scholarly journals Potential of Neural Stem Cells for the Treatment of Brain Tumors

2008 ◽  
Vol 2 ◽  
pp. CMO.S747
Author(s):  
P. Taupin
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cellular Therapy ◽  
Neurological Diseases ◽  
Neural Progenitor ◽  
Multipotent Cells ◽  
The Brain ◽  
Combine Gene ◽  
Potential Use

Neural stem cells (NSCs) are self-renewing multipotent cells that generate the main phenotypes of the nervous system, neurons, astrocytes and oligodendrocytes. As such they hold the promise to treat a broad range of neurological diseases and injuries. Neural progenitor and stem cells have been isolated and characterized in vitro, from adult, fetal and post-mortem tissues, providing sources of material for cellular therapy. However, NSCs are still elusive cells and remain to be unequivocally identified and characterized, limiting their potential use for therapy. Neural progenitor and stem cells, isolated and cultured in vitro, can be genetically modified and when transplanted migrate to tumor sites in the brain. These intrinsic properties of neural progenitor and stem cells provide tremendous potential to bolster the translation of NSC research to therapy. It is proposed to combine gene therapy and cellular therapy to treat brain cancers. Hence, neural progenitor and stem cells provide new opportunities for the treatment of brain cancers.

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

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.

scholarly journals Fibronectin Promotes Survival and Migration of Primary Neural Stem Cells Transplanted into the Traumatically Injured Mouse Brain

2002 ◽  
Vol 11 (3) ◽  
pp. 283-295 ◽  
Author(s):  
Matthew C. Tate ◽  
Deborah A. Shear ◽  
Stuart W. Hoffman ◽  
Donald G. Stein ◽  
David R. Archer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cellular Therapy ◽  
Cell Types ◽  
Survival Times ◽  
Germinal Zone ◽  
Cortical Contusion ◽  
Multiple Cell ◽  
And Migration

Multipotential stem cells are an attractive choice for cell therapy after traumatic brain injury (TBI), as replacement of multiple cell types may be required for functional recovery. In the present study, neural stem cells (NSCs) derived from the germinal zone of E14.5 GFP-expressing mouse brains were cultured as neurospheres in FGF2-enhanced medium. When FGF2 was removed in vitro, NSCs expressed phenotypic markers for neurons, astrocytes, and oligodendrocytes and exhibited migratory behavior in the presence of adsorbed fibronectin (FN). NSCs (105 cells) were transplanted into mouse brains 1 week after a unilateral, controlled, cortical contusion (depth = 1 mm, velocity = 6 m/s, duration = 150 ms) (n = 19). NSCs were injected either directly into the injury cavity with or without an injectable FN-based scaffold [collagen I (CnI)/ FN gel; n = 14] or into the striatum below the injury cavity (n = 5). At all time points examined (1 week to 3 months posttransplant), GFP+ cells were confined to the ipsilateral host brain tissue. At 1 week, cells injected into the injury cavity lined the injury penumbra while cells inserted directly into the striatum remained in or around the needle track. Striatal transplants had a lower number of surviving GFP+ cells relative to cavity injections at the 1 week time point (p < 0.01). At the longer survival times (3 weeks–3 months), 63–76% of transplanted cells migrated into the fimbria hippocampus regardless of injection site, perhaps due to cues from the degenerating hippocampus. Furthermore, cells injected into the cavity within a FN-containing matrix showed increased survival and migration at 3 weeks (p < 0.05 for both) relative to injections of cells alone. These results suggest that FGF2-responsive NSCs present a promising approach for cellular therapy following trauma and that the transplant location and environment may play an important role in graft survival and integration.

scholarly journals Spinal cord neural stem cells heterogeneity in postnatal development

STEMedicine ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. e19
Author(s):  
Jelena Ban ◽  
Miranda Mladinic
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Types ◽  
In Vitro Models ◽  
Cell Potential ◽  
Neurogenic Niche ◽  
The Brain

Neural stem cells are capable of generating new neurons during development as well as in the adulthood and represent one of the most promising tools to replace lost or damaged neurons after injury or neurodegenerative disease. Unlike the brain, neurogenesis in the adult spinal cord is poorly explored and the comprehensive characterization of the cells that constitute stem cell neurogenic niche is still missing. Moreover, the terminology used to specify developmental and/or anatomical CNS regions, where neurogenesis in the spinal cord occurs, is not consensual and the analogy with the brain is often unclear. In this review, we will try to describe the heterogeneity of the stem cell types in the spinal cord ependymal zone, based on their origin and stem cell potential. We will also consider specific animal in vitro models that could be useful to identify “the right” stem cell candidate for cell replacement therapies.   

scholarly journals In Vitro Studies on Therapeutic Effects of Cannabidiol in Neural Cells: Neurons, Glia, and Neural Stem Cells

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 6077
Author(s):  
Jungnam Kim ◽  
Hyunwoo Choi ◽  
Eunhye K. Kang ◽  
Gil Yong Ji ◽  
Youjeong Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Culture ◽  
Neural Stem Cells ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
In Vitro Studies ◽  
Therapeutic Effects ◽  
Neural Cells ◽  
Prevention And Treatment

