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Molecular Imaging with Cell Tracking in the CNS

Molecular and cellular MR imaging is a rapidly growing field aiming to visualization of macromolecules and cells in living organisms (1). These techniques allow in vivo monitoring of cell transplantation, transduction and migration, and until now they have been employed mainly by researchers for evaluation of cell trafficking, correction mechanisms and therapeutic efficacy in different animal models of human diseases. However, once novel therapeutic approaches, such as cellular and gene therapies, demonstrate to be useful and safe in pre-clinical models of Central Nervous System (CNS) disorders, molecular and cellular MR imaging might play an important role also in clinical practice, since accurate delivery and/or homing of cells to target organs is crucial for clinical success. Above all, the possibility to perform longitudinal studies on living subjects makes molecular and cellular MR imaging a helpful tool in both pre-clinical and clinical settings. Neural Stem Cells (NSC) have recently raised interest because of their therapeutic potential in both cell-based and gene therapy applications. NSC are a heterogeneous population of immature progenitors, mitotically active, multipotent and self-renewing, present during development and in adult brain, both in primates and rodents (2-3). NSC can be cultured and grown in vitro, and, once transplanted in vivo, are able to generate a differentiated progeny capable of integrating and repairing the damaged neural tissue. This approach have been successfully employed in different CNS pathologies. In order to reconstitute the neural population in the substantia nigra that is progressively lost in Parkinson disease, NCS transplantation have been attempted in both animals and humans (4). NSC transplantation has been demonstrated to be useful also in animal models in traumatic lesions of the spinal cord (5), and in ischemic and hemorragic brain lesions (6,7). Further, intravenous injection of NSC induces recovery in a murine model of multiple sclerosis (8). Recent evidences suggest that endogenous neurogenesis can be exploited in adult brain in vivo for therapeutic purposes. Endogenous NSC can be modified in vivo, and thus recruited to damaged brain areas, where their progeny can differentiate and integrate in the tissue, replacing damaged or lost neurons (9-10). To this regard, the possibility to use viral vectors, such as lentiviruses (LV), to obtain sustained and long-term expression of therapeutic or trophic factors in NSC and their progeny is of particular interest (11). Knowing the location of either delivered or genetically modified NSC in cell-based or gene therapy approaches is of utmost importance to …