Role of Extracellular Vesicles in Glioma Progression: Deciphering cellular biological processes to clinical applications

Author(s):  
Rashmi Rana ◽  
Shikha Joon ◽  
Kirti Chauhan ◽  
Vaishnavi Rathi ◽  
Nirmal Kumar Ganguly ◽  
...  

: Glioma predominantly targets glial cells in the brain and spinal cord. There are grade I, II, III, and IV gliomas with anaplastic astrocytoma and glioblastoma multiforme as the most severe forms of the disease. Current diagnostic methods are limited in their data acquisition and interpretation, markedly affecting treatment modalities and patient outcomes. Circulating extracellular vesicles (EVs) or “magic bullets” contain bioactive signature molecules such as DNA, RNA, proteins, lipids, and metabolites. These secretory “smart probes” participate in myriad cellular activities, including glioma progression. EVs are released by all cell populations and may serve as novel diagnostic biomarkers and efficient nanovehicles in the targeted delivery of encapsulated therapeutics. The present review describes the potential of EVbased biomarkers for glioma management.

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 902
Author(s):  
Eva Costanzi ◽  
Carolina Simioni ◽  
Gabriele Varano ◽  
Cinzia Brenna ◽  
Ilaria Conti ◽  
...  

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 767
Author(s):  
Courtney Davis ◽  
Sean I. Savitz ◽  
Nikunj Satani

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.


Author(s):  
Florian Puhm ◽  
Eric Boilard ◽  
Kellie R. Machlus

Extracellular vesicles (EVs) are a means of cell-to-cell communication and can facilitate the exchange of a broad array of molecules between adjacent or distant cells. Platelets are anucleate cells derived from megakaryocytes and are primarily known for their role in maintaining hemostasis and vascular integrity. Upon activation by a variety of agonists, platelets readily generate EVs, which were initially identified as procoagulant particles. However, as both platelets and their EVs are abundant in blood, the role of platelet EVs in hemostasis may be redundant. Moreover, findings have challenged the significance of platelet-derived EVs in coagulation. Looking beyond hemostasis, platelet EV cargo is incredibly diverse and can include lipids, proteins, nucleic acids, and organelles involved in numerous other biological processes. Furthermore, while platelets cannot cross tissue barriers, their EVs can enter lymph, bone marrow, and synovial fluid. This allows for the transfer of platelet-derived content to cellular recipients and organs inaccessible to platelets. This review highlights the importance of platelet-derived EVs in physiological and pathological conditions beyond hemostasis.


Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 371-380 ◽  
Author(s):  
Andrew M Shafik ◽  
Emily G Allen ◽  
Peng Jin

N6-methyladenosine (m6A) is a dynamic RNA modification that regulates various aspects of RNA metabolism and has been implicated in many biological processes and transitions. m6A is highly abundant in the brain; however, only recently has the role of m6A in brain development been a focus. The machinery that controls m6A is critically important for proper neurodevelopment, and the precise mechanisms by which m6A regulates these processes are starting to emerge. However, the role of m6A in neurodegenerative and neuropsychiatric diseases still requires much elucidation. This review discusses and summarizes the current body of knowledge surrounding the function of the m6A modification in regulating normal brain development, neurodegenerative diseases and outlines possible future directions.


2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Mahmood Mubasher ◽  
Aseel Sukik ◽  
Ahmed Hassan El Beltagi ◽  
Ali Rahil

A 23-year-old lady presented with vertigo and imbalance in walking, blurring of vision, diplopia, and headache, in addition to numbness in the lower limbs over a period of six days. On examination patient had nystagmus, ataxia, positive Romberg test, and hyperreflexia. MRI examination of the brain and spinal cord showed evidence of faint bright signal intensity foci in T2/FLAIR involving bilateral cerebral hemispheres, subcortical deep white matter, bilateral thalami, posterior pons and left brachium pontis, and basal ganglia, with small nodular enhancement that aligned along curvilinear structures; those lesions also were apparent along the spinal cord at multiple levels. The clinical and radiological features suggested CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) syndrome. Symptoms improved dramatically with high dose oral corticosteroids. Our report addresses the radiological and clinical pattern of a case of CLIPPERS rhombencephalitis, with added superior and inferior extension to involve the brain and spinal cord, which is to emphasize the importance of raising the awareness of this disease and the combined role of radiologist and physicians for the diagnosis of this potentially treatable entity, responsive to glucocorticosteroid immunosuppression.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Julianne Aebischer ◽  
Nathalie Bernard-Marissal ◽  
Brigitte Pettmann ◽  
Cédric Raoul

