scholarly journals Antigenic and Genotypic Similarity between Primary Glioblastomas and Their Derived Neurospheres

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Valentina Caldera ◽  
Marta Mellai ◽  
Laura Annovazzi ◽  
Angela Piazzi ◽  
Michele Lanotte ◽  
...  
Keyword(s):  
Stem Cells ◽  
Genetic Alterations ◽  
Tumor Stem Cells ◽  
Primary Tumors ◽  
Immunodeficient Mice ◽  
Brain Tumor Stem Cells ◽  
Tumor Phenotype ◽  
Fetal Bovine ◽  
Primary Glioblastomas

Formation of neurospheres (NS) in cultures of glioblastomas (GBMs), with self-renewal, clonogenic capacities, and tumorigenicity following transplantation into immunodeficient mice, may denounce the existence of brain tumor stem cells (BTSCs) in vivo. In sixteen cell lines from resected primary glioblastomas, NS showed the same genetic alterations as primary tumors and the expression of stemness antigens. Adherent cells (AC), after adding 10% of fetal bovine serum (FBS) to the culture, were genetically different from NS and prevailingly expressed differentiation antigens. NS developed from a highly malignant tumor phenotype with proliferation, circumscribed necrosis, and high vessel density. Beside originating from transformed neural stem cells (NSCs), BTSCs may be contained within or correspond to dedifferentiated cells after mutation accumulation, which reacquire the expression of stemness antigens.

scholarly journals EGFR blockade in GBM brain tumor stem cells synergizes with JAK2/STAT3 pathway inhibition to abrogate compensatory mechanisms in vitro and in vivo

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Katharine V Jensen ◽  
Xiaoguang Hao ◽  
Ahmed Aman ◽  
H Artee Luchman ◽  
Samuel Weiss
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Compensatory Mechanism ◽  
Tumor Stem Cells ◽  
Egfr Inhibition ◽  
Stat3 Signaling ◽  
Brain Tumor Stem Cells ◽  
Xenograft Models

Abstract Background The EGFR pathway is frequently mutated in glioblastoma (GBM). However, to date, EGFR therapies have not demonstrated efficacy in clinical trials. Poor brain penetration of conventional inhibitors, lack of patient stratification for EGFR status, and mechanisms of resistance are likely responsible for the failure of EGFR-targeted therapy. We aimed to address these elements in a large panel of molecularly diverse patient-derived GBM brain tumor stem cells (BTSCs). Methods In vitro growth inhibition and on-target efficacy of afatinib, pacritinib, or a combination were assessed by cell viability, neurosphere formation, cytotoxicity, limiting dilution assays, and western blotting. In vivo efficacy was assessed with mass spectrometry, immunohistochemistry, magnetic resonance imaging, and intracranial xenograft models. Results We show that afatinib and pacritinib decreased BTSC growth and sphere-forming capacity in vitro. Combinations of the 2 drugs were synergistic and abrogated the activation of STAT3 signaling observed upon EGFR inhibition in vitro and in vivo. We further demonstrate that the brain-penetrant EGFR inhibitor, afatinib, improved survival in EGFRvIII mt orthotopic xenograft models. However, upregulation of the oncogenic STAT3 signaling pathway was observed following afatinib treatment. Combined inhibition with 2 clinically relevant drugs, afatinib and pacritinib, synergistically decreased BTSC viability and abrogated this compensatory mechanism of resistance to EGFR inhibition. A significant decrease in tumor burden in vivo was observed with the combinatorial treatment. Conclusions These data demonstrate that brain-penetrant combinatorial therapies targeting the EGFR and STAT3 signaling pathways hold therapeutic promise for GBM.

Molecular and cell biology of brain tumor stem cells: lessons from neural progenitor/stem cells

2008 ◽  
Vol 24 (3-4) ◽  
pp. E25 ◽  
Author(s):  
Zhigang Xie ◽  
Lawrence S. Chin
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Cell Fate ◽  
Cell Biology ◽  
Neural Progenitor ◽  
Tumor Stem Cells ◽  
Tumor Initiating Cells ◽  
Brain Tumor Stem Cells

✓ The results of studies conducted in the past several years have suggested that malignant brain tumors may harbor a small fraction of tumor-initiating cells that are likely to cause tumor recurrence. These cells are known as brain tumor stem cells (BTSCs) because of their multilineage potential and their ability to self-renew in vitro and to recapitulate original tumors in vivo. The understanding of BTSCs has been greatly advanced by knowledge of neural progenitor/stem cells (NPSCs), which are multipotent and self-renewing precursor cells for neurons and glia. In this article, the authors summarize evidence that genetic mutations that deregulate asymmetric cell division by affecting cell polarity, spindle orientation, or cell fate determinants may result in the conversion of NPSCs to BTSCs. In addition, they review evidence that BTSCs and normal NPSCs may reside in similar vascularized microenvironments, where similar evolutionarily conserved signaling pathways control their proliferation. Finally, they discuss preliminary evidence that mechanisms of BTSC-associated infiltrativeness may be similar to those underlying the migration of NPSCs and neurons.

