title: L-MYC Expression Maintains Self-Renewal and Prolongs Multipotency of Primary Human Neural Stem Cells.
abstract: Pre-clinical studies indicate that neural stem cells (NSCs) can limit or reverse CNS damage through direct cell replacement, promotion of regeneration, or delivery of therapeutic agents. Immortalized NSC lines are in growing demand due to the inherent limitations of adult patient-derived NSCs, including availability, expandability, potential for genetic modifications, and costs. Here, we describe the generation and characterization of a new human fetal NSC line, immortalized by transduction with L-MYC (LM-NSC008) that in vitro displays both self-renewal and multipotent differentiation into neurons, oligodendrocytes, and astrocytes. These LM-NSC008 cells were non-tumorigenic in vivo, and migrated to orthotopic glioma xenografts in immunodeficient mice. When administered intranasally, LM-NSC008 distributed specifically to sites of traumatic brain injury (TBI). These data support the therapeutic development of immortalized LM-NSC008 cells for allogeneic use in TBI and other CNS diseases.
authors.affiliation: Department of Developmental and Stem Cell Biology, City of Hope National Medical Center and Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Zhongqi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Developmental and Stem Cell Biology, City of Hope National Medical Center and Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Oganesyan
authors.affiliation: Department of Developmental and Stem Cell Biology, City of Hope National Medical Center and Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Mooney
authors.affiliation: Department of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO 63110, USA.
authors.forename: Xianfang
authors.initials: X
authors.lastname: Rong
authors.affiliation: Department of Developmental and Stem Cell Biology, City of Hope National Medical Center and Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Christensen
authors.affiliation: Department of Developmental and Stem Cell Biology, City of Hope National Medical Center and Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: David
authors.initials: D
authors.lastname: Shahmanyan
authors.affiliation: Department of Epigenetics, Institute of Bioorganic Chemistry of the Polish Academy of Sciences, 61-704 Poznan, Poland.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Perrigue
authors.affiliation: Department of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO 63110, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Benetatos
authors.affiliation: Department of Developmental and Stem Cell Biology, City of Hope National Medical Center and Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Lusine
authors.initials: L
authors.lastname: Tsaturyan
authors.affiliation: Department of Developmental and Stem Cell Biology, City of Hope National Medical Center and Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Soraya
authors.initials: S
authors.lastname: Aramburo
authors.affiliation: Department of Developmental and Stem Cell Biology, City of Hope National Medical Center and Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Annala
authors.affiliation: Integrative Genomics Core, City of Hope National Medical Center and Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Immunology and Biotechnology, University of Pécs Medical School, Pécs 7624, Hungary.
authors.forename: Joseph
authors.initials: J
authors.lastname: Najbauer
authors.affiliation: Integrative Genomics Core, City of Hope National Medical Center and Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Developmental and Stem Cell Biology, City of Hope National Medical Center and Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Barish
authors.affiliation: Department of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO 63110, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Brody
authors.affiliation: Department of Developmental and Stem Cell Biology, City of Hope National Medical Center and Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Aboody
authors.affiliation: Department of Developmental and Stem Cell Biology, City of Hope National Medical Center and Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA. Electronic address: mgutova@coh.org.
authors.forename: Margarita
authors.initials: M
authors.lastname: Gutova
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D000066673:Cell Self Renewal / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D016259:Genes, myc; D055106:Genome-Wide Association Study; D064593:Heterografts; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D033581:Stem Cell Transplantation; D059467:Transcriptome; D014161:Transduction, Genetic; D019076:Transgenes