using 123 I-IMZ SPECT, The 123 I-IMZ uptake was measured at a day before and at 4 weeks after BMSC transplantation. The distribution of engrafted cells and the expression of neuron-specific γ-aminobutyric acid (GABA) receptor protein in the peri-infarct area were examied, using fluorescence immunohistochemistry. Results: The 123 I-IMZ uptake was markedly low in the dorsal peri-infarct neocortex at a day before transplantation. However, BMSC transplantation significantly improved the 123 I-IMZ uptake in that area at 4 weeks after transplantation. The ratio of 123 I-IMZ uptake in the ipsilateral to contralateral dorsal neocortex significantly increased from 53.4 ± 17.3% to 77.3 ± 16.3% in the BMSC group (P<0.01). On the other hands, the values did not change significantly in the vehicle group. The ratio of the GABA A receptor-positive cells in the ipsilateral to contralateral dorsal neocortex was significantly higher in the BMSC group than in the vehicle group (P<0.01). Conclusion: These findings strongly suggest that BMSC may improve the peri-infarct neuronal integrity when transplanted into the infarct brain at clinically relevant timing. 123 I-IMZ SPECT may be a valuable modality to scientifically prove the beneficial effects of BMSC transplantation on the host brain in clinical situation.