A profusion of neural stem cells in the brain of the spiny mouse, Acomys cahirinus

Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). NSCs are the multipotent progenitor cells of the brain that have the ability to form neurons, astrocytes, and oligodendrocytes. Viral infections often alter the function of NSCs, with profound impacts on the growth and repair of the brain. There are a wide spectrum of effects on NSCs, which differ by the type of virus, the model system, the cell types studied, and the age of the host. Thus, it is a challenge to predict and define the consequences of interactions between viruses and NSCs. The purpose of this review is to dissect the mechanisms by which viruses can affect survival, proliferation, and differentiation of NSCs. This review also sheds light on the contribution of key antiviral cytokines in the impairment of NSC activity during a viral infection, revealing a complex interplay between NSCs, viruses, and the immune system.

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P50. Role of glioma produced CM1 in the brain tumor tropism of human neural stem cells

Differentiation ◽

10.1016/j.diff.2010.09.056 ◽

2010 ◽

Vol 80 ◽

pp. S33-S34

Author(s):

J. Jeon ◽

S. Cho ◽

K. Cho ◽

Y. Lee ◽

M. Lee

Keyword(s):

Stem Cells ◽

Brain Tumor ◽

Neural Stem Cells ◽

Human Neural Stem Cells ◽

Tumor Tropism ◽

The Brain

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SCIDOT-22. INTRACEREBROVENTRICULAR DELIVERY OF TUMOR-HOMING CYTOTOXIC HUMAN INDUCED NEURAL STEM CELLS FOR TREATMENT OF BRAIN METASTASES

Neuro-Oncology ◽

10.1093/neuonc/noz175.1158 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi276-vi276

Author(s):

Wulin Jiang ◽

Alison Mercer-Smith ◽

Juli Bago ◽

Simon Khagi ◽

Carey Anders ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Brain Metastases ◽

Neural Stem Cells ◽

Tumor Homing ◽

Migration Assays ◽

Induced Neural Stem Cells ◽

First Time ◽

The Brain

Abstract INTRODUCTION Non-small cell lung cancer (NSCLC) and breast cancer are the most common cancers that metastasize to the brain. New therapies are needed to target and eradicate metastases. We have developed genetically-engineered induced neural stem cells (hiNSCs) derived from human fibroblasts that selectively home to tumors and release the cytotoxic protein TRAIL. Building on these results, we explored the efficacy of hiNSC therapy delivered via intracerebroventricular (ICV) injections for the treatment of metastatic foci in the brain for the first time. METHODS We performed in vitro efficacy and migration assays in conjunction with in vivo studies to determine the migration, persistence, and efficacy of therapeutic hiNSCs against H460 NSCLC and triple-negative breast cancer MB231-Br tumors in the brain. Following the establishment of tumors in the brains of nude mice, hiNSCs were injected directly into the tumor or the ventricle contralateral to the tumor. The migration and persistence of hiNSCs were investigated by following the bioluminescence of the hiNSCs. The therapeutic efficacy of the hiNSCs was determined by following the bioluminescence of the tumor. RESULTS/ CONCLUSION Co-culture results demonstrated that hiNSC therapy reduced the viability of H460 and MB231-Br up to 75% and 99.8% respectively compared to non-treated controls. In vitro migration assays showed significant directional migration toward both lung and breast cancer cells within 4 days. ICV-administered hiNSC serial imaging shows that cells persisted for >1 week in the brain. Fluorescent analysis of tissue sections showed that hiNSCs co-localized with lateral and contralateral tumors within 7 days. Using H460 and MB231-Br models, kinetic tracking of intracranial tumor volumes showed intratumoral or ICV-injected therapeutic hiNSCs suppressed the growth rate of brain tumors by 31-fold and 3-fold, respectively. This work demonstrates for the first time that we can effectively deliver personalized cytotoxic tumor-homing cells through the ventricles to target brain metastases.

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Dynamic Modelling of Interactions between Microglia and Endogenous Neural Stem Cells in the Brain during a Stroke

Mathematics ◽

10.3390/math8010132 ◽

2020 ◽

Vol 8 (1) ◽

pp. 132 ◽

Cited By ~ 1

Author(s):

Awatif Jahman Alqarni ◽

Azmin Sham Rambely ◽

Ishak Hashim

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Dynamic Modelling ◽

Dynamic Effect ◽

Brain Cells ◽

Activated Microglia ◽

Model Studies ◽

The Impact ◽

The Brain ◽

Endogenous Neural Stem Cells

In this paper, we study the interactions between microglia and neural stem cells and the impact of these interactions on the brain cells during a stroke. Microglia cells, neural stem cells, the damage on brain cells from the stroke and the impacts these interactions have on living brain cells are considered in the design of mathematical models. The models consist of ordinary differential equations describing the effects of microglia on brain cells and the interactions between microglia and neural stem cells in the case of a stroke. Variables considered include: resident microglia, classically activated microglia, alternatively activated microglia, neural stem cells, tissue damage on cells in the brain, and the impacts these interactions have on living brain cells. The first model describes what happens in the brain at the stroke onset during the first three days without the generation of any neural stem cells. The second model studies the dynamic effect of microglia and neural stem cells on the brain cells following the generation of neural stem cells and potential recovery after this stage. We look at the stability and the instability of the models which are both studied analytically. The results show that the immune cells can help the brain by cleaning dead cells and stimulating the generation of neural stem cells; however, excessive activation may cause damage and affect the injured region. Microglia have beneficial and harmful functions after ischemic stroke. The microglia stimulate neural stem cells to generate new cells that substitute dead cells during the recovery stage but sometimes the endogenous neural stem cells are highly sensitive to inflammatory in the brain.

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Comparison of the Behavior of Neural Stem Cells in the Brain of Normal and twitcher Mice after Neonatal Transplantation

Stem Cells and Development ◽

10.1089/scd.2006.0092 ◽

2007 ◽

Vol 16 (3) ◽

pp. 429-438 ◽

Cited By ~ 9

Author(s):

Guoying Zhao ◽

Nigel F. McCarthy ◽

Paul A. Sheehy ◽

Rosanne M. Taylor

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

The Brain

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Stereological Analysis on Migration of Human Neural Stem Cells in the Brain of Rats Bearing Glioma

Neurosurgery ◽

10.1227/01.neu.0000363720.07070.a8 ◽

2010 ◽

Vol 66 (2) ◽

pp. 333-342 ◽

Cited By ~ 22

Author(s):

Jae-Ho Kim ◽

Jong-Eun Lee ◽

Seung U. Kim ◽

Kyung-Gi Cho

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Stereological Analysis ◽

Human Neural Stem Cells ◽

The Brain

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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

Cell Transplantation ◽

10.3727/096368912x638964 ◽

2012 ◽

Vol 21 (11) ◽

pp. 2487-2496 ◽

Cited By ~ 53

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.

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