Systemic Anticancer Neural Stem Cells in Combination with a Cardiac Glycoside for Glioblastoma Therapy

Teng, Jian; Hejazi, Seyedali; Badr, Christian E.; Tannous, Bakhos A.

doi:10.1002/stem.1727

Cited by 22 publications

(18 citation statements)

References 36 publications

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“…These engineered NSCs can track tumor cells and deliver sTRAIL to glioma cells in vivo , resulting in significant anti-tumor effects. Combinations of sTRAIL-secreting NSCs with anticancer drugs, including bortezomib (a proteasome inhibitor), PI-103 (a dual PI3K/mTOR inhibitor), and lanatoside C (a cardiac glycoside), resulted in synergistic therapeutic effects, emphasizing the potential clinical value of sensitizing glioma cells to TRAIL-induced NSC-mediated cell death (Hingtgen et al, 2010 ; Bagci-Onder et al, 2011 ; Balyasnikova et al, 2011 ; Teng et al, 2014 ). Importantly, studies with MSCs engineered to deliver sTRAIL showed equally promising results, as these cells efficiently tracked and successfully induced a caspase-dependent cell death in glioma cells, resulting in increased survival of glioma mice models (Shah et al, 2004 ; Menon et al, 2009 ; Sasportas et al, 2009 ; Choi et al, 2011 ).…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities

Salgado

Sousa

Costa

et al. 2015

Front. Cell. Neurosci.

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Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) share few characteristics apart from self-renewal and multipotency. In fact, the neurogenic and osteogenic stem cell niches derive from two distinct embryonary structures; while the later originates from the mesoderm, as all the connective tissues do, the first derives from the ectoderm. Therefore, it is highly unlikely that stem cells isolated from one niche could form terminally differentiated cells from the other. Additionally, these two niches are associated to tissues/systems (e.g., bone and central nervous system) that have markedly different needs and display diverse functions within the human body. Nevertheless they do share common features. For instance, the differentiation of both NSCs and MSCs is intimately associated with the bone morphogenetic protein family. Moreover, both NSCs and MSCs secrete a panel of common growth factors, such as nerve growth factor (NGF), glial derived neurotrophic factor (GDNF), and brain derived neurotrophic factor (BDNF), among others. But it is not the features they share but the interaction between them that seem most important, and worth exploring; namely, it has already been shown that there are mutually beneficially effects when these cell types are co-cultured in vitro. In fact the use of MSCs, and their secretome, become a strong candidate to be used as a therapeutic tool for CNS applications, namely by triggering the endogenous proliferation and differentiation of neural progenitors, among other mechanisms. Quite interestingly it was recently revealed that MSCs could be found in the human brain, in the vicinity of capillaries. In the present review we highlight how MSCs and NSCs in the neurogenic niches interact. Furthermore, we propose directions on this field and explore the future therapeutic possibilities that may arise from the combination/interaction of MSCs and NSCs.

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Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities

Salgado

Sousa

Costa

et al. 2015

Front. Cell. Neurosci.

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“…183 The use of mesenchymal stem cells in GBM has included delivery of gene therapy in murine 9,56 and canine 175 hosts, as well as delivery of synthetic miRNAs in vitro 98 and in a murine system. 115 Neural stem cells have been used to deliver lanatoside C in a murine host with a xenograft human GBM 151 and for delivery of carboxylesteraseactivated CPT-11 (irinotecan) therapy to xenograft human glioma;…”

Section: Stem Cell-mediated Delivery Of Therapiesmentioning

confidence: 99%

Novel delivery methods bypassing the blood-brain and blood-tumor barriers

Hendricks

Cohen-Gadol

Miller

2015

FOC

100

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Glioblastoma (GBM) is the most common primary brain tumor and carries a grave prognosis. Despite years of research investigating potentially new therapies for GBM, the median survival rate of individuals with this disease has remained fairly stagnant. Delivery of drugs to the tumor site is hampered by various barriers posed by the GBM pathological process and by the complex physiology of the blood-brain and blood–cerebrospinal fluid barriers. These anatomical and physiological barriers serve as a natural protection for the brain and preserve brain homeostasis, but they also have significantly limited the reach of intraparenchymal treatments in patients with GBM. In this article, the authors review the functional capabilities of the physical and physiological barriers that impede chemotherapy for GBM, with a specific focus on the pathological alterations of the blood-brain barrier (BBB) in this disease. They also provide an overview of current and future methods for circumventing these barriers in therapeutic interventions. Although ongoing research has yielded some potential options for future GBM therapies, delivery of chemotherapy medications across the BBB remains elusive and has limited the efficacy of these medications.

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“…Uniformity of key genes and epigenetic mechanisms that regulate life processes, commonality of immunocytochemical markers of cell surface (CD133+), identity of 63.5% proteins of proteomic profile [50] speak in favor of the hypothesis, according to which the CSCs of GBM come from neural SCs of the brain. Both types of SCs are capable for constant self-renewal, migration, high replication activity and multipotency [46,51,52].…”

Section: The Reasons For the Failures In The Mbt Therapy And Possiblementioning

confidence: 99%

Malignant Brain Tumors: Death Sentence, No Mercy

Bryukhovetskiy¹

2016

World. J. Oncol. Res.

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The article presents critical analysis of current methodological approaches, the standard and the options of complex therapy of malignant brain tumors (MBT). Author defines the main reasons for low effectiveness of MBT therapy. Relying on post-genome innovations (mass-spectrometry proteome mapping and whole transcriptome profiling of gene expression of cancer cells (CCs), cancer stem cells (CSCs) and tissue-specific stem cells (TSSCs) of the cancer patient, and their comparative analysis) the author proposes systemic solution for the MBT complex therapy that consists in a new alternative paradigm of cytoregulatory anti-cancer treatment of the MBT that is aimed at rigid control, management and regulation of the number of CCs and CSCs in the body. The goal of a new treatment paradigm is to transfer acute, uncontrollable and mortal process into chronic and non-lethal disease, and, thus, to improve survival rates and life quality of the patients. The instrument to implement the new paradigm is a sparing algorithm of conventional therapeutic methods and immune therapy, supplemented with personalized anti-tumor proteome-based cell therapy. The therapy implies transfusions of transcriptome-modified autologous TSSCs with specified properties to regulate the reproductive functions of the CSCs. The author proposes the complex therapy of the MBT and shows its social and economic significance for the society and neuroscience.

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Systemic Anticancer Neural Stem Cells in Combination with a Cardiac Glycoside for Glioblastoma Therapy

Cited by 22 publications

References 36 publications

Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities

Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities

Novel delivery methods bypassing the blood-brain and blood-tumor barriers

Malignant Brain Tumors: Death Sentence, No Mercy

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