scholarly journals Neural Stem Cells of the Subventricular Zone as the Origin of Human Glioblastoma Stem Cells. Therapeutic Implications

2019 ◽  
Vol 9 ◽  
Author(s):  
Esperanza R. Matarredona ◽  
Angel M. Pastor
2021 ◽  
Vol 69 (5) ◽  
pp. 349-364 ◽  
Author(s):  
Vashendriya V.V. Hira ◽  
Remco J. Molenaar ◽  
Barbara Breznik ◽  
Tamara Lah ◽  
Eleonora Aronica ◽  
...  

Glioblastoma usually recurs after therapy consisting of surgery, radiotherapy, and chemotherapy. Recurrence is at least partly caused by glioblastoma stem cells (GSCs) that are maintained in intratumoral hypoxic peri-arteriolar microenvironments, or niches, in a slowly dividing state that renders GSCs resistant to radiotherapy and chemotherapy. Because the subventricular zone (SVZ) is a major niche for neural stem cells (NSCs) in the brain, we investigated whether GSCs are present in the SVZ at distance from the glioblastoma tumor. We characterized the SVZ of brains of seven glioblastoma patients using fluorescence immunohistochemistry and image analysis. NSCs were identified by CD133 and SOX2 but not CD9 expression, whereas GSCs were positive for all three biomarkers. NSCs were present in all seven samples and GSCs in six out of seven samples. The SVZ in all samples were hypoxic and expressed the same relevant chemokines and their receptors as GSC niches in glioblastoma tumors: stromal-derived factor-1α (SDF-1α), C-X-C receptor type 4 (CXCR4), osteopontin, and CD44. In conclusion, in glioblastoma patients, GSCs are present at distance from the glioblastoma tumor in the SVZ. These findings suggest that GSCs in the SVZ niche are protected against radiotherapy and chemotherapy and protected against surgical resection due to their distant localization and thus may contribute to tumor recurrence after therapy.


2011 ◽  
Vol 89 (8) ◽  
pp. 1185-1193 ◽  
Author(s):  
Gadi Turgeman ◽  
Adi Pinkas ◽  
Theodore A. Slotkin ◽  
Matanel Tfilin ◽  
Rachel Langford ◽  
...  

2017 ◽  
Vol 222 (6) ◽  
pp. 2855-2876 ◽  
Author(s):  
Valentina Mastrorilli ◽  
Chiara Scopa ◽  
Daniele Saraulli ◽  
Marco Costanzi ◽  
Raffaella Scardigli ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0172884 ◽  
Author(s):  
Julia Pollak ◽  
Karan G. Rai ◽  
Cory C. Funk ◽  
Sonali Arora ◽  
Eunjee Lee ◽  
...  

2020 ◽  
Author(s):  
Huanhuan Sha ◽  
Peipei Peng ◽  
Bing Li ◽  
Guohua Wei ◽  
Juan Wang ◽  
...  

Abstract Background: Recently, the number of neonatal patients receiving surgery under general anesthesia has increased. Ketamine disrupts the proliferation and differentiation of developing neural stem cells (NSCs). Therefore, the safe use of ketamine in pediatric anesthesia has been an issue of increasing concern among anesthesiologists and the children’s parents. Dexmedetomidine (DEX) is widely used in sedation, as an antianxiety agent and for analgesia. DEX has recently been shown to provide neuroprotection against anesthetic-induced neurotoxicity in the developing brain. The aim of this in vivo study was to investigate whether DEX exerted neuroprotective effects on the proliferation and differentiation of NSCs in the subventricular zone (SVZ) following neonatal ketamine exposure. Methods: Postnatal day 7 (PND-7) male Sprague-Dawley rats were equally divided into the following 5 groups: Control group (n=8), Ketamine group (n=8), 1 μg/kg DEX+Ketamine group (n=8), 5 μg/kg DEX+Ketamine group (n=8) and 10 μg/kg DEX+Ketamine group (n=8). The proliferation and differentiation of NSCs in the SVZ were assessed using immunostaining with BrdU incorporation. The levels of Nestin and β-tubulin III in the SVZ were measured using Western blot analyses. Apoptosis was assessed by detecting the levels of the cleaved caspase-3 protein using Western blotting. Results: Neonatal ketamine exposure significantly inhibited NSC proliferation and astrocytic differentiation in the SVZ, and neuronal differentiation was markedly increased. Furthermore, pretreatment with moderate (5 μg/kg) or high doses (10 μg/kg) of DEX reversed the ketamine-induced disturbances in the proliferation and differentiation of NSCs. Meanwhile, neonatal ketamine exposure significantly decreased the expression of Nestin and increased the expression of β-tubulin III in the SVZ compared with the Control group. Treatment with 10 μg/kg DEX notably reversed the ketamine-induced changes in the levels of Nestin and β-tubulin III. In addition, a pretreatment with 10 μg/kg DEX before ketamine anesthesia prevented apoptosis in the SVZ induced by neonatal ketamine exposure. Conclusions: Based on our findings, DEX may exert neuroprotective effects on the proliferation and differentiation of NSCs in the SVZ of neonatal rats in a repeated ketamine anesthesia model.


ASN NEURO ◽  
2013 ◽  
Vol 5 (3) ◽  
pp. AN20120032 ◽  
Author(s):  
Dhivyaa Alagappan ◽  
Murugabaskar Balan ◽  
Yuhui Jiang ◽  
Rachel B. Cohen ◽  
Sergei V. Kotenko ◽  
...  

2009 ◽  
pp. 255-270 ◽  
Author(s):  
Yang D. Teng ◽  
Serdar Kabatas ◽  
Jianxue Li ◽  
Dustin R. Wakeman ◽  
Evan Y. Snyder ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 913 ◽  
Author(s):  
Jana Konířová ◽  
Lukáš Cupal ◽  
Šárka Jarošová ◽  
Anna Michaelidesová ◽  
Jana Vachelová ◽  
...  

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.


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