title: Human neural stem cell intracerebral grafts show spontaneous early neuronal differentiation after several weeks.
abstract: Human neural stem cells (hNSCs) hold great promise for the treatment of neurological diseases. Considerable progress has been made to induce neural differentiation in the cell culture in vitro and upon transplantation in vivo [2] in order to explore restoration of damaged neuronal circuits. However, in vivo conventional strategies are limited to post mortem analysis. Here, we apply our developed first fate mapping platform to monitor neuronal differentiation in vivo by magnetic resonance imaging, bioluminescence imaging, and fluorescence imaging. Ferritin, Luciferase and GFP under neuronal-specific promoters for immature and mature neurons, respectively, were used to generate transgenic hNSCs. Differentiation-linked imaging reporter expression was validated in vitro. The time profile of spontaneous neuronal maturation after transplantation into mouse brain cortex demonstrated early neuronal differentiation within 6 weeks. Fully mature neurons expressing synaptogenesis were observed only after three months or longer. Our trimodal fate mapping strategy represents a unique non-invasive tool to monitor the time course of neuronal differentiation of transplanted stem cells in vivo.
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Tennstaedt
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Aswendt
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Adamczak
authors.affiliation: Neurobiology, University of Cologne, D-50931 Cologne, Germany.
authors.forename: Ursel
authors.initials: U
authors.lastname: Collienne
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Selt
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schneider
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Henn
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Schaefer
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, D-50931 Cologne, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Lagouge
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Wiedermann
authors.affiliation: Neurobiology, University of Cologne, D-50931 Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kloppenburg
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, D-50931 Cologne, Germany; Department of Radiology, Leiden University Medical Center, 2311 EZ Leiden, Netherlands. Electronic address: mathias@nf.mpg.de.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation; D019070:Cell Lineage; D003199:Computer Systems; D055724:Electrophysiological Phenomena; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D009474:Neurons / Q000166:cytology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D033581:Stem Cell Transplantation; D013997:Time Factors
chemical_list: D049452:Green Fluorescent Proteins
keywords: Doublecortin promoter; Human neural stem cells; In vivo bioluminescence imaging; Neuronal differentiation; Synapsin I promoter