title: Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.
abstract: Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Stem Cell Biology and Regeneration Group, Institute of Cell Biology, ZMBE, Westfälische Wilhelms-University Münster, 48149 Münster, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hemmer
authors.affiliation: Laboratory for Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Laboratory for Molecular Psychiatry, Westfälische Wilhelms-University of Münster, 48149 Münster, Germany.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Stem Cell Biology and Regeneration Group, Institute of Cell Biology, ZMBE, Westfälische Wilhelms-University Münster, 48149 Münster, Germany.
authors.forename: Thea
authors.initials: T
authors.lastname: van Wüllen
authors.affiliation: Stem Cell Biology and Regeneration Group, Institute of Cell Biology, ZMBE, Westfälische Wilhelms-University Münster, 48149 Münster, Germany; Laboratory for Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Laboratory for Molecular Psychiatry, Westfälische Wilhelms-University of Münster, 48149 Münster, Germany.
authors.forename: Marna
authors.initials: M
authors.lastname: Sakalem
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Tapia
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Aidos
authors.initials: A
authors.lastname: Baumuratov
authors.affiliation: Molecular Neurobiology, Faculty of Biology, University of Bielefeld, 33501 Bielefeld, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kaltschmidt
authors.affiliation: Molecular Neurobiology, Faculty of Biology, University of Bielefeld, 33501 Bielefeld, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kaltschmidt
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: Laboratory for Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Laboratory for Molecular Psychiatry, Westfälische Wilhelms-University of Münster, 48149 Münster, Germany.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Stem Cell Biology and Regeneration Group, Institute of Cell Biology, ZMBE, Westfälische Wilhelms-University Münster, 48149 Münster, Germany. Electronic address: jens.schwamborn@uni.lu.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Schwamborn
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001921:Brain / Q000166:cytology*; D002470:Cell Survival; D002478:Cells, Cultured; D055724:Electrophysiological Phenomena; D005260:Female; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology; D009836:Oligodendroglia / Q000166:cytology