scholarly journals PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Shunlei Duan ◽  
Guohong Yuan ◽  
Xiaomeng Liu ◽  
Ruotong Ren ◽  
Jingyi Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Human Neural Stem Cells ◽  
Glioblastoma Stem Cell

scholarly journals Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2)

2020 ◽  
Vol 91 (4) ◽  
pp. 396-401 ◽  
Author(s):  
Keith W Muir ◽  
Diederik Bulters ◽  
Mark Willmot ◽  
Nikola Sprigg ◽  
Anand Dixit ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Multicentre Study ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Upper Limb ◽  
Limb Movement ◽  
Human Neural Stem Cells ◽  
Human Neural Stem Cell ◽  
Cell Implantation

BackgroundHuman neural stem cell implantation may offer improved recovery from stroke. We investigated the feasibility of intracerebral implantation of the allogeneic human neural stem cell line CTX0E03 in the subacute—chronic recovery phase of stroke and potential measures of therapeutic response in a multicentre study.MethodsWe undertook a prospective, multicentre, single-arm, open-label study in adults aged >40 years with significant upper limb motor deficits 2–13 months after ischaemic stroke. 20 million cells were implanted by stereotaxic injection to the putamen ipsilateral to the cerebral infarct. The primary outcome was improvement by 2 or more points on the Action Research Arm Test (ARAT) subtest 2 at 3 months after implantation.FindingsTwenty-three patients underwent cell implantation at eight UK hospitals a median of 7 months after stroke. One of 23 participants improved by the prespecified ARAT subtest level at 3 months, and three participants at 6 and 12 months. Improvement in ARAT was seen only in those with residual upper limb movement at baseline. Transient procedural adverse effects were seen, but no cell-related adverse events occurred up to 12 months of follow-up. Two deaths were unrelated to trial procedures.InterpretationAdministration of human neural stem cells by intracerebral implantation is feasible in a multicentre study. Improvements in upper limb function occurred at 3, 6 and 12 months, but not in those with absent upper limb movement at baseline, suggesting a possible target population for future controlled trials.FundingReNeuron, Innovate UK (application no 32074-222145).Trial registration numberEudraCT Number: 2012-003482-18

scholarly journals Stem Cell Bioprinting: Functional 3D Neural Mini-Tissues from Printed Gel-Based Bioink and Human Neural Stem Cells (Adv. Healthcare Mater. 12/2016)

2016 ◽  
Vol 5 (12) ◽  
pp. 1428-1428 ◽  
Author(s):  
Qi Gu ◽  
Eva Tomaskovic-Crook ◽  
Rodrigo Lozano ◽  
Yu Chen ◽  
Robert M. Kapsa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Human Neural Stem Cells

Electroconductive nanoscale topography for enhanced neuronal differentiation and electrophysiological maturation of human neural stem cells

Nanoscale ◽  
2017 ◽  
Vol 9 (47) ◽  
pp. 18737-18752 ◽  
Author(s):  
Kisuk Yang ◽  
Seung Jung Yu ◽  
Jong Seung Lee ◽  
Hak-Rae Lee ◽  
Gyeong-Eon Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neuronal Differentiation ◽  
Neural Stem Cell ◽  
Human Neural Stem Cells ◽  
Nanoscale Topography

Electroconductive nanotopography for enhanced neurogenesis of neural stem cell.

The effect of hypoxia and laminin-rich substrates on the proliferative behavior of human neural stem cells

2016 ◽  
Vol 4 (20) ◽  
pp. 3509-3514 ◽  
Author(s):  
Sasan Sharee Ghourichaee ◽  
Jennie B. Leach
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Density ◽  
Proliferating Cells ◽  
Human Neural Stem Cells ◽  
Cells Cultured

Human neural stem cells cultured on laminin and Matrigel under hypoxia significantly increase both the stem cell density and the percentage of activity proliferating cells.

scholarly journals UTX/KDM6A suppresses AP-1 and a gliogenesis program during neural differentiation of human pluripotent stem cells

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Beisi Xu ◽  
Brett Mulvey ◽  
Muneeb Salie ◽  
Xiaoyang Yang ◽  
Yurika Matsui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Regulation ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Gene Activation ◽  
Histone H3 ◽  
Chromatin Accessibility ◽  
Open Chromatin ◽  
Human Neural Stem Cells

Abstract Background UTX/KDM6A is known to interact and influence multiple different chromatin modifiers to promote an open chromatin environment to facilitate gene activation, but its molecular activities in developmental gene regulation remain unclear. Results We report that in human neural stem cells, UTX binding correlates with both promotion and suppression of gene expression. These activities enable UTX to modulate neural stem cell self-renewal, promote neurogenesis, and suppress gliogenesis. In neural stem cells, UTX has a less influence over histone H3 lysine 27 and lysine 4 methylation but more predominantly affects histone H3 lysine 27 acetylation and chromatin accessibility. Furthermore, UTX suppresses components of AP-1 and, in turn, a gliogenesis program. Conclusions Our findings revealed that UTX coordinates dualistic gene regulation to govern neural stem cell properties and neurogenesis–gliogenesis switch.

scholarly journals Intranasal Transplantation of Human Neural Stem Cells Ameliorates Alzheimer's Disease-Like Pathology in a Mouse Model

2021 ◽  
Vol 13 ◽  
Author(s):  
Mei-Hong Lu ◽  
Wen-Li Ji ◽  
Hong Chen ◽  
Yan-Yun Sun ◽  
Xiu-Yun Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transgenic Mice ◽  
Neural Stem Cells ◽  
Neurological Disorders ◽  
Human Neural Stem Cells ◽  
Degrading Enzymes ◽  
Cholinergic Dysfunction ◽  
Β Amyloid ◽  
Delivery Approach

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairments, which has no effective therapy. Stem cell transplantation shows great potential in the therapy of various disease. However, the application of stem cell therapy in neurological disorders, especially the ones with a long-term disease course such as AD, is limited by the delivery approach due to the presence of the brain blood barrier. So far, the most commonly used delivery approach in the therapy of neurological disorders with stem cells in preclinical and clinical studies are intracranial injection and intrathecal injection, both of which are invasive. In the present study, we use repetitive intranasal delivery of human neural stem cells (hNSCs) to the brains of APP/PS1 transgenic mice to investigate the effect of hNSCs on the pathology of AD. The results indicate that the intranasally transplanted hNSCs survive and exhibit extensive migration and higher neuronal differentiation, with a relatively limited glial differentiation. A proportion of intranasally transplanted hNSCs differentiate to cholinergic neurons, which rescue cholinergic dysfunction in APP/PS1 mice. In addition, intranasal transplantation of hNSCs attenuates β-amyloid accumulation by upregulating the expression of β-amyloid degrading enzymes, insulin-degrading enzymes, and neprilysin. Moreover, intranasal transplantation of hNSCs ameliorates other AD-like pathology including neuroinflammation, cholinergic dysfunction, and pericytic and synaptic loss, while enhancing adult hippocampal neurogenesis, eventually rescuing the cognitive deficits of APP/PS1 transgenic mice. Thus, our findings highlight that intranasal transplantation of hNSCs benefits cognition through multiple mechanisms, and exhibit the great potential of intranasal administration of stem cells as a non-invasive therapeutic strategy for AD.

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.

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