Enhancement of FUS Mediated Delivery of Stem Cells to Brain

Project Name: Enhancement of FUS Mediated Delivery of Stem Cells to Brain
Status: Complete
Primary Site: University of Maryland School of Medicine
Sponsor Organization: Focused Ultrasound Foundation
Funded Date: Apr 01, 2016
Funding Period: Apr 01, 2016 - Mar 31, 2018
Funding Program: Research Award
Category: Pre-Clinical
Amount Awarded: $203,000.00


We propose that magnetic targeting of super-paramagnetic iron oxide nanoparticles (SPION) labeled cells will enhance the delivery of stem cells to brain after focused ultrasound (FUS) mediated opening of the blood-brain barrier (BBB). FUS mediated opening of the BBB allowing stem cells to enter the brain from the blood is a remarkable advance in delivery of stem cell therapeutics over current invasive methods of brain injection. However the efficiency of cellular entry is low. SPIONs are taken up by stem cells, allowing for labeling of transplanted stem cells in brain both with histology and MRI. Our research shows that SPION labeled stem cells show enhanced brain retention near a magnet on the skull, in a rat model of traumatic brain injury. There is no experience combining these two minimally invasive strategies to deliver stem cells to the brain. We will assess the capacity of an external magnet to enhance the efficiency of delivery to brain of SPION loaded stem cells after transient opening of the BBB using FUS. We will evaluate SPION loaded neural stem cells delivered by intravenous infusion in rats that have undergone MRI targeted FUS opening of the BBB along with a magnet placed over the skull of the sonicated hemisphere, to animals with FUS alone. The number and distribution of stem cells will be quantitative for each group to assess enhancement of delivery of stem cells after BBB opening using FUS by the addition of SPION loading and an external magnet.

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