Bidirectional Enhancement of Cell Proliferation Between Iron Oxide Nanoparticle-Labeled Mesenchymal Stem Cells and Choroid Plexus in a Cell-Based Therapy Model of Ischemic Stroke

PURPOSE: Stem cell therapy for ischemic stroke has shown success in experimental settings, but its translation into clinical practice is challenging. The choroid plexus (CP) plays a regulatory role in neural regeneration. Mesenchymal stem cells (MSCs) promote neurogenesis in the ventricular–subventricular zone. However, it is unclear whether MSCs interact with the CP in brain tissue repair. METHODS: Rat (r)MSCs were labeled with iron oxide nanoparticles (IONs) and transduced with red fluorescent protein, and then injected into the brain of rats with ischemic stroke and monitored over time by magnetic resonance imaging. The functional recovery of rats was determined by the corner test score, Modified Neurological Severity score, and stroke volume. MSCs and CP were also co-cultured for 14 days, and the medium was analyzed with a cytokine array. RESULTS: In vivo imaging and histologic analysis revealed that ION-labeled MSCs were mainly located at the injection site and migrated to the infarct area and to the CP. Functional recovery was greater in rats treated with MSCs as compared to those that received mock treatment. Bidirectional enhancement of proliferation in MSCs and CP was observed in the co-culture; moreover, MSCs migrated to the CP. Cytokine analysis revealed elevated levels of proliferation- and adhesion-related cytokines and chemokines in the culture medium. Wikipathway predictions indicated that insulin-like growth factor 1/Akt signaling (WP3675), chemokine signaling pathway (WP2292), and spinal cord injury (WP2432) are involved in the increased proliferation and migration of MSCs co-cultured with the CP. CONCLUSION: Crosstalk with the CP enhances MSC proliferation and migration in a transwell assay. Moreover, MRI reveals MSC migration towards the CP in an ischemic stroke model. The secreted factors resulting from this interaction have therapeutic potential for promoting functional recovery in the brain after ischemic stroke.