While studies on death receptors have long been restricted to immune cells, the last decade has provided a strong body of evidence for their implication in neuronal death and hence neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). ALS is a fatal paralytic disorder that primarily affects motoneurons in the brain and spinal cord. A neuroinflammatory process, associated with astrocyte and microglial activation as well as infiltration of immune cells, accompanies motoneuron degeneration and supports the contribution of non-cell-autonomous mechanisms in the disease. Hallmarks of Fas, TNFR, LT-βR, and p75NTR signaling have been observed in both animal models and ALS patients. This review summarizes to date knowledge of the role of death receptors in ALS and the link existing between the selective loss of motoneurons and neuroinflammation. It further suggests how this recent evidence could be included in an ultimate multiapproach to treat patients.


2016 ◽  
Vol 28 (2) ◽  
pp. 160
Author(s):  
V. Pirro ◽  
P. O. Favaron ◽  
C. R. Ferreira ◽  
L. S. Eberlin ◽  
R. S. Barreto ◽  
...  

Even though the role of lipids in pandemic diseases such as obesity and diabetes is a focus of increasing research, the role of lipids during organogenesis, when diverse diseases may be triggered, is unexplored. Also, pig embryonic tissues represent an attractive option for organ transplantation. This study introduces a detailed morphological analysis of swine fetal tissues with matching location of lipids acquired by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for the study of differential distribution of free fatty acids (FFA) and phospholipids (PL) in specific organs during fetal development. Samples from a pig fetuses around Day 50 of pregnancy were sectioned at a cryotome and mounted onto glass slides. Fixative agents were not used. DESI-MS images were run with a step size of 300 µm using a morphologically friendly (non-destructive) solvent combination, namely dimethylformamide/acetonitrile 1 : 1 (v/v). Data were acquired in the negative ion mode in the m/z range of 150 to 1000 from different sections representing the whole swine fetus body. Ion images were constructed using BioMAP software. After imaging, the whole-body tissue samples were stained with hematoxylin and eosin (H&E) and were overlaid to the DESI-MS lipid images. Differential distribution of FFA, phosphatidylcholines (PC), phosphatidylserines (PS), sulphatides (ST), and phosphatidylinositols (PI) was observed among organs, especially on nervous and circulatory systems, and digestive glands. Most lipids concentrated in the brain, spinal cord, and digestive glands such as the liver. For example, arachidonic acid was most abundant in neuronal tissue, whereas docosahexaenoic acid predominated in the liver and digestive glands. Distribution of PS (36 : 1) of m/z 788 was observed in all tissues except for the digestive system, but PS (40 : 6) of m/z 834.7 was exclusive of brain and spinal cord. Lipids related to brain and spinal cord were mostly polyunsaturated fatty acids as well as specific PS lipids. Arachidonic and eicosatrienoic acids are more concentrated in hindbrain and spinal cord, whereas PS was more abundant in the brain than in the spinal cord. There is no information on PS chemical composition during brain and spinal cord development, but PS concentration in the nervous tissue membranes varies with age, brain areas, cell type, and subcellular components. Several reports indicate that alteration in PS synthesis might participate in the mechanism of brain damage. Also, PS has been found to be altered in brain tumours. Oleic acid, fatty acid dimers, and the signalling lipid PI (38 : 3) were most significant for the digestive system and liver. Liver is one of the main organs involved in fatty acid metabolism (besides adipose tissue and muscle). By overlying morphological and molecular information, lipids seem to be a major player in the organogenesis process.


2018 ◽  
Vol 60 ◽  
pp. 38-51 ◽  
Author(s):  
Claudia Quezada ◽  
Ángelo Torres ◽  
Ignacio Niechi ◽  
Daniel Uribe ◽  
Susana Contreras-Duarte ◽  
...  

2020 ◽  
Vol 18 (2) ◽  
pp. 91-114
Author(s):  
Vladimir I. Vashchenko ◽  
Petr D. Shabanov

Extracellular vesicles (EVs) represent heterogeneous population of the microