Development of a novel imaging system for cell therapy in the brain

Maria-Adelaide Micci, Debbie R. Boone, Margaret A. Parsley, Jingna Wei, Igor Patrikeev, Massoud Motamedi, Helen L. Hellmich

Stem cells have been evaluated as a potential therapeutic approach for several neurological disorders of the central and peripheral nervous system as well as for traumatic brain and spinal cord injury. Currently, the lack of a reliable and safe method to accurately and non-invasively locate the site of implantation and track the migration of stem cells in vivo hampers the development of stem cell therapy and its clinical application. In this report, we present data that demonstrate the feasibility of using the human sodium-iodide symporter (hNIS) as a reporter gene for tracking neural stem cell (NSC) after transplantation in the brain using SPECT/CT imaging. Neural stem cells were isolated from the hippocampus of adult rats (Hipp-NSC) and transduced with a lentiviral vector containing the hNIS gene. Hipp-NSC expressing the hNIS (NIS-Hipp-NSC) were characterized in vitro and in vivo after transplantation in the rat brain and imaged using technetium 99 m ((99m)Tc) and a small rodent SPECT/CT apparatus. Comparisons were made between Hipp-NSC and NIS-Hipp-NSC, and statistical analysis was performed using two-tailed Student's t test. Our results show that the expression of the hNIS allows for the repeated visualization of NSC in vivo in the brain using SPECT/CT imaging and it does not affect the ability of Hipp-NSC to generate neuronal and glial cells in vitro and in vivo. These data support the use of the hNIS as a reporter gene for non-invasive imaging of NSC in the brain. The repeated, non-invasive tracking of implanted cells will accelerate the development of effective stem cell therapies for TBI and other types of central nervous system injury.