Brain‐Cortex Microglia‐Derived Exosomes: Nanoparticles for Glioma Therapy

Murgoci, Adriana-Natalia; Cizkova, Dasa; Majerová, Petra; Petrovová, Eva; Medvecký, Ľubomír; Fournier, Isabelle; Salzet, Michel

doi:10.1002/cphc.201701198

Cited by 45 publications

(39 citation statements)

References 35 publications

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“…Indeed, these results positioned the MScCM treatment on the level of cell based therapy, where similar beneficial outcomes were observed [ 15 , 20 ]. The next step of this project will be isolation of the microvesicles (exosomes) from the MScCM as novel therapeutic agents as we recently demonstrated for microglia cells [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Localized Intrathecal Delivery of Mesenchymal Stromal Cells Conditioned Medium Improves Functional Recovery in a Rat Model of Spinal Cord Injury

Cizkova

Cubinkova

Smolek

et al. 2018

IJMS

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It was recently shown that the conditioned medium (CM) of mesenchymal stem cells can enhance viability of neural and glial cell populations. In the present study, we have investigated a cell-free approach via CM from rat bone marrow stromal cells (MScCM) applied intrathecally (IT) for spinal cord injury (SCI) recovery in adult rats. Functional in vitro test on dorsal root ganglion (DRG) primary cultures confirmed biological properties of collected MScCM for production of neurosphere-like structures and axon outgrowth. Afterwards, rats underwent SCI and were treated with IT delivery of MScCM or vehicle at postsurgical Days 1, 5, 9, and 13, and left to survive 10 weeks. Rats that received MScCM showed significantly higher motor function recovery, increase in spared spinal cord tissue, enhanced GAP-43 expression and attenuated inflammation in comparison with vehicle-treated rats. Spared tissue around the lesion site was infiltrated with GAP-43-labeled axons at four weeks that gradually decreased at 10 weeks. Finally, a cytokine array performed on spinal cord extracts after MScCM treatment revealed decreased levels of IL-2, IL-6 and TNFα when compared to vehicle group. In conclusion, our results suggest that molecular cocktail found in MScCM is favorable for final neuroregeneration after SCI.

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Section: Discussionmentioning

confidence: 99%

Localized Intrathecal Delivery of Mesenchymal Stromal Cells Conditioned Medium Improves Functional Recovery in a Rat Model of Spinal Cord Injury

Cizkova

Cubinkova

Smolek

et al. 2018

IJMS

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“…Taking into account the crosstalk between GAMs in glioma, it is also important to highlight that recent studies showed that microglia-derived exosomes in the brain could be used as nanotherapeutic agents against glioma cells ( Murgoci et al, 2018 ). In fact, extracellular ATP promotes microglia activation and induces the release of EVs, which can potentially mediate intercellular communication between microglia and the microenvironment ( Drago et al, 2017 ).…”

Section: Microglia and Astrocytes’ Role In Glioblastoma Malignancymentioning

confidence: 99%

Microglia/Astrocytes–Glioblastoma Crosstalk: Crucial Molecular Mechanisms and Microenvironmental Factors

Matias

Balça-Silva

Graça

et al. 2018

Front. Cell. Neurosci.

131

120

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In recent years, the functions of glial cells, namely, astrocytes and microglia, have gained prominence in several diseases of the central nervous system, especially in glioblastoma (GB), the most malignant primary brain tumor that leads to poor clinical outcomes. Studies showed that microglial cells or astrocytes play a critical role in promoting GB growth. Based on the recent findings, the complex network of the interaction between microglial/astrocytes cells and GB may constitute a potential therapeutic target to overcome tumor malignancy. In the present review, we summarize the most important mechanisms and functions of the molecular factors involved in the microglia or astrocytes–GB interactions, which is particularly the alterations that occur in the cell’s extracellular matrix and the cytoskeleton. We overview the cytokines, chemokines, neurotrophic, morphogenic, metabolic factors, and non-coding RNAs actions crucial to these interactions. We have also discussed the most recent studies regarding the mechanisms of transportation and communication between microglial/astrocytes – GB cells, namely through the ABC transporters or by extracellular vesicles. Lastly, we highlight the therapeutic challenges and improvements regarding the crosstalk between these glial cells and GB.

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“…283,284 It is reported that inhibition of NF-κB pathway activation is involved in breaking cellular redox homeostasis and triggers ROS production and accumulation through the JNK-mitogen-activated protein kinase (MAPK) axis. 285,286 Due to high specificity and the power to cross the BBB, exosome-and nanovesicle-mediated delivery [287][288][289] of peptides, [290][291][292][293] small molecules, miRNA, [294][295][296] and other drugs in Fig. 3 Steps of focal cerebral ischemia development…”

Section: Therapeutic Approaches For Ischemia and Gliomamentioning

confidence: 99%

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

Ghosh

Chakraborty

Sarkar

et al. 2019

Sig Transduct Target Ther

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Glioma and cerebral ischemic stroke are two major events that lead to patient death worldwide. Although these conditions have different physiological incidences,~10% of ischemic stroke patients develop cerebral cancer, especially glioma, in the postischemic stages. Additionally, the high proliferation, venous thrombosis and hypercoagulability of the glioma mass increase the significant risk of thromboembolism, including ischemic stroke. Surprisingly, these events share several common pathways, viz. hypoxia, cerebral inflammation, angiogenesis, etc., but the proper mechanism behind this co-occurrence has yet to be discovered. The hypercoagulability and presence of the D-dimer level in stroke are different in cancer patients than in the noncancerous population. Other factors such as atherosclerosis and coagulopathy involved in the pathogenesis of stroke are partially responsible for cancer, and the reverse is also partially true. Based on clinical and neurosurgical experience, the neuronal structures and functions in the brain and spine are observed to change after a progressive attack of ischemia that leads to hypoxia and atrophy. The major population of cancer cells cannot survive in an adverse ischemic environment that excludes cancer stem cells (CSCs). Cancer cells in stroke patients have already metastasized, but early-stage cancer patients also suffer stroke for multiple reasons. Therefore, stroke is an early manifestation of cancer. Stroke and cancer share many factors that result in an increased risk of stroke in cancer patients, and vice-versa. The intricate mechanisms for stroke with and without cancer are different. This review summarizes the current clinical reports, pathophysiology, probable causes of co-occurrence, prognoses, and treatment possibilities.

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Brain‐Cortex Microglia‐Derived Exosomes: Nanoparticles for Glioma Therapy

Cited by 45 publications

References 35 publications

Localized Intrathecal Delivery of Mesenchymal Stromal Cells Conditioned Medium Improves Functional Recovery in a Rat Model of Spinal Cord Injury

Localized Intrathecal Delivery of Mesenchymal Stromal Cells Conditioned Medium Improves Functional Recovery in a Rat Model of Spinal Cord Injury

Microglia/Astrocytes–Glioblastoma Crosstalk: Crucial Molecular Mechanisms and Microenvironmental Factors

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

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