ABSTRACT
A key player of brain regeneration are neural stem cells (NSCs), which reside during adulthood in specific brain niches and possess the unique feature among brain cells to retain the capacity to proliferate and give rise to new neurons and glia, for example, in response to injuries.Regenerative medicine for neurological diseases like Parkinson’s disease and stroke, in which certain brain regions are lost, is focusing on the role of endogenous as well as transplanted stem cells as a novel treatment strategy. With 19F MRI, researchers now have a tool in hand to visualize how and when engrafted NSCs migrate and repopulate the injured brain regions in vivo. This represents a clear advantage compared to conventional, invasive studies which depend on subgroups of animals for each individual time point to reveal recovery mechanisms as the benefit of the engrafted stem cells. In contrast, 19F MRI requires a lower number of laboratory animals used for a single experiment while providing the intra-individual time profile. This book chapter introduces (i) the application of 19F MRI for imaging NSCs in regenerative therapies, (ii) the strategy of efficient labeling NSCs with 19F MRI contrast agents, (iii) the in vitro and in vivo imaging protocols, and, finally, (iv) the 19F MRI-specific post-processing and validation steps for imaging cell grafts in the rodent brain. 10.2 Neural Stem Cells Used for Cell Therapy
Neural stem cells comprise a specific primordial and the least committed cell type of the central nervous system (CNS). In contrast to the more limited progenitor and precursor cells, a single NSC is defined to be (i) multipotent (differentiation in neurons, astrocytes, and oligodendrocytes is possible), (ii) able to repopulate a developing or degenerated region of the CNS, and (iii) able to self-renew (to produce daughter cells with identical properties) [1]. NSCs reside throughout adulthood in at least two neurogenic niches in mammals (Fig. 10.1), including the lateral ventricle wall (subventricular zone, SVZ) and the dentate gyrus of the hippocampus (subgranular zone, SGZ) [2]. In rodents they
possess a very high proliferative rate of 10,000 to 30,000 (SVZ) and 9,000 cells (SGZ) per day [3, 4]. NSCs differentiate into neuronal precursor cells, so called neuroblasts, which migrate from the SVZ and SGZ towards the olfactory bulb (rodents), and striatum (human) and granular zone of the hippocampus (rodents/human), respectively [5-7]. These cells provide a source of new neurons, a continuous process which is called neurogenesis. Neurogenesis is regulated according to external stimuli, e.g., learning, activity, environmental enrichment and olfactory sensors [8-11] as well as pathophysiological triggers. Most importantly, NSCs respond to severe CNS injuries, e.g., stroke, traumatic brain injury and Alzheimer’s disease [12-14] as part of an endogenous regeneration cascade.
