scholarly journals Transplantation of neural stem cells in the mouse model of ischemic brain stroke and expression of genes involved in programmed cell death

2018 ◽  
Vol 59 (5) ◽  
pp. 203-212
Author(s):  
Valentina Hribljan ◽  
Iva Salamon ◽  
Arijana Đemaili ◽  
Ivan Alić ◽  
Dinko Mitrečić
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Mouse Model ◽  
Neural Stem Cells ◽  
Ischemic Brain ◽  
Expression Of Genes ◽  
Brain Stroke

scholarly journals TMOD-18. TARGETING THE PI3K/AKT PATHWAY IN MYCN AMPLIFIED HIGH GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii231-ii232
Author(s):  
Katharine Halligan ◽  
Ann-Catherine Stanton ◽  
Matthew Halbert ◽  
Brian Golbourn ◽  
Stephen Mack ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Suppressor ◽  
Mouse Model ◽  
Protein Expression ◽  
Neural Stem Cells ◽  
Tumor Suppressor Genes ◽  
Akt Pathway ◽  
High Grade ◽  
Suppressor Genes ◽  
High Grade Gliomas

Abstract Pediatric glioblastoma (pGBM) are incurable brain tumors with overall poor prognosis and response to treatments due to molecular and epigenetic heterogeneity. In particular, the MYCN subtype of pGBM are a highly aggressive form of GBM with a dismal median survival of only 14 months. Furthermore, this subtype is enriched with loss of the tumor suppressor genes TP53 and PTEN, leading to aberrantly active PI3K-AKT signaling pathway and DNA-checkpoint abnormalities. Here, we report the generation of a novel syngeneic mouse model that recapitulates the features of the MYCN subtype of pGBM. We isolated Sox2-Cre neural stem cells from C57BL/6 mice and transduced inverted retroviral-cassettes of the murine Mycn oncogene simultaneously with shRNA targeting tumor suppressor genes p53 and Pten. Retroviral-cassettes are flanked by tandem LoxP sites arranged so that Cre recombinase expression inverts the cassettes in frame allowing for MYCN protein expression and loss of the P53/PTEN proteins. Transgene activation is accompanied with selectable cell surface markers and fluorescent tags enabling for fluorescent activated cell sorting (FACS) of the desired cell populations. Neural stem cells with MYCN protein expression and concurrent silencing of P53 and PTEN protein (NPP cells) result in significantly increased proliferation and activation of PI3K-AKT pathway as compared to control neural stem cells and have. Injection of NPP cells into the forebrain of immune competent C57BL/6 mice result in the formation of invasive high-grade gliomas with a lethal phenotype at ~50 days post injection. Using several next generation brain penetrant small molecule inhibitors of the PI3K-AKT pathway, we show inhibition of tumorigenesis in vitro. Moreover, we have identified several novel mechanisms of PI3KAKT treatment resistance and are currently identifying therapies that may overcome this resistance through RNA seq analysis. In summary, well defined genetic drivers of GBM can lead to informed mouse model generation to test promising therapies.

31 Neural stem cells and cell death

2003 ◽  
Vol 144 ◽  
pp. s11 ◽  
Author(s):  
S. Ceccatelli ◽  
C. Tamm ◽  
E. Sleeper ◽  
S. Orrenius ◽  
E.Y. Snyder
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Neural Stem Cells

Multimodal Actions of Neural Stem Cells in a Mouse Model of ALS: A Meta-Analysis

2012 ◽  
Vol 4 (165) ◽  
pp. 165ra164-165ra164 ◽  
Author(s):  
Y. D. Teng ◽  
S. C. Benn ◽  
S. N. Kalkanis ◽  
J. M. Shefner ◽  
R. C. Onario ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mouse Model ◽  
Neural Stem Cells ◽  
Meta Analysis

scholarly journals Sensitive-stage embryo irradiation affects embryonic neuroblasts and adult motor function

2022 ◽  
Author(s):  
Ram Wagle ◽  
Young-Han Song
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Neural Stem Cells ◽  
Motor Function ◽  
Radiation Sensitivity ◽  
Embryonic Lethality ◽  
Apoptotic Cells ◽  
Childhood Malignancies ◽  
Sensitive Stage ◽  
Stage Embryo

Abstract Background Cranial radiation therapy for treating childhood malignancies in the central nervous system or accidental radiation exposure may result in neurological side effects in surviving adults. As tissue homeostasis is maintained by stem cells, understanding the effect of radiation on neural stem cells will provide clues for managing the neurological effects. Drosophila embryos were used as a model system whose sensitivity to irradiation-induced cell death changes from the sensitive to resistant stage during development. Objective Drosophila embryos at the radiation-sensitive stage were irradiated at various doses and the radiation sensitivity was tested regarding the appearance of apoptotic cells in the embryos and the embryonic lethality. Cell fates of the neural stem cells called neuroblasts (NBs) and adult motor function after irradiation were also investigated. Result Irradiation of Drosophila embryos at the radiation-sensitive stage resulted in a dose-dependent increase in the number of embryos containing apoptotic cells 75 min after treatment starting at 3 Gy. Embryonic lethality assayed by hatch rate was induced by 1 Gy irradiation, which did not induce cell death. Notably, no apoptosis was detected in NBs up to 2 h after irradiation at doses as high as 40 Gy. At 3 h after irradiation, as low as 3 Gy, the number of NBs marked by Dpn and Klu was decreased by an unidentified mechanism regardless of the cell death status of the embryo. Furthermore, embryonic irradiation at 3 Gy, but not 1 Gy, resulted in locomotor defects in surviving adults. Conclusion Embryonic NBs survived irradiation at doses as high as 40 Gy, while cells in other parts of the embryos underwent apoptosis at doses higher than 3 Gy within 2 h after treatment. Three hours after exposure to a minimum dose of 3 Gy, the number of NBs marked by Dpn and Klu decreased, and the surviving adults exhibited defects in locomotor ability.

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