title: Human adult white matter progenitor cells are multipotent neuroprogenitors similar to adult hippocampal progenitors.
abstract: Adult neural progenitor cells (aNPC) are a potential autologous cell source for cell replacement in neurologic diseases or for cell-based gene therapy of neurometabolic diseases. Easy accessibility, long-term expandability, and detailed characterization of neural progenitor cell (NPC) properties are important requisites for their future translational/clinical applications. aNPC can be isolated from different regions of the adult human brain, including the accessible subcortical white matter (aNPCWM), but systematic studies comparing long-term expanded aNPCWM with aNPC from neurogenic brain regions are not available. Freshly isolated cells from subcortical white matter and hippocampus expressed oligodendrocyte progenitor cell markers such as A2B5, neuron-glial antigen 2 (NG2), and oligodendrocyte transcription factor 2 (OLIG2) in ∼20% of cells but no neural stem cell (NSC) markers such as CD133 (Prominin1), Nestin, SOX2, or PAX6. The epidermal growth factor receptor protein was expressed in 18% of aNPCWM and 7% of hippocampal aNPC (aNPCHIP), but only a small fraction of cells, 1 of 694 cells from white matter and 1 of 1,331 hippocampal cells, was able to generate neurospheres. Studies comparing subcortical aNPCWM with their hippocampal counterparts showed that both NPC types expressed mainly markers of glial origin such as NG2, A2B5, and OLIG2, and the NSC/NPC marker Nestin, but no pericyte markers. Both NPC types were able to produce neurons, astrocytes, and oligodendrocytes in amounts comparable to fetal NSC. Whole transcriptome analyses confirmed the strong similarity of aNPCWM to aNPCHIP. Our data show that aNPCWM are multipotent NPC with long-term expandability similar to NPC from hippocampus, making them a more easily accessible source for possible autologous NPC-based treatment strategies.
authors.affiliation: Division of Neurodegenerative Diseases, Department of Neurology, and Department of Neurosurgery, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Department of Neurology, Hannover Medical School, Hannover, Germany; Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany; Department of Neurology, Technical University of Munich, Munich, Germany; Division of Biology, California Institute of Technology, Pasadena, California, USA; Center for Regenerative Therapies Dresden, Dresden, Germany.
authors.forename: Xenia
authors.initials: X
authors.lastname: Lojewski
authors.forename: Andreas
authors.initials: A
authors.lastname: Hermann
authors.forename: Florian
authors.initials: F
authors.lastname: Wegner
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Araúzo-Bravo
authors.forename: Susanne
authors.initials: S
authors.lastname: Hallmeyer-Elgner
authors.forename: Matthias
authors.initials: M
authors.lastname: Kirsch
authors.forename: Johannes
authors.initials: J
authors.lastname: Schwarz
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation
keywords: Fetal neural stem cells; Hippocampus; Human adult brain; Neural progenitor cells; White matter