Paracrine Neuroprotective Effects of Neural Stem Cells on Glutamate-Induced Cortical Neuronal Cell Excitotoxicity

Geranmayeh, Mohammad Hossein; Baghbanzadeh, Ali; Barin, Abbas; Salar-Amoli, Jamileh; Dehghan, Mohammad Mehdi; Rahbarghazi‬, Reza; Azari, Hassan

doi:10.15171/apb.2015.070

Cited by 14 publications

(10 citation statements)

References 37 publications

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“…Yet, other studies performed in vitro have shown that NSCs were able to elicit neuroprotective effects on neurons that were exposed to glutamate excitotoxicity and decreases the rate at which cell death occurred. 22 NSCs implanted onto spinal cord sections resulted in axonal growth from motor neurons toward stem cells via neurotrophic secretions like glial cell-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). 23 In addition, adipose-derived mesenchymal stem cells were able to rescue neurons from early death due to glutamate excitotoxicity by secreting various neurotrophins (NTs), including VEGF, hepatocyte growth factor, BDNF, and NGF.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia

et al. 2017

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The use of regenerative medicine to treat nervous system disorders like ataxia has been proposed to either replace or support degenerating neurons. In this study, we assessed the ability of human neural progenitor cells (hNPCs) to repair and restore the function of dying neurons within the spastic Han-Wistar rat (sHW), a model of ataxia. The sHW rat suffers from neurodegeneration of specific neurons, including cerebellar Purkinje cells and hippocampal CA3 pyramidal cells leading to the observed symptoms of forelimb tremor, hind-leg rigidity, gait abnormality, motor incoordination, and a shortened life span. To alleviate the symptoms of neurodegeneration and to replace or augment dying neurons, neuronal human progenitor cells were implanted into the sHW rats. At 30 d of age, male sHW mutant rats underwent subcutaneous implantation of an Alzet osmotic pump that infused cyclosporine (15 mg/kg/d) used to suppress the rat’s immune system. At 40 d, sHW rats received bilateral injections (500,000 cells in 5 µL media) of live hNPCs, dead hNPCs, live human embryonic kidney cells, or growth media either into the cerebellar cortex or into the hippocampus. To monitor results, motor activity scores (open-field testing) and weights of the animals were recorded weekly. The sHW rats that received hNPC transplantation into the cerebellum, at 60 d of age, displayed significantly higher motor activity scores and sustained greater weights and longevities than control-treated sHW rats or any hippocampal treatment group. In addition, cerebellar histology revealed that the transplanted hNPCs displayed signs of migration and signs of neuronal development in the degenerated Purkinje cell layer. This study revealed that implanted human progenitor cells reduced the ataxic symptoms in the sHW rat, identifying a future clinical use of these progenitor cells against ataxia and associated neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia

et al. 2017

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“…Cell viability assay was estimated using the 3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay [34]. …”

Section: Methodsmentioning

confidence: 99%

Lanthanum Chloride Inhibits LPS Mediated Expressions of Pro-Inflammatory Cytokines and Adhesion Molecules in HUVECs: Involvement of NF-κB-Jmjd3 Signaling

Chen

Xiao

Xing

et al. 2017

Cell Physiol Biochem

4,206

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Background/Aims: To investigate the regulation of LaCl₃ on lipopolysaccharides (LPS)-induced pro-inflammatory cytokines and adhesion molecules in human umbilical vein endothelial cells (HUVECs). Methods: Primary cultured HUVECs were pretreated with 2.5 µM LaCl₃ for 30 min followed by 1 µg/ml LPS for 2 h. Pro-inflammatory cytokine and adhesion molecule expressions were determined by real-time RT-PCR and ELISA. NF-κB/p65 nuclear translocation was examined by immunofluorescence and immuno-blot, and its DNA-binding activity was measured by chemiluminescence. Recruitment of NF-κB/p65, Jmjd3, and H3K27me3 to gene promoter regions was determined by ChIP-qPCR. Results: LaCl₃ exhibited no cytotoxic effects to primary HUVECs at concentrations ≤ 50 µM. LPS-mediated TNF-α, IL-1β, IL-6, MMP-9, and ICAM-1 production, nuclear translocation, and DNA-binding activity of NF-κB/p65, as well as Jmjd3 expression, were all reduced significantly by LaCl₃. Furthermore, LaCl₃ treatment significantly impaired LPS-induced enrichment of NF-κB/p65 to the promoter regions of TNF-α, MMP-9, IL-1β, ICAM-1, and IL-6; and of Jmjd3 to the promoter regions of TNF-α, MMP-9, IL-1β, and IL-6. H3K27me3 abundance in the promoter regions of TNF-α and ICAM-1 increased significantly in following LaCl₃ treatment. Conclusion: LaCl₃ inhibits pro-inflammatory cytokine and adhesion molecule expressions induced by LPS in HUVECs. NF-κB and histone demethylase Jmjd3 are involved in this effect.

