title: Derivation of neural stem cells from human adult peripheral CD34+ cells for an autologous model of neuroinflammation.
abstract: Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine.
authors.affiliation: Translational Neuroscience Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Tongguang
authors.initials: T
authors.lastname: Wang
authors.forename: Elliot
authors.initials: E
authors.lastname: Choi
authors.forename: Maria Chiara G
authors.initials: MC
authors.lastname: Monaco
authors.forename: Emilie
authors.initials: E
authors.lastname: Campanac
authors.forename: Marie
authors.initials: M
authors.lastname: Medynets
authors.forename: Thao
authors.initials: T
authors.lastname: Do
authors.forename: Prashant
authors.initials: P
authors.lastname: Rao
authors.forename: Kory R
authors.initials: KR
authors.lastname: Johnson
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Elkahloun
authors.forename: Gloria
authors.initials: G
authors.lastname: Von Geldern
authors.forename: Tory
authors.initials: T
authors.lastname: Johnson
authors.forename: Sriram
authors.initials: S
authors.lastname: Subramaniam
authors.forename: Dax A
authors.initials: DA
authors.lastname: Hoffman
authors.forename: Dax
authors.initials: D
authors.lastname: Hoffman
authors.forename: Eugene
authors.initials: E
authors.lastname: Major
authors.forename: Avindra
authors.initials: A
authors.lastname: Nath
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D016000:Cluster Analysis; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D000090062:Kruppel-Like Factor 4; D008213:Lymphocyte Activation / Q000276:immunology; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018952:Antigens, CD34; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4