(‒)-Cannabidiol (CBD) is one of the major phytocannabinoids extracted from the Cannabis genus. Its non-psychoactiveness and therapeutic potential, partly along with some anecdotal—if not scientific or clinical—evidence on the prevention and treatment of neurological diseases, have led researchers to investigate the biochemical actions of CBD on neural cells. This review summarizes the previously reported mechanistic studies of the CBD actions on primary neural cells at the in vitro cell-culture level. The neural cells are classified into neurons, microglia, astrocytes, oligodendrocytes, and neural stem cells, and the CBD effects on each cell type are described. After brief introduction on CBD and in vitro studies of CBD actions on neural cells, the neuroprotective capability of CBD on primary neurons with the suggested operating actions is discussed, followed by the reported CBD actions on glia and the CBD-induced regeneration from neural stem cells. A summary section gives a general overview of the biochemical actions of CBD on neural cells, with a future perspective. This review will provide a basic and fundamental, but crucial, insight on the mechanistic understanding of CBD actions on neural cells in the brain, at the molecular level, and the therapeutic potential of CBD in the prevention and treatment of neurological diseases, although to date, there seem to have been relatively limited research activities and reports on the cell culture-level, in vitro studies of CBD effects on primary neural cells.

scholarly journals Neuroprotective properties of the C-Jun N-terminal kinase (JNK) inhibitor in hypoxic hypoxia

2019 ◽  
Vol 18 (2) ◽  
pp. 80-88
Author(s):  
G. N. Zyuz’kov ◽  
E. V. Udut ◽  
L. A. Miroshnichenko ◽  
T. Ju. Poljakova ◽  
E. V. Simanina ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Nerve Tissue ◽  
Hypoxic Exposure ◽  
Experimental Animals ◽  
Neuronal Stem Cells ◽  
Orientation And Exploratory Behavior ◽  
The Brain

The aim of the study was to reveal the influence of the JNK inhibitor on the induction of disturbances in the psychoneurological status of experimental animals in the modeling of posthypoxic encephalopathy and to reveal the mechanisms of its action related to the functioning of the neural stem cells of the brain. Materials and methods. The experiments were performed on 64 male outbred mice. Posthypoxic encephalopathy was modeled in non-native mice with hypoxia of the hermetic volume. The JNK inhibitor was administered to mice subcutaneously at a dose of 15 mg/kg once before hypoxic exposure. We studied the neuropsychiatric status, the content of neuronal stem cells in the subventricular zone of the brain of experimental animals, and the direct effect of the JNK inhibitor on intact neural stem cells in vitro. Results. The expressed cerebroprotective action of the pharmacological agent was revealed, which consisted of normalizing the indices of orientation and exploratory behavior and conditioned activity in experimental animals. These effects developed against a background of a significant increase in the content of neural stem cells in the subventricular zone of the brain. In the experiments in vitro, a direct stimulating effect of the JNK inhibitor on neural stem cells was found. Conclusions. The obtained results showed a neuroprotective action of the JNK inhibitor. At the same time, the prevention and compensation of the development of disturbances in the activity of the central nervous system is based on the preservation of the ability of the nerve tissue to repair andassociated with the functioning of resident neural stem cells.

Abstract PO-017: Radiotherapy in combination with the brain penetrant ATM inhibitor AZD1390 does not exacerbate radiation toxicity of neural stem cells in vitro or in vivo

2021 ◽  
Author(s):  
Rodrigo Guttierez-Quintana ◽  
David J. Walker ◽  
Mark R. Jackson ◽  
Natividad Gomez-Roman ◽  
Sandeep Chahal ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Radiation Toxicity ◽  
The Brain

scholarly journals Response of neural stem cells to ionizing radiation

2019 ◽  
Vol 15 (4) ◽  
pp. 157-160
Author(s):  
Katarzyna Ida Kulcenty ◽  
Joanna Patrycja Wróblewska ◽  
Wiktoria Maria Suchorska
Keyword(s):  
Stem Cells ◽  
Ionizing Radiation ◽  
Neural Stem Cells ◽  
Current Knowledge ◽  
Critical Role ◽  
Brain Regions ◽  
Cancer Therapies ◽  
Multipotent Cells ◽  
Radiation Induced ◽  
The Brain

Adult neurons are believed to be in a state of growth arrest. The generation of neurons is complete at the time of birth in most of the brain regions. However neurogenesis is present through life in the dentate gyrus of hippocampus and the lateral ventricles due to the presence of neural stem cells (NSC). This postnatal neurogenesis in hippocampus plays a critical role in cognitive development mainly in learning and memory functions. NSC are self-renewing, multipotent cells that generate the neurons and glia of the nervous system. Due to their high proliferation, NSC are highly sensitive to ionizing radiation. This review describes the current knowledge on impact of ionizing radiation on neural stem cells biology. Widening the knowledge of mechanisms involved in radiation-induced neurotoxicity at the level of NSC may help to overcome in the future the side effects occurring after anti-cancer therapies of the brain and help to protect and maintain neurogenesis.

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