Direct vs. IV BMSC Delivery

Background: Recent studies have indicated that bone marrow stromal cells (BMSC) may improve neurological function when transplanted into animal model of central nervous system (CNS) disorders including cerebral infarct. However, there are few studies that evaluate the therapeutic benefits of direct and intravenous BMSC transplantation for cerebral infarct. Objective: This study was aimed to clarify the favorable route of cell delivery for cerebral infarct in rats. Methods: The rats were subjected to permanent middle cerebral artery occlusion. The BMSC were labeled with near infrared (NIR)-emitting quantum dots, and were transplanted directly (1×10^7 cells) or intravenously (3×10^7 cells) at 7 days after the insult. Using in vivo NIR fluorescence imaging technique, the behaviors of BMSC were serially visualized during 4 weeks after transplantation. Motor function was also assessed. Immunohistochemistry was performed to evaluate the fate of the engrafted BMSC. Results: Direct, but not intravenous, transplantation of BMSC significantly enhanced functional recovery. In vivo NIR fluorescence imaging could clearly visualize their migration towards cerebral infarct during 4 weeks after transplantation in direct group, but not in intravenous, group. The BMSC were widely distributed in the ischemic brain and some of them expressed neural cell markers in the direct group, but not in the intravenous group. Conclusion: These findings strongly suggest that intravenous administration of BMSC has limited effectiveness at clinically relevant timing and direct administration should be chosen for patients with ischemic stroke, although further studies would be warranted to establish the treatment protocol