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“…Obviously, the detected influence of conditioned media from 24-h cultures of rat FBNCs (E14-16), most of which are NSCs/NPCs, on the endogenous regeneration in the culture of neural cells of rat fetal brain with a mechanical model of neurotrauma in vitro is based on the cumulative effect of biologically active paracrine mediators (signaling molecules of secretome) produced by these cells in the culture medium [11,20,22,[37][38][39][40]. Secreted mediators are responsible for one of the main mechanisms of NSCs/NPCs effects, which means modulation of the local microenvironment around the affected area and activation of key inflammatory and regenerative programs in the CNS [11,14,21], i.e.…”

Section: Morphometric Study Of Morphological Changes In Neural Cell Culture With a Mechanical Model Of Neurotrauma Under Different Cultivmentioning

confidence: 99%

“…[10][11][12][13][14][15][16][17][18][19]. These secreted factors or NSCs/NPCs secretome [11,20] are the mediators of bystander-effects, able to regulate a wide range of processes at the cellular, tissue, organ and systemic levels and are considered a key component of these regulatory mechanisms [12,[21][22][23]. Given the limited clinical use of cell therapy in the TBI treatment at this stage, it seems promising to study the effectiveness of regenerative effects of NSCs/NPCs conditioned media as a source of their secretome and a possible alternative to direct cell transplantation.…”

mentioning

confidence: 99%

Dynamics of morphological changes in neural cell culture with a model of neurotrauma under the influence of conditioned media of the rat fetal brain neurogenic cells

Pedachenko¹,

Любич²,

Стайно³

et al. 2020

COT

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A potential strategy for recovery and regeneration of brain damage due to traumatic brain injury is considered to be the transplantation of neurogenic stem and/or progenitor cells (NSCs/NPCs). The key factors of the regenerative non-targeted effects of NSCs/NPCs (so-called bystander effects) include the signal molecules produced by them into the extracellular environment (secretome). The purpose is to study the regenerative bystander effects of rat fetal brain neurogenic cells (FBNCs) in the in vitro model of neurotrauma. Materials and methods. In cell culture of FBNCs from rat fetuses (E14-16), neurotrauma was modeled in vitro by mechanical scratching of monolayer and conditioned medium obtained from 24-h cultures of rat FBNCs was added. Cell phenotype was evaluated by morphological features and by immunocytochemical staining for Nestin and GFAP. The density and length of processes, migration capacity, the cell growth rate and monolayer density in the scratched area were compared. Morphometric study included analysis of the width of the scratched area, the number of migrating cells, the distance of migration and mitotic activity in the intact monolayer. Results. Under the conditions of the nutrient medium of standard composition in the scratched area the signs of endogenous regeneration are shown during 24-48 h of cultivation. The overgrowth of cell processes from monolayer and short distance migration of single undifferentiated or poorly differentiated cells were shown. In the next 72-96 h of observation, the degeneration of migrated cells and processes in the scratched area was detected. Under the influence of conditioned media from 24-h cultures of FBNCs by single addition immediately after scratching at dose of 0.1 mg/ml for protein content the stimulation of regeneration were detected up to 96 hours of cultivation. The migration of cell processes from the monolayer simultaneously with undifferentiated or poorly differentiated cells at 24 hours was shown. The formation of cell clusters and their differentiation (at 48 h), as well as migration of differentiated cells with partial or complete overgrowth of scratched area (72-96 h) were observed. The morphological signs of degeneration of migrated cells in the scratched area appeared only on the 8th day of cultivation. Conditioned media does not affect qualitative and quantitative properties of the culture of rat FBNCs in the intact area where mitotic activity was average. Conclusions. Conditioned medium from 24-h cultures of rat FBNC can stimulate reparation in the in vitro model of neurotrauma in neural cell culture for at least 7 days at a single addition, without affecting the cellular composition and mitotic activity of the intact monolayer.

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Paracrine Neuroprotective Effects of Neural Stem Cells on Glutamate-Induced Cortical Neuronal Cell Excitotoxicity

Cited by 14 publications

References 37 publications

Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia

Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia

Lanthanum Chloride Inhibits LPS Mediated Expressions of Pro-Inflammatory Cytokines and Adhesion Molecules in HUVECs: Involvement of NF-κB-Jmjd3 Signaling

Dynamics of morphological changes in neural cell culture with a model of neurotrauma under the influence of conditioned media of the rat fetal brain neurogenic cells

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