Flow Cytometric Analysis of Brain Tumor Stem Cells

2018 ◽  
pp. 69-77
Author(s):  
Minomi K. Subapanditha ◽  
Ashley A. Adile ◽  
Chitra Venugopal ◽  
Sheila K. Singh
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Flow Cytometric Analysis ◽  
Tumor Stem Cells ◽  
Flow Cytometric ◽  
Brain Tumor Stem Cells

scholarly journals Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors

2019 ◽  
Author(s):  
Rongqun Guo ◽  
Fangxiao Hu ◽  
Qitong Weng ◽  
Cui Lv ◽  
Hongling Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Time Window ◽  
Immune Surveillance ◽  
Cell Stage ◽  
Immunodeficient Mice ◽  
Cell Transcriptome ◽  
T Lymphopoiesis

ABSTRACTAchievement of immunocompetent and therapeutic T lymphopoiesis from pluripotent stem cells is a central aim in T cell regenerative medicine. To date, preferentially regenerating T lymphopoiesis in vivo from pluripotent stem cells (PSC) remains a practical challenge. Here we documented that synergistic and transient expression of Runx1 and Hoxa9 restricted in the time window of endothelial to hematopoietic transition and hematopoietic maturation stages induced in vitro from PSC (iR9-PSC) preferentially generated engraftable hematopoietic progenitors capable of homing to thymus and developing into mature T (iT) cells in primary and secondary immunodeficient recipients. Single-cell transcriptome and functional analyses illustrated the cellular trajectory of T lineage induction from PSC, unveiling the T-lineage specification determined at as early as hemogenic endothelial cell stage and identifying the bona fide pre-thymic progenitors. The iT cells distributed normally in central and peripheral lymphoid organs and exhibited abundant TCRαβ repertoire. The regenerative T lymphopoiesis rescued the immune-surveillance ability in immunodeficient mice. Furthermore, gene-edited iR9-PSC produced tumor-specific-T cells in vivo that effectively eradicated tumor cells. This study provides insight into universal generation of functional and therapeutic T lymphopoiesis from the unlimited and editable PSC source.

scholarly journals Hematopoietic stem/progenitor cells, generation of induced pluripotent stem cells, and isolation of endothelial progenitors from 21- to 23.5-year cryopreserved cord blood

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4773-4777 ◽  
Author(s):  
Hal E. Broxmeyer ◽  
Man-Ryul Lee ◽  
Giao Hangoc ◽  
Scott Cooper ◽  
Nutan Prasain ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Proliferative Potential ◽  
Hematopoietic Stem ◽  
Immunodeficient Mice ◽  
Induced Pluripotent

Abstract Cryopreservation of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) is crucial for cord blood (CB) banking and transplantation. We evaluated recovery of functional HPC cryopreserved as mononuclear or unseparated cells for up to 23.5 years compared with prefreeze values of the same CB units. Highly efficient recovery (80%-100%) was apparent for granulocyte-macrophage and multipotential hematopoietic progenitors, although some collections had reproducible low recovery. Proliferative potential, response to multiple cytokines, and replating of HPC colonies was extensive. CD34+ cells isolated from CB cryopreserved for up to 21 years had long-term (≥ 6 month) engrafting capability in primary and secondary immunodeficient mice reflecting recovery of long-term repopulating, self-renewing HSCs. We recovered functionally responsive CD4+ and CD8+ T lymphocytes, generated induced pluripotent stem (iPS) cells with differentiation representing all 3 germ cell lineages in vitro and in vivo, and detected high proliferative endothelial colony forming cells, results of relevance to CB biology and banking.

Brain Tumor Stem Cells

2014 ◽  
pp. 23-34
Author(s):  
N. Sumru Bayin ◽  
Aram S. Modrek ◽  
Dimitris G. Placantonakis
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Tumor Stem Cells ◽  
Brain Tumor Stem Cells

Brain Tumor Stem Cells

2009 ◽  
pp. 241-259 ◽  
Author(s):  
Christian Nern ◽  
Daniel Sommerlad ◽  
Till Acker ◽  
Karl H. Plate
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Tumor Stem Cells ◽  
Brain Tumor Stem Cells
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