Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat

10.1038/nn974 ◽  
2002 ◽  
Vol 5 (12) ◽  
pp. 1271-1278 ◽  
Author(s):  
Ping Wu ◽  
Yevgeniya I. Tarasenko ◽  
Yanping Gu ◽  
Li-Yen M. Huang ◽  
Richard E. Coggeshall ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cholinergic Neurons ◽  
Human Neural Stem Cells ◽  
Adult Rat

Human Neural Stem Cells Genetically Modified to Express Human Nerve Growth Factor (NGF) Gene Restore Cognition in the Mouse with Ibotenic Acid-Induced Cognitive Dysfunction

2012 ◽  
Vol 21 (11) ◽  
pp. 2487-2496 ◽  
Author(s):  
Hong J. Lee ◽  
In J. Lim ◽  
Seung W. Park ◽  
Yun B. Kim ◽  
Yong Ko ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nerve Growth Factor ◽  
Cognitive Function ◽  
Growth Factor ◽  
Neural Stem Cells ◽  
Cholinergic Neurons ◽  
Ibotenic Acid ◽  
Learning Deficit ◽  
Human Neural Stem Cells ◽  
The Brain

Alzheimer's disease (AD) is characterized by degeneration and loss of neurons and synapses throughout the brain, causing the progressive decline in cognitive function leading to dementia. No effective treatment is currently available. Nerve growth factor (NGF) therapy has been proposed as a potential treatment of preventing degeneration of basal forebrain cholinergic neurons in AD. In a previous study, AD patient's own fibroblasts genetically modified to produce NGF were transplanted directly into the brain and protected cholinergic neurons from degeneration and improved cognitive function in AD patients. In the present study, human neural stem cells (NSCs) are used in place of fibroblasts to deliver NGF in ibotenic acid-induced learning-deficit rats. Intrahippocampal injection of ibotenic acid caused severe neuronal loss, resulting in learning and memory deficit. NGF protein released by F3.NGF human NSCs in culture medium is 10-fold over the control F3 naive NSCs at 1.2 μg/106 cells/day. Overexpression of NGF in F3.NGF cells induced improved survival of NSCs from cytotoxic agents H2O2, Aβ, or ibotenic acid in vitro. Intrahippocampal transplantation of F3.NGF cells was found to express NGF and fully improved the learning and memory function of ibotenic acid-challenged animals. Transplanted F3.NGF cells were found all over the brain and differentiated into neurons and astrocytes. The present study demonstrates that human NSCs overexpressing NGF improve cognitive function of learning-deficit model mice.

Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia

2004 ◽  
Vol 1016 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Kon Chu ◽  
Manho Kim ◽  
Kyung-Il Park ◽  
Sang-Wuk Jeong ◽  
Hee-Kwon Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Rat Brain ◽  
Focal Ischemia ◽  
Human Neural Stem Cells ◽  
Adult Rat ◽  
Sensorimotor Deficits ◽  
Adult Rat Brain

scholarly journals mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1043 ◽  
Author(s):  
Phil Jun Kang ◽  
Daryeon Son ◽  
Tae Hee Ko ◽  
Wonjun Hong ◽  
Wonjin Yun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Human Urine ◽  
Neurological Disorders ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Global Gene Expression ◽  
Patient Specific ◽  
Human Neural Stem Cells

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, efficient, and patient-specific manner.

scholarly journals BCOR Internal Tandem Duplication Expression in Neural Stem Cells Promotes Growth, Invasion, and Expression of PRC2 Targets

2021 ◽  
Vol 22 (8) ◽  
pp. 3913
Author(s):  
Satoshi Nakata ◽  
Ming Yuan ◽  
Jeffrey A. Rubens ◽  
Ulf D. Kahlert ◽  
Jarek Maciaczyk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Tandem Duplication ◽  
Target Genes ◽  
Cellular Growth ◽  
Central Nervous System Tumor ◽  
Internal Tandem Duplication ◽  
Invasion And Migration ◽  
Human Neural Stem Cells ◽  
And Migration

Central nervous system tumor with BCL6-corepressor internal tandem duplication (CNS-BCOR ITD) is a malignant entity characterized by recurrent alterations in exon 15 encoding the essential binding domain for the polycomb repressive complex (PRC). In contrast to deletion or truncating mutations seen in other tumors, BCOR expression is upregulated in CNS-BCOR ITD, and a distinct oncogenic mechanism has been suggested. However, the effects of this change on the biology of neuroepithelial cells is poorly understood. In this study, we introduced either wildtype BCOR or BCOR-ITD into human and murine neural stem cells and analyzed them with quantitative RT-PCR and RNA-sequencing, as well as growth, clonogenicity, and invasion assays. In human cells, BCOR-ITD promoted derepression of PRC2-target genes compared to wildtype BCOR. A similar effect was found in clinical specimens from previous studies. However, no growth advantage was seen in the human neural stem cells expressing BCOR-ITD, and long-term models could not be established. In the murine cells, both wildtype BCOR and BCOR-ITD overexpression affected cellular differentiation and histone methylation, but only BCOR-ITD increased cellular growth, invasion, and migration. BCOR-ITD overexpression drives transcriptional changes, possibly due to altered PRC function, and contributes to the oncogenic transformation of neural precursors.

scholarly journals Immunosuppressants Affect Human Neural Stem Cells In Vitro but Not in an In Vivo Model of Spinal Cord Injury

2013 ◽  
Vol 2 (10) ◽  
pp. 731-744 ◽  
Author(s):  
Christopher J. Sontag ◽  
Hal X. Nguyen ◽  
Noriko Kamei ◽  
Nobuko Uchida ◽  
Aileen J. Anderson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
In Vivo Model ◽  
Human Neural Stem Cells ◽  
Cord Injury

scholarly journals Human Neural Stem Cells Induce Functional Myelination in Mice with Severe Dysmyelination

2012 ◽  
Vol 4 (155) ◽  
pp. 155ra136-155ra136 ◽  
Author(s):  
N. Uchida ◽  
K. Chen ◽  
M. Dohse ◽  
K. D. Hansen ◽  
J. Dean ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Human Neural Stem Cells

scholarly journals Robust Generation of Oligodendrocyte Progenitors from Human Neural Stem Cells and Engraftment in Experimental Demyelination Models in Mice

PLoS ONE ◽  
2010 ◽  
Vol 5 (4) ◽  
pp. e10145 ◽  
Author(s):  
Margherita Neri ◽  
Claudio Maderna ◽  
Daniela Ferrari ◽  
Chiara Cavazzin ◽  
Angelo L. Vescovi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Oligodendrocyte Progenitors ◽  
Human Neural Stem Cells ◽  
Experimental Demyelination
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