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

Numerous clinical and experimental studies have evaluated stem cells 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. The identification of the location, migration and biodistribution of transplanted cells and the differentiation of implanted from endogenous cells is critical for the identification of underlying mechanisms of action. 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. The long-term goal of my research is to study the potential of stem cell therapy in replacing lost neuronal elements in the brain by either transplantation of exogenous neural stem cells and/or by stimulation of endogenous stem cells from known neurogenic areas in the brain. The main goal of the work presented in this dissertation was to develop a non-invasive imaging technique using the human sodium-iodide symporter (NIS) as a reporter gene system for in vivo imaging of neural stem cells in the brain. My data show that the NIS, in combination with SPECT/CT imaging, allows for the repeated visualization of neural stem cells in vivo, and validate the use of the NIS as a safe, effective reporter gene for non-invasive imaging of stem cells after transplantation in the brain. The repeated, non-invasive tracking of implanted stem cells will contribute to a better understanding of the mechanisms of stem cell therapy and, therefore will accelerate the development of effective stem cell therapies for traumatic brain injury and other types of central nervous system injury.