title: In Vivo Fate Imaging of Intracerebral Stem Cell Grafts in Mouse Brain.
abstract: We generated transgenic human neural stem cells (hNSCs) stably expressing the reporter genes Luciferase for bioluminescence imaging (BLI) and GFP for fluorescence imaging, for multimodal imaging investigations. These transgenic hNSCs were further labeled with a clinically approved perfluoropolyether to perform parallel 19F MRI studies. In vitro validation demonstrated normal cell proliferation and differentiation of the transgenic and additionally labeled hNSCs, closely the same as the wild type cell line, making them suitable for in vivo application. Labeled and unlabeled transgenic hNSCs were implanted into the striatum of mouse brain. The time profile of their cell fate after intracerebral grafting was monitored during nine days following implantation with our multimodal imaging approach, assessing both functional and anatomical condition. The 19F MRI demarcated the graft location and permitted to estimate the cell number in the graft. BLI showed a pronounce cell loss during this monitoring period, indicated by the decrease of the viability signal. The in vivo obtained cell fate results were further validated and confirmed by immunohistochemistry. We could show that the surviving cells of the graft continued to differentiate into early neurons, while the severe cell loss could be explained by an inflammatory reaction to the graft, showing the graft being surrounded by activated microglia and macrophages. These results are different from earlier cell survival studies of our group where we had implanted the identical cells into the same mouse strain but in the cortex and not in the striatum. The cortical transplanted cells did not show any loss in viability but only pronounced and continuous neuronal differentiation.
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Tennstaedt
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Cologne, Germany.|Scientific Direction Unit, IRCCS Foundation Neurological Institute "C. Besta", Milan, Italy.|Politecnico di Milano, Department of Electronic Information and Bioengineering, Milan, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mastropietro
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Nelles
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beyrau
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Cologne, Germany.|Department Radiology, Leiden University Medical Center, Leiden University, Leiden, Netherlands.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology*; D005462:Fluorine Radioisotopes; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D049409:Luciferases, Firefly / Q000235:genetics; D008163:Luminescent Measurements / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008819:Mice, Nude; D064847:Multimodal Imaging / Q000379:methods; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D019076:Transgenes; D014183:Transplantation, Heterologous
chemical_list: D005462:Fluorine Radioisotopes; D049452:Green Fluorescent Proteins; D049409:Luciferases, Firefly