The carbocyanine dye DiD labels in vitro and in vivo neural stem cells of the subventricular zone as well as myelinated structures following in vivo injection in the lateral ventricle

2015 ◽  
Vol 94 (2) ◽  
pp. 139-148 ◽  
Author(s):  
Dario Carradori ◽  
Kristell Barreau ◽  
Joël Eyer
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Lateral Ventricle ◽  
Carbocyanine Dye

scholarly journals Activated Neural Stem Cells Contribute to Stroke-Induced Neurogenesis and Neuroblast Migration toward the Infarct Boundary in Adult Rats

2004 ◽  
Vol 24 (4) ◽  
pp. 441-448 ◽  
Author(s):  
Ruilan Zhang ◽  
Zhenggang Zhang ◽  
Lei Wang ◽  
Ying Wang ◽  
Anton Gousev ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Proliferating Cells ◽  
Adult Rats ◽  
Antimitotic Agent ◽  
Neuroblast Migration ◽  
Ipsilateral Striatum

Stroke increases neurogenesis. The authors investigated whether neural stem cells or progenitor cells in the adult subventricular zone (SVZ) of rats contribute to stroke-induced increase in neurogenesis. After induction of stroke in rats, the numbers of cells immunoreactive to doublecortin, a marker for immature neurons, increased in the ipsilateral SVZ and striatum. Infusion of an antimitotic agent (cytosine-β-D-arabiofuranoside, Ara-C) onto the ipsilateral cortex eliminated more than 98% of actively proliferating cells in the SVZ and doublecortin-positive cells in the ipsilateral striatum. However, doublecortin-positive cells rapidly replenished after antimitotic agent depletion of actively proliferating cells. Depleting the numbers of actively proliferating cells in vivo had no effect on the numbers of neurospheres formed in vitro, yet the numbers of neurospheres derived from stroke rats significantly ( P < 0.05) increased. Neurospheres derived from stroke rats self-renewed and differentiated into neurons and glia. In addition, doublecortin-positive cells generated in the SVZ migrated in a chainlike structure toward ischemic striatum. These findings indicate that in the adult stroke brain, increases in recruitment of neural stem cells contribute to stroke-induced neurogenesis, and that newly generated neurons migrate from the SVZ to the ischemic striatum.

scholarly journals EXTH-07. TUMOR-HOMING INDUCED NEURAL STEM CELLS SECRETING A CYTOTOXIC PAYLOAD AS AN ADJUVANT TREATMENT FOR NON-SMALL CELL LUNG CANCER BRAIN METASTASES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii88-ii88
Author(s):  
Alison Mercer-Smith ◽  
Wulin Jiang ◽  
Alain Valdivia ◽  
Juli Bago ◽  
Scott Floyd ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Metastases ◽  
Neural Stem Cells ◽  
Adjuvant Treatment ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Homing ◽  
Induced Neural Stem Cells

Abstract INTRODUCTION Non-small cell lung cancer (NSCLC) is the most common cancer to form brain metastases. Radiation treatment is standard-of-care, but recurrence is still observed in 40% of patients. An adjuvant treatment is desperately needed to track down and kill tumor remnants after radiation. Tumoritropic neural stem cells (NSCs) that can home to and deliver a cytotoxic payload offer potential as such an adjuvant treatment. Here we show the transdifferentiation of human fibroblasts into tumor-homing induced neural stem cells (hiNSCs) that secrete the cytotoxic protein TRAIL (hiNSC-TRAIL) and explore the use of hiNSC-TRAIL to treat NSCLC brain metastases. METHODS To determine the migratory capacity of hiNSCs, hiNSCs were infused intracerebroventricularly (ICV) into mice bearing established bilateral NSCLC H460 brain tumors. hiNSC accumulation at tumor foci was monitored using bioluminescent imaging and post-mortem fluorescent analysis. To determine synergistic effects of radiation with TRAIL on NSCLC, we performed in vitro co-culture assays and isobologram analysis. In vivo, efficacy was determined by tracking the progression and survival of mice bearing intracranial H460 treated with hiNSC-TRAIL alone or in combination with 2 Gy radiation. RESULTS/CONCLUSION Following ICV infusion, hiNSCs persisted in the brain for &gt; 1 week and migrated from the ventricles to colocalize with bilateral tumor foci. In vitro, viability assays and isobologram analysis revealed the combination treatment of hiNSC-TRAIL and 2 Gy radiation induced synergistic killing (combination index=0.64). In vivo, hiNSC-TRAIL/radiation combination therapy reduced tumor volumes &gt; 90% compared to control-treated animals while radiation-only and hiNSC-TRAIL-only treated mice showed 21% and 52% reduced volumes, respectively. Dual-treatment extended survival 40%, increasing survival from a median of 20 days in controls to 28 days in the treatment group. These results suggest hiNSC-TRAIL can improve radiation therapy for NSCLC brain metastases and could potentially improve outcomes for patients suffering from this aggressive form of cancer.

