Delivery of stem cells to the brain using MRIgFUS

摘要

Stem cell therapy is promising to treat neurodegenerative diseases, traumatic brain injury, and stroke. For stem cells to progress towards clinical use, the associated risks of current methods for delivery need to be reduced. Here, we introduce focused ultrasound (FUS) as a novel method for non-invasive delivery of neural stem cells to the brain. Magnetic resonance imaging (MRI) was used to target the striatum and the hippocampus on the left side for disruption of the blood-brain barrier (BBB). Definity microbubble contrast agent was injected intravenously at the onset of sonication. Following BBB disruption, green fluorescent protein (GFP)-expressing neural stem cells were injected into the carotid artery. MRI and standard post-mortem immunohistochemistry were used to detect the cells in vivo. Contrast-enhanced T1w images confirmed FUS increased BBB permeability in the targeted regions. Immunohistochemistry revealed that the cells crossed the BBB and that they were localized to the left striatum and left hippocampus. Twenty four hours after sonication, GFP-positive cells exhibited a neuronal phenotype and expressed nestin, polysialic acid and doublecortin. Together these results demonstrate that MRI-guided FUS (MRIgFUS) is an effective tool for delivery of cells to the brain. This technique may be the key to reducing the risks of cell transplantation and leading to improvements in stem cell therapy in the clinical setting.