title: Direct induction of human neural stem cells from peripheral blood hematopoietic progenitor cells.
abstract: Human disease specific neuronal cultures are essential for generating in vitro models for human neurological diseases. However, the lack of access to primary human adult neural cultures raises unique challenges. Recent developments in induced pluripotent stem cells (iPSC) provides an alternative approach to derive neural cultures from skin fibroblasts through patient specific iPSC, but this process is labor intensive, requires special expertise and large amounts of resources, and can take several months. This prevents the wide application of this technology to the study of neurological diseases. To overcome some of these issues, we have developed a method to derive neural stem cells directly from human adult peripheral blood, bypassing the iPSC derivation process. Hematopoietic progenitor cells enriched from human adult peripheral blood were cultured in vitro and transfected with Sendai virus vectors containing transcriptional factors Sox2, Oct3/4, Klf4, and c-Myc. The transfection results in morphological changes in the cells which are further selected by using human neural progenitor medium containing basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). The resulting cells are characterized by the expression for neural stem cell markers, such as nestin and SOX2. These neural stem cells could be further differentiated to neurons, astroglia and oligodendrocytes in specified differentiation media. Using easily accessible human peripheral blood samples, this method could be used to derive neural stem cells for further differentiation to neural cells for in vitro modeling of neurological disorders and may advance studies related to the pathogenesis and treatment of those diseases.
authors: Translational Neuroscience Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health; david.wang@nih.gov.
authors: Tongguang
authors: T
authors: Wang
authors: Translational Neuroscience Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health.
authors: Elliot
authors: E
authors: Choi
authors: Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health.
authors: Maria Chiara G
authors: MC
authors: Monaco
authors: Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health.
authors: Eugene O
authors: EO
authors: Major
authors: Translational Neuroscience Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health.
authors: Marie
authors: M
authors: Medynets
authors: Translational Neuroscience Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health.
authors: Avindra
authors: A
authors: Nath
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000097:blood; D001253:Astrocytes / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology; D003470:Culture Media; D016222:Fibroblast Growth Factor 2; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D064231:Nestin / Q000096:biosynthesis; D058953:Neural Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology; D009836:Oligodendroglia / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A
chemical_list: D018952:Antigens, CD34; D003470:Culture Media; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D064231:Nestin; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2
references: PLoS Curr. 2010 Oct 28;2:RRN1193
references: 21037797
references: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14926-31
references: 14634211
references: Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14234-9
references: 21821793
references: PLoS One. 2013 Nov 26;8(11):e81720
references: 24303066
references: Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2527-32
references: 22308465
references: Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10343-8
references: 21646515
references: Cell. 2006 Aug 25;126(4):663-76
references: 16904174
references: Cell Stem Cell. 2012 Apr 6;10(4):473-9
references: 22445518
references: Nature. 2010 Feb 25;463(7284):1035-41
references: 20107439
references: PLoS One. 2011;6(6):e20941
references: 21687800
references: J Vis Exp. 2012 Apr 22;(62):null
references: 22546813
references: PLoS One. 2011;6(7):e21801
references: 21765916
references: Cell. 2007 Nov 30;131(5):861-72
references: 18035408
references: Stem Cell Res. 2012 Mar;8(2):259-73
references: 22265745
references: Gene Ther. 2003 Feb;10(3):272-7
references: 12571635
references: Cell. 2008 Sep 5;134(5):877-86
references: 18691744