In Vivo Imaging of Transplanted Stem Cells In The Brain
Principle Investigator: Maria Micci, PhD.
Co-investigators: Douglas Dewitt, Massoud Motamedi
Stem cells represent a promising therapeutic approach for several neurological disorders of the central nervous system (i.e. Parkinson’s disease), as well as for traumatic brain injury (TBI). The successful development of stem cell therapy, and its translation to the clinical setting, is currently hampered by the lack of a reliable and safe method to accurately monitor the location, migration and phenotypical differentiation of transplanted cells. The long term-goal of our work is to develop a non-invasive imaging technique to facilitate the development of cell-replacement therapy for clinical use. In this application, will use the human sodium-iodide symporter (hNIS) as a reporter gene system for in vivo imaging of neural stem cells (NSC) in the brain. Our preliminary data show that the hNIS, in combination with SPECT/CT imaging, allows for the repeated visualization of NSC in vivo. The NIS is normally expressed in the thyroid, stomach, choroids plexus and salivary gland, but not in the brain. Previous studies have shown that the hNIS can be used as a reporter gene to track grafted cells in vivo in the heart. Currently, no studies have been performed to explore the use of the hNIS to track grafted NSC in the brain.
In this proposal we will pursue the following specific aims.
- To characterize human-derived neural stem cells (hNSC) expressing the hNIS in vitro
- To track the location and survival of hNSC-hNIS after transplantation in a rat model of TBI.
The completion of the proposed aims will validate the use of the hNIS 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 TBI and other types of central nervous system injury.