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

CBIO-13. THOC1 DRIVES GBM AGGRESSION THROUGH MODULATION OF R-LOOPS AND GENOMIC STABILITY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi29-vi30
Author(s):  
Shreya Budhiraja ◽  
Shivani Baisiwala ◽  
Khizar Nandoliya ◽  
Li Chen ◽  
Crismita Dmello ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Neural Stem Cells ◽  
Histone Deacetylase ◽  
Genomic Stability ◽  
Loop Formation ◽  
Driver Genes ◽  
A Genome

Abstract Glioblastoma (GBM) is the most aggressive and common type of adult malignant brain tumor, with a median survival of only 21 months. To identify which genes drive its highly aggressive phenotype, we performed a genome-wide CRISPR-Cas9 knockout screen. Results showed substantial enrichment of ~160 novel essential oncogenic driver genes and pathways, including a previously unstudied gene THOC1—involved in RNA processing—that showed significant elevations in expression at RNA and protein levels (p&lt; 0.05) in GBM, as well as a significant survival benefit in patient datasets when downregulated (p&lt; 0.05). Knocking out THOC1 resulted in cell death in multiple GBM patient-derived xenograft (PDX) lines and extended survival compared to the controls (p&lt; 0.01) in vivo. Overexpression of THOC1 in neural stem cells resulted in transformation to a cancerous phenotype, as evidenced by sphere formation in a soft agar assay (p&lt; 0.01) and in vivo tumor engraftment assays. Further investigation of THOC1 through immunoprecipitation in neural stem cells and multiple GBM lines showed significant interaction in GBM with histone deacetylase complex SIN3A, involved in recruiting major histone deacetylases in order to close the DNA and prevent the accumulation of R-loops, RNA:DNA hybrids that pose a threat to genomic stability. Additional investigation revealed that THOC1-knockdowns in vitro induced R-loop formation and DNA damage, while THOC1-overexpression in vitro resulted in an untenable decrease in R-loops and DNA damage, suggesting that the THOC1-SIN3A axis is elevated in GBM in order to prevent the accumulation of genotoxic R-loops. Additionally, histone deacetylase activity was shown to be elevated in THOC1-overexpression conditions and reduced in THOC1-knockdown conditions, confirming that the THOC1-SIN3A axis functions to prevent R-loop accumulation through the epigenetic regulation. In summary, our whole-genome CRISPR-Cas9 knockout screen has identified a promising therapeutic target for GBM—a disease desperately in need of therapeutic innovations.

scholarly journals Differentiation Induction as a Response to Irradiation in Neural Stem Cells In Vitro

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 913 ◽  
Author(s):  
Jana Konířová ◽  
Lukáš Cupal ◽  
Šárka Jarošová ◽  
Anna Michaelidesová ◽  
Jana Vachelová ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Brain Cancer ◽  
Subventricular Zone ◽  
Transcriptional Activity ◽  
Radiation Induced ◽  
Induction Of Differentiation ◽  
Stem Cell Populations ◽  
Neurocognitive Decline

Radiotherapy plays a significant role in brain cancer treatment; however, the use of this therapy is often accompanied by neurocognitive decline that is, at least partially, a consequence of radiation-induced damage to neural stem cell populations. Our findings describe features that define the response of neural stem cells (NSCs) to ionizing radiation. We investigated the effects of irradiation on neural stem cells isolated from the ventricular-subventricular zone of mouse brain and cultivated in vitro. Our findings describe the increased transcriptional activity of p53 targets and proliferative arrest after irradiation. Moreover, we show that most cells do not undergo apoptosis after irradiation but rather cease proliferation and start a differentiation program. Induction of differentiation and the demonstrated potential of irradiated cells to differentiate into neurons may represent a mechanism whereby damaged NSCs eliminate potentially hazardous cells and circumvent the debilitating consequences of cumulative DNA damage.

