This proposal has a technology development component and a basic immunobiological component. It consists of three Specific Aims: (1) development of novel intracellular MRI agents and associated cell labeling protocols, and measurement of the cell labeling efficiency and lifetime; (2) biological characterizations via quantitative cytotoxicity, proliferation, and immunological assays of labeled immune cells, such as dendritic cells (DCs) and macrophages; and (3) in vivo studies where labeled immune cells will be injected into NOD mice and imaged using extremely-high field (11.7 T) MRI. We will visualize the biodistribution of the labeled cells following intravenous inoculation and the time-lapse cell migration following focal injection into specific tissue sites. We will test the hypothesis that different subsets of DCs have different migratory patterns in vivo based on their maturation state. Using the NOD mouse we will test the hypothesis that the ability of mature DCs to prevent diabetes is dependent, in part, on their migratory capacity. A long-term application of this technology is monitoring the trafficking of cellular therapeutics in vivo. The proposed research project is highly interdisciplinary, and we have assembled a diverse team of investigators in the Pittsburgh area with expertise in in vivo magnetic resonance microscopy (Ahrens), immunology (Morel) and biological reagent design (Ernst/Waggoner).
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