Tracking of administered progenitor cells in brain injury and stroke by magnetic resonance imaging

Traumatic brain injury and stroke remain important causes of chronic neurologic morbidity due to the lack of vasculature in injured brain. Promising data from preclinical and clinical studies suggest that transplantation of exogenous hematopoietic stem cells (HSCs) and neural progenitor cells (NPCs) has therapeutic potential for boosting brain repair. This neuroregeneration could be achieved by HSCs/NPCs migration, differentiation, enhanced endogenous angiogenesis and neurogenesis, and the secretion of trophic factors by these cells in injured tissue and stroke. The neuroregeneration is achieved by significant decrease in graft-versus-host disease and improved functional behavior of damaged brain. Importantly, these stem cells are derived from peripheral blood, umbilical cord blood (UCB), bone marrow (BM), and embryonic sources. A subpopulation of CD34<Superscript>+</Superscript> human HSCs identified by the cell-surface molecule AC133 (CD133) has been shown to be more specific for endothelial differentiation and vascular repair. Similarly, NPCs have shown to induced angiogenesis and neurogenesis in stroke. Several studies have been exploited in vivo imaging modalities, importantly magnetic resonance imaging (MRI) to monitor the migration and engraftment efficacy of administered cells for cell-based therapies. This chapter covers the characterization of contrast agents, cell-labeling methods for MRI, use of endothelial progenitor cells (EPCs) and NPCs in vascular integrity and neuroregeneration, and molecular mechanisms of their homing to the injured or stroke site, such as their interaction with brain endothelium as depicted by MRI.