Superparamagnetic iron oxide labeling of neural stem cells and 4.7T MRI tracking in vivo and in vitro

2007 ◽  
Vol 27 (1) ◽  
pp. 107-110 ◽  
Author(s):  
Wenzhen Zhu ◽  
Xiang Li ◽  
Zhouping Tang ◽  
Suiqiang Zhu ◽  
Jianpin Qi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Iron Oxide ◽  
Neural Stem Cells ◽  
Superparamagnetic Iron Oxide

The synthetic NCAM mimetic peptide FGL mobilizes neural stem cells in vitro and in vivo

2014 ◽  
Vol 10 (4) ◽  
pp. 539-547 ◽  
Author(s):  
Rebecca Klein ◽  
Stefan Blaschke ◽  
Bernd Neumaier ◽  
Heike Endepols ◽  
Rudolf Graf ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Mimetic Peptide

Abstract 4759: Integrated in vitro and in vivo screening of tumor and normal neural stem cells identifies potential new treatments of ependymoma

2011 ◽  
Author(s):  
Jennifer M. Atkinson ◽  
Anang A. Shelat ◽  
Tanya A. Kranenburg ◽  
Angel M. Carcaboso ◽  
Alexander Arnold ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
In Vivo Screening ◽  
New Treatments

193 ROBUST PROPAGATION OF SELF-RENEWING PORCINE NEURAL STEM CELLS ISOLATED FROM TRANSGENIC PIGS WITH A GFAP-CreERT2 SYSTEM CAPABLE OF CONTROLLING THE EXPRESSION OF EGFP GENES

2017 ◽  
Vol 29 (1) ◽  
pp. 205
Author(s):  
E. Kim ◽  
H. Kim ◽  
S.-H. Hyun
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Central Nervous System Diseases ◽  
Transgenic Pigs ◽  
Ample Evidence ◽  
Viable Cells ◽  
Promising Source ◽  
Dna Recombinase

Ample evidence has demonstrated the important roles of pigs because their anatomical, immunologic, and physiological characteristics are fairly similar to humans. In particular, their gyrencephalic brain are more comparable to humans than rodents with similar grey and white matter composition and size. In this study, we isolated and propagated the neural stem cells (GFAP-CreERT2-NSCs) from the transgenic piglet with expression of CreERT2, a fusion protein of the DNA recombinase Cre and mutated ligand-binding domain of the human oestrogen receptor, under the control of the GFAP promoter. The primary culture from tissue of porcine CreERT2 brain led to floating spherical masses of cells that revealed similar morphology and size distribution to neurospheres reported by previous studies. Quantitative analysis indicated a yield of 2.50 ± 0.44 primary spheres per 1,000 viable cells from the neocortex, versus 12.92 ± 1.67 primary spheres per 1,000 viable cells from the periventricular region (PVR) including subventricular zone. Secondary spheres (6.67 ± 1.10 spheres from neocortex versus 23.08 ± 1.96 spheres from PVR cells) were formed from primary spheres at 10 days after passage. Tertiary spheres (8.42 ± 0.99 spheres from neocortex versus 23.08 ± 1.91 spheres from PVR cells) could also be obtained after a second passage, indicating that they were proliferating in vitro. The CreERT2-NSCs showed normal 36+XY karyotype and representative NSC markers, such as NESTIN, SOX2, and VIMENTIN. After differentiation, we were able to obtain populations of astrocytes and neurons expressing GFAP and TUJ1, respectively. In summary, we verified and propagated the isolated GFAP promoter-driven CreERT2-NSCs, which would be considered a promising source of cells for treatment of central nervous system diseases.

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