Abstract
The study of neurogenesis and neural progenitor cells (NPCs) is important across the biomedical spectrum, from learning about normal brain development and studying disease to engineering new strategies in regenerative medicine. In adult mammals, NPCs proliferate in two main areas of the brain, the subventricular zone (SVZ) and the subgranular zone, and continue to migrate even after neurogenesis has ceased within the rest of the brain. In healthy animals, NPCs migrate along the rostral migratory stream (RMS) from the SVZ to the olfactory bulb, and in diseased animals, NPCs migrate toward lesions such as stroke and tumors. Here we review how MRI-based cell tracking using iron oxide particles can be used to monitor and quantify NPC migration in the intact rodent brain, in a serial and relatively non-invasive fashion. NPCs can either be labeled directly in situ by injecting particles into the lateral ventricle or RMS, where NPCs can take up particles, or cells can be harvested and labeled in vitro, then injected into the brain. For in situ labeling experiments, the particle type, injection site, and image analysis methods have been optimized and cell migration toward stroke and multiple sclerosis lesions has been investigated. Delivery of labeled exogenous NPCs has allowed imaging of cell migration toward more sites of neuropathology, which may enable new diagnostic and therapeutic opportunities for as-of-yet untreatable neurological diseases.
Highlights
Magnetic resonance imaging of endogenous neural progenitor cell (NPC) is accomplished by magnetically labeling proliferating NPCs in situ and using magnetic resonance imaging (MRI) to serially monitor migration away from the subventricular zone (SVZ); in healthy animals, cells travel along the rostral migratory stream (RMS) to the olfactory bulb (OB), disease stimulates these cells to migrate away from the RMS and toward lesions in the brain
There are various sources of NPC that can be used for this purpose (Table 2): they can be isolated from the SVZ of adult rodents (e.g., Zhang et al, 2003; Jiang et al, 2005), immortalized cell lines isolated from embryonic rodent brain (e.g., Hoehn et al, 2002; Guzman et al, 2008; Obenaus et al, 2011), and human NPC can be isolated from human fetal tissue
In situ labeling with iron oxide particles is achieved by direct injection of particles into the lateral ventricle, these particles are phagocytosed by NPC in the SVZ and carried within the cells as they migrate to the OB
Summary
The study of neurogenesis and neural progenitor cells (NPCs) is important across the biomedical spectrum, from learning about normal brain development and studying disease to engineering new strategies in regenerative medicine. NPCs migrate along the rostral migratory stream (RMS) from the SVZ to the olfactory bulb, and in diseased animals, NPCs migrate toward lesions such as stroke and tumors. For in situ labeling experiments, the particle type, injection site, and image analysis methods have been optimized and cell migration toward stroke and multiple sclerosis lesions has been investigated. Delivery of labeled exogenous NPCs has allowed imaging of cell migration toward more sites of neuropathology, which may enable new diagnostic and therapeutic opportunities for as-of-yet untreatable neurological diseases
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