Because many of the most severe brain diseases and injuries involve damage to or death of brain cells, cell based therapies to repair the brain are attractive. Traditionally, cellular therapy has been conceived to entail injections or transplants of exogenous cells into recipients, either within or adjacent to the insult, or systemically. However, endogenous stem cell niches have been characterized, both in animals and in humans, and may present a therapeutic reservoir for cellular therapy. Here I propose innovative methods for steering large numbers of endogenous neural progenitor cells to areas of experimental stroke in somatosensory cortex in rodents. The stroke model will be the endothelin-1 induced vasoconstriction model. Following the stroke, neural progenitor cells will be labeled with MRI contrast agent directly in vivo. Next, these endogenous stem cells will be chemically manipulated, in vivo, first enhancing stem cell proliferation, then directing the migration of neuroblasts to stroke sites. In vivo cell tracking will be performed using high resolution magnetic resonance imaging, allowing the monitoring of therapeutic progress both spatially and longitudinally. Imaging data will be correlated to immunohistochemistry. Functional magnetic resonance imaging will be used to investigate restoration of function in the stroke sites due to the experimental therapeutic regiment and will be compared to standard behavioral assessments. If successful, significant impact can be achieved on stem cell therapy by realizing the full potential of a relatively unexplored source of therapeutic stem cells, the endogenous stem cells. However, equally important will be the further development and refinement of MRI methods for detecting single cells, in vivo. It is clear that cell therapy in humans will be greatly aided by the use of non-invasive methods for monitoring cell position and fate. The magnetic resonance imaging methods developed here will facilitate and expedite eventual human clinical applications.
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