EN
Taking advantage of recent developments in molecular biology and imaging, we have developed a system for monitoring status of transplanted cells non-invasively. We use high-resolution MRI to acquire information about the position of grafted cells and reporter gene-based bioluminescent imaging (BLI) to monitor their survival and differentiation. Here, we report on two different approaches for the in vivo imaging of glial precursors cells (GRPs). Approach I: Monitoring of the targeted, intravascular cerebral delivery of GRPs. Cells were engineered to express VLA-4 integrin (to enhance vascular adhesion) and were labeled with the MR contrast agent Feridex. Recipient rats were injected i.p. with lipopolysaccharide, a known inducer of endothelial VCAM-1 expression, and the cells were infused into the carotid artery. MRI demonstrated extensive hypointense regions, indicating successful targeting. Approach II: Monitoring of the survival and differentiation of intracerebrally injected GRPs. Cells were engineered to express luciferase under the control of a constitutive or the cell-type-specifi c promoters and were injected into the brain of immunodefi cient or immunocompetent mice. BLI demonstrated that transplanted GRPs survived for extended periods of time in immunodefi cient animals, while, in immunocompetent animals, rejection was initiated two weeks after grafting. With cell type-specifi c promoters, we were able to visualize the process of glial differentiation in vivo.