title: Rapid and robust generation of long-term self-renewing human neural stem cells with the ability to generate mature astroglia.
abstract: Induced pluripotent stem cell bear the potential to differentiate into any desired cell type and hold large promise for disease-in-a-dish cell-modeling approaches. With the latest advances in the field of reprogramming technology, the generation of patient-specific cells has become a standard technology. However, directed and homogenous differentiation of human pluripotent stem cells into desired specific cell types remains an experimental challenge. Here, we report the development of a novel hiPSCs-based protocol enabling the generation of expandable homogenous human neural stem cells (hNSCs) that can be maintained under self-renewing conditions over high passage numbers. Our newly generated hNSCs retained differentiation potential as evidenced by the reliable generation of mature astrocytes that display typical properties as glutamate up-take and expression of aquaporin-4. The hNSC-derived astrocytes showed high activity of pyruvate carboxylase as assessed by stable isotope assisted metabolic profiling. Moreover, using a cell transplantation approach, we showed that grafted hNSCs were not only able to survive but also to differentiate into astroglial in vivo. Engraftments of pluripotent stem cells derived from somatic cells carry an inherent tumor formation potential. Our results demonstrate that hNSCs with self-renewing and differentiation potential may provide a safer alternative strategy, with promising applications especially for neurodegenerative disorders.
authors.affiliation: Stem Cell Biology and Regeneration Group, Institute of Cell Biology (ZMBE), Westfälische Wilhelms-Universität Münster, 48149 Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Palm
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Belval, Luxembourg.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolognin
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Belval, Luxembourg.
authors.forename: Johannes
authors.initials: J
authors.lastname: Meiser
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Belval, Luxembourg.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nickels
authors.affiliation: Stem Cell Biology and Regeneration Group, Institute of Cell Biology (ZMBE), Westfälische Wilhelms-Universität Münster, 48149 Münster, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Träger
authors.affiliation: Stem Cell Biology and Regeneration Group, Institute of Cell Biology (ZMBE), Westfälische Wilhelms-Universität Münster, 48149 Münster, Germany.
authors.forename: Ralf-Leslie
authors.initials: RL
authors.lastname: Meilenbrock
authors.affiliation: Institute of Anatomy and Molecular Neurobiology, Westfälische-Wilhelms University, Münster, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brockhaus
authors.affiliation: Institute of Anatomy and Molecular Neurobiology, Westfälische-Wilhelms University, Münster, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Schreitmüller
authors.affiliation: Institute of Anatomy and Molecular Neurobiology, Westfälische-Wilhelms University, Münster, Germany.|Cluster of Excellence EXC 1003, Cells in Motion, CiM, Münster, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Missler
authors.affiliation: Stem Cell Biology and Regeneration Group, Institute of Cell Biology (ZMBE), Westfälische Wilhelms-Universität Münster, 48149 Münster, Germany.|Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Belval, Luxembourg.
authors.forename: Jens Christian
authors.initials: JC
authors.lastname: Schwamborn
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058953:Neural Stem Cells / Q000166:cytology*