Combination of bFGF, heparin and laminin induce the generation of dopaminergic neurons from rat neural stem cells both in vitro and in vivo

2007 ◽  
Vol 255 (1-2) ◽  
pp. 81-86 ◽  
Author(s):  
Yiqun Yu ◽  
Shuting Gu ◽  
Hai Huang ◽  
Tieqiao Wen
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Dopaminergic Neurons

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 > 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 > 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< 0.05) in GBM, as well as a significant survival benefit in patient datasets when downregulated (p< 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< 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< 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.

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

scholarly journals BMP/SMAD Pathway Promotes Neurogenesis of Midbrain Dopaminergic Neurons In Vivo and in Human Induced Pluripotent and Neural Stem Cells

2018 ◽  
Vol 38 (7) ◽  
pp. 1662-1676 ◽  
Author(s):  
Vukasin M. Jovanovic ◽  
Ahmad Salti ◽  
Hadas Tilleman ◽  
Ksenija Zega ◽  
Marin M. Jukic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Dopaminergic Neurons ◽  
Smad Pathway ◽  
Midbrain Dopaminergic Neurons ◽  
Induced Pluripotent

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
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