In situ labeling and imaging of endogenous neural stem cell proliferation and migration.

Endogenous neural stem cells (eNSCs) reside in defined regions of the adult brain and have the potential to generate new brain cells, including neurons. Stimulation of adult neurogenesis presents an enormous potential for regenerative therapies in the central nervous system. However, the methods used to monitor the proliferation, migration, differentiation, and functional integration of eNSCs and their progeny are often invasive and limited in studying dynamic processes. To overcome this limitation, novel techniques and contrast mechanisms for in vivo imaging of neurogenesis have recently been developed and successfully applied. In vivo labeling of endogenous neuronal progenitor cells in situ with contrast agents or tracers enables longitudinal visualization of their proliferation and/or migration. Labeling of these cells with magnetic nanoparticles has proven to be very useful for tracking neuroblast migration with MRI. Alternatively, genetic labeling using reporter gene technology has been demonstrated for optical and MR imaging, leading to the development of powerful tools for in vivo optical imaging of neurogenesis. More recently, the iron storage protein ferritin has been used as an endogenously produced MRI contrast agent to monitor neuroblast migration. The use of specific promoters for neuronal progenitor cell imaging increases the specificity for visualizing neurogenesis. Further improvements of detection sensitivity and neurogenesis-specific contrast are nevertheless required for each of these imaging techniques to further improve the already high utility of this toolbox for preclinical neurogenesis research.