targeted delivery of neural stem cells to the brain using mri-guided focused ultrasound to disrupt the blood-brain barrier神经干细胞的靶向大脑使用mri引导下的聚焦超声破坏血脑屏障.pdf

Targeted Delivery of Neural Stem Cells to the Brain Using MRI-Guided Focused Ultrasound to Disrupt the Blood- Brain Barrier 1 2,3 1 ˜ 1,2,4 2,4. Alison Burgess *, Carlos A. Ayala-Grosso , Milan Ganguly , Jessica F. Jordao , Isabelle Aubert , Kullervo Hynynen1,5. 1 Imaging Research, Sunnybrook Research Institute, Toronto, Ontario, Canada, 2 Brain Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada, 3 Laboratorio de Patologia Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela, 4 Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, 5 Medical Biophysics, University of Toronto, Toronto, Ontario, Canada Abstract Stem cell therapy is a promising strategy to treat neurodegenerative diseases, traumatic brain injury, and stroke. For stem cells to progress towards clinical use, the risks associated with invasive intracranial surgery used to deliver the cells to the brain, needs to be reduced. Here, we show that MRI-guided focused ultrasound (MRIgFUS) is a novel method for non- invasive delivery of stem cells from the blood to the brain by opening the blood brain barrier (BBB) in specific brain regions. We used MRI guidance to target the ultrasound beam thereby delivering the iron-labeled, green fluorescent protein (GFP)- expressing neural stem cells specifically to the striatum and the hippocampus of the rat brain. Detection of cellular iron using MRI established that the cells crossed the BBB to enter the brain. After sacrifice, 24 hours later, immunohistochemical analysis confirmed the presence of GFP-positive cells in the targeted brain regions.