Intra-Arterial Transplantation of Stem Cells in Large Animals – A Minimally-Invasive Strategy for the Treatment of Disseminated Neurodegeneration
Abstract Stem cell transplantation proved promising in animal models of neurological diseases; however, in conditions with disseminated pathology such as ALS, delivery of cells and their broad distribution is challenging. To address this problem, we explored intra-arterial (IA) delivery route of stem cells. The goal of this study was to investigate the feasibility and safety of MRI-guided transplantation of glial restricted precursors (GRPs) and mesenchymal stem cells (MSCs) in dogs suffering from ALS-like disease, degenerative myelopathy (DM). Three naïve pigs were used for MSC transplantation as a pre-treatment control before transplantation in dogs. Cells were labeled with iron oxide nanoparticles. For IA transplantation a 1.2-French microcatheter was advanced into the middle cerebral artery under roadmap guidance. Then, the cells were transplanted under real-time MRI with the acquisition of dynamic T2*-weighted images. Interventional and follow-up MRI proved the procedure was feasible and safe. The transplantation of canine GRPs resulted in rather poor retention in the brain, whereas canine MSCs demonstrated excellent settlement. Notably, histopathology showed the successful and predictable placement of transplanted porcine MSCs. Analysis of gene expression after transplantation revealed a reduction of inflammatory factors, which may indicate a promising therapeutic strategy in the treatment of neurodegenerative diseases.