Glioma cancer stem cells and their role in therapy

Altaner, Č

doi:10.4267/2042/48156

Cited by 3 publications

(4 citation statements)

References 61 publications

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“…Therapeutic failure is caused by the highly invasive character of glioblastoma cells, deep dispersion of tumor cells into surrounding normal tissue and the presence of chemo‐ and radiotherapy resistant glioblastoma stem‐like cells (GSCs)—cells initiating glioblastoma growth (for a review, see Ref. ). Extensive neovascularization of tumor tissue and the presence of abundant hypoxic regions provide a perivascular niche for GSCs in the main tumor mass.…”

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confidence: 99%

Complete regression of glioblastoma by mesenchymal stem cells mediated prodrug gene therapy simulating clinical therapeutic scenario

Altaner

Altanerová²,

Cihova

et al. 2013

Intl Journal of Cancer

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Suicide gene therapy mediated by mesenchymal stem cells with their ability to engraft into tumors makes these therapeutic stem cells an attractive tool to activate prodrugs directly within the tumor mass. In this study, we evaluated the therapeutic efficacy of human mesenchymal stem cells derived from bone marrow and from adipose tissue, engineered to express the suicide gene cytosine deaminase::uracil phosphoribosyltransferase to treat intracerebral rat C6 glioblastoma in a simulated clinical therapeutic scenario. Intracerebrally grown glioblastoma was treated by resection and subsequently with single or repeated intracerebral inoculations of therapeutic stem cells followed by a continuous intracerebroventricular delivery of 5-fluorocytosine using an osmotic pump. Kaplan-Meier survival curves revealed that surgical resection of the tumor increased the survival time of the resected animals depending on the extent of surgical intervention. However, direct injections of therapeutic stem cells into the brain tissue surrounding the postoperative resection cavity led to a curative outcome in a significant number of treated animals. Moreover, the continuous supply of therapeutic stem cells into the brain with growing glioblastoma by osmotic pumps together with continuous prodrug delivery also proved to be therapeutically efficient. We assume that observed curative therapy of glioblastoma by stem cell-mediated prodrug gene therapy might be caused by the destruction of both tumor cells and the niche where glioblastoma initiating cells reside.

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confidence: 99%

Complete regression of glioblastoma by mesenchymal stem cells mediated prodrug gene therapy simulating clinical therapeutic scenario

Altaner

Altanerová²,

Cihova

et al. 2013

Intl Journal of Cancer

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“…Highly heterogenous nature of GBM is the cause of therapeutic resistance [17, 19]. These heterogenous tumoral tissues include approximately 1-3% of organizer cells in the cellular composition [16, 20].…”

Section: Discussionmentioning

confidence: 99%

Glioblastoma Stem Cells and Comparison of Isolation Methods

et al. 2019

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Background Glioblastoma (GBM) is the most aggressive and the most common primary brain tumor. Over the last few years, studies have identified many genetical and phenotypical molecular situations for developing new treatment modalities in patients with GBM. Nevertheless, main problem for the GBM is radio-chemotherapy resistance and relapse after the surgery. The identification of glioma stem cells and microenvironmental influences has created a paradigm shift in targets of therapy. Current studies have shown that glioma stem cell is responsible for aggressiveness, recurrence and resistance to therapy of GBM. GBM stem cell isolated from human GBM multiforme fresh tissue samples is important both for curative therapeutic options and personalized targeted therapy. The purpose of this study was to determine the most suitable isolation method of GBM stem cells (GSCs). Methods Tumor tissue sample was obtained during the surgical resection of lesion in patients with the diagnosis of GBM. Tumor stem cell isolation from tissue was performed in three different ways: 1) GBM cell isolation with trypsin; 2) GBM cell isolation with brain tumor dissociation Kit (BTD Kit); and 3) GBM cell isolation with tumor dissociation enzyme (TDE). Results We showed that GSCs were isolated from tumor specimen using flow cytometry and immunofluorescence staining. Our study showed that isolation with BTD Kit is the most suitable method to isolate GBM tissue-derived glial tumor stem cells. Conclusions The development of alternative personalized therapies targeting brain tumor stem cell is urgently needed. It is important to understand the fundamental mechanisms of driving stem cells. If their life cycle mechanisms can be identified, we can control the growth of GBM.

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“…Glioblastoma has a polyclonal nature and is composed of dividing tumor cells, tumor initiating cells and stromal cells [1, 2]. Glioblastoma initiating cells, also called cancer stem cells (CSCs), are characterized as a CD133 + cell population within a tumor that possess the abilities to self-renew, generate neurospheres in vitro and reproduce the original tumor when administered in vivo to immunocompromised animals [3, 4, 5, 6, 7].…”

Section: Introductionmentioning

confidence: 99%

“…It is unclear whether the CD133 + glioblastoma-initiating cells are derived from transformed progenitor cells or whether the heterogeneity of glioblastoma cells results in activation of genes that elicit mesenchymal properties and contribute to the formation of the tumor stroma, which is essential for the growth and maintenance of glioblastomas [2, 25]. Secreted factors from all cells present in the tumor mass are able to diffuse through the peritumoral stroma, thereby creating a permissive microenvironment for malignant progression [26, 27].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell-like properties of CD133+ glioblastoma initiating cells

et al. 2016

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Glioblastoma is composed of dividing tumor cells, stromal cells and tumor initiating CD133+ cells. Recent reports have discussed the origin of the glioblastoma CD133+ cells and their function in the tumor microenvironment. The present work sought to investigate the multipotent and mesenchymal properties of primary highly purified human CD133+ glioblastoma-initiating cells. To accomplish this aim, we used the following approaches: i) generation of tumor subspheres of CD133+ selected cells from primary cell cultures of glioblastoma; ii) analysis of the expression of pluripotency stem cell markers and mesenchymal stem cell (MSC) markers in the CD133+ glioblastoma-initiating cells; iii) side-by-side ultrastructural characterization of the CD133+ glioblastoma cells, MSC and CD133+ hematopoietic stem cells isolated from human umbilical cord blood (UCB); iv) assessment of adipogenic differentiation of CD133+ glioblastoma cells to test their MSC-like in vitro differentiation ability; and v) use of an orthotopic glioblastoma xenograft model in the absence of immune suppression. We found that the CD133+ glioblastoma cells expressed both the pluripotency stem cell markers (Nanog, Mush-1 and SSEA-3) and MSC markers. In addition, the CD133+ cells were able to differentiate into adipocyte-like cells. Transmission electron microscopy (TEM) demonstrated that the CD133+ glioblastoma-initiating cells had ultrastructural features similar to those of undifferentiated MSCs. In addition, when administered in vivo to non-immunocompromised animals, the CD133+ cells were also able to mimic the phenotype of the original patient's tumor. In summary, we showed that the CD133+ glioblastoma cells express molecular signatures of MSCs, neural stem cells and pluripotent stem cells, thus possibly enabling differentiation into both neural and mesodermal cell types.

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Glioma cancer stem cells and their role in therapy

Cited by 3 publications

References 61 publications

Complete regression of glioblastoma by mesenchymal stem cells mediated prodrug gene therapy simulating clinical therapeutic scenario

Complete regression of glioblastoma by mesenchymal stem cells mediated prodrug gene therapy simulating clinical therapeutic scenario

Glioblastoma Stem Cells and Comparison of Isolation Methods

Mesenchymal stem cell-like properties of CD133+ glioblastoma initiating cells

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