Imaging remyelination in the central nervous system. (360G-Wellcome-107239_Z_15_Z)

There are currently no outcome measures that provide direct evidence for the differentiation of oligodendrocyte progenitor cells (OPCs) into remyelinating oligodendrocytes in vivo. The aim of this project is to image differentiation of endogenous and transplanted OPCs into remyelinating oligodendrocytes in vivo. This will be achieved by developing a molecular imaging strategy in which differentiating progenitor cells express organic anion transporting polypeptide (oatp), which allows upta ke of gadohexate for detection by T1-weighted MRI, or luciferin for detection by bioluminescence, in models of CNS de/remyelination. I will use lentiviral vectors to express oatp in OPCs as they differentiate by controlling oatp expression using an MBP promoter. These vectors will be used to transfect cultured OPCs which will be transplanted into areas of CNS demyelination, or transfect endogenous OPCs in areas of demyelination undergoing spontaneous remyelination. Some cells labelled in vi tro will be co-labeled with SPIO. Animals receiving transfected cells or virus will receive systemic gadoxetate. Oatp expressing cells will be detected with 9.4T T1 MRI (and T2 for cells co labelled with SPIO).