scholarly journals Generation of in vivo neural stem cells using partially reprogrammed cells defective in in vitro differentiation potential

Oncotarget ◽  
2017 ◽  
Vol 8 (10) ◽  
pp. 16456-16462 ◽  
Author(s):  
Jong Soo Kim ◽  
Yean Ju Hong ◽  
Hyun Woo Choi ◽  
Hyuk Song ◽  
Sung June Byun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
In Vitro Differentiation ◽  
Differentiation Potential

scholarly journals Bio-electrosprayed human neural stem cells are viable and maintain their differentiation potential

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 267
Author(s):  
Citlali Helenes González ◽  
Suwan N. Jayasinghe ◽  
Patrizia Ferretti
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Gene Expression Analysis ◽  
Molecular Level ◽  
Human Central Nervous System ◽  
Differentiation Potential ◽  
Human Neural Stem Cells ◽  
First Time

Background: Bio-electrospray (BES) is a jet-based delivery system driven by an electric field that has the ability to form micro to nano-sized droplets. It holds great potential as a tissue engineering tool as it can be used to place cells into specific patterns. As the human central nervous system (CNS) cannot be studied in vivo at the cellular and molecular level, in vitro CNS models are needed. Human neural stem cells (hNSCs) are the CNS building block as they can generate both neurones and glial cells. Methods: Here we assessed for the first time how hNSCs respond to BES. To this purpose, different hNSC lines were sprayed at 10 kV and their ability to survive, grow and differentiate was assessed at different time points. Results: BES induced only a small and transient decrease in hNSC metabolic activity, from which the cells recovered by day 6, and no significant increase in cell death was observed, as assessed by flow cytometry. Furthermore, bio-electrosprayed hNSCs differentiated as efficiently as controls into neurones, astrocytes and oligodendrocytes, as shown by morphological, protein and gene expression analysis. Conclusions: This study highlights the robustness of hNSCs and identifies BES as a suitable technology that could be developed for the direct deposition of these cells in specific locations and configurations.

scholarly journals Bio-electrosprayed human neural stem cells are viable and maintain their differentiation potential

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 267
Author(s):  
Citlali Helenes González ◽  
Suwan N. Jayasinghe ◽  
Patrizia Ferretti
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Gene Expression Analysis ◽  
Molecular Level ◽  
Human Central Nervous System ◽  
Differentiation Potential ◽  
Human Neural Stem Cells ◽  
First Time

Background: Bio-electrospray (BES) is a jet-based delivery system driven by an electric field that has the ability to form micro to nano-sized droplets. It holds great potential as a tissue engineering tool as it can be used to place cells into specific patterns. As the human central nervous system (CNS) cannot be studied in vivo at the cellular and molecular level, in vitro CNS models are needed. Human neural stem cells (hNSCs) are the CNS building block as they can generate both neurones and glial cells. Methods: Here we assessed for the first time how hNSCs respond to BES. To this purpose, different hNSC lines were sprayed at 10 kV and their ability to survive, grow and differentiate was assessed at different time points. Results: BES induced only a small and transient decrease in hNSC metabolic activity, from which cells recovered by day 6, and no significant increase in cell death was observed, as assessed by flow cytometry. Furthermore, bio-electrosprayed hNSCs differentiated as efficiently as controls into neurones, astrocytes and oligodendrocytes as shown by morphological, protein and gene expression analysis. Conclusions: This study highlights the robustness of hNSCs and identifies BES as a suitable technology that could be developed for the direct deposition of these cells in specific locations and configurations.

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

scholarly journals Comparison of Chondral Defects Repair with In Vitro and In Vivo Differentiated Mesenchymal Stem Cells

2007 ◽  
Vol 16 (8) ◽  
pp. 823-832 ◽  
Author(s):  
Hongbin Fan ◽  
Haifeng Liu ◽  
Rui Zhu ◽  
Xusheng Li ◽  
Yuming Cui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cartilage Tissue ◽  
Burst Release ◽  
In Vitro Differentiation ◽  
Chondral Defects ◽  
In Vivo Differentiation ◽  
Repair Group

The purpose of this study was to compare chondral defects repair with in vitro and in vivo differentiated mesenchymal stem cells (MSCs). A novel PLGA-gelatin/chondroitin/hyaluronate (PLGA-GCH) hybrid scaffold with transforming growth factor-β1 (TGF-β1)-impregnated microspheres (MS-TGF) was fabricated to mimic the extracellular matrix. MS-TGF showed an initial burst release (22.5%) and a subsequent moderate one that achieved 85.1% on day 21. MSCs seeded on PLGA-GCH/MS-TGF or PLGA-GCH were incubated in vitro and showed that PLGA-GCH/MS-TGF significantly augmented proliferation of MSCs and glycosaminoglycan synthesis compared with PLGA-GCH. Then MSCs seeded on PLGA-GCH/MS-TGF were implanted and differentiated in vivo to repair chondral defect on the right knee of rabbit (in vivo differentiation repair group), while the contralateral defect was repaired with in vitro differentiated MSCs seeded on PLGA-GCH (in vitro differentiation repair group). The histology observation demonstrated that in vivo differentiation repair showed better chondrocyte morphology, integration, and subchondral bone formation compared with in vitro differentiation repair 12 and 24 weeks postoperatively, although there was no significant difference after 6 weeks. The histology grading score comparison also demonstrated the same results. The present study implies that in vivo differentiation induced by PLGA-GCH/MS-TGF and the host microenviroment could keep chondral phenotype and enhance repair. It might serve as another way to induce and expand seed cells in cartilage tissue engineering.

scholarly journals High glucose induces early senescence in adipose-derived stem cells by accelerating p16 and mTOR

2019 ◽  
Vol 6 (6) ◽  
pp. 3213-3221
Author(s):  
Hieu Liem Pham ◽  
Phuc Van Pham
Keyword(s):  
Stem Cells ◽  
High Glucose ◽  
Glucose Concentration ◽  
Culture Medium ◽  
Diabetic Patients ◽  
Adipose Derived Stem Cells ◽  
Differentiation Potential ◽  
Normal Glucose

Introduction: The senescence of stem cells is the primary reason that causes aging of stem cell-containing tissues. Some hypotheses have suggested that high glucose concentration in diabetic patients is the main factor that causes senescence of cells in those patients. This study aimed to evaluate the effects of high glucose concentrations on the senescence of adipose-derived stem cells (ADSCs). Methods: ADSCs were isolated and expanded from human adipose tissues. They were characterized and confirmed as mesenchymal stem cells (MSCs) by expression of surface markers, their shape, and in vitro differentiation potential. They were then cultured in 3 different media- that contained 17.5 mM, 35 mM, or 55 mM of D-glucose. The senescent status of ADSCs was recorded by the expression of the enzyme beta-galactosidase, cell proliferation, and doubling time. Real-time RT-PCR was used to evaluate the expression of p16, p21, p53 and mTOR. Results: The results showed that high glucose concentrations (35 mM and 55 mM) in the culture medium induced senescence of human ADSCs. The ADSCs could progress to the senescent status quicker than those cultured in the lower glucose-containing medium (17.5 mM). The senescent state was related to the up-regulation of p16 and mTOR genes. Conclusion: These results suggest that high glucose in culture medium can trigger the expression of p16 and mTOR genes which cause early senescence in ADSCs. Therefore, ADSCs should be cultured in low glucose culture medium, or normal glucose concentration, to extend their life in vitro as well as in vivo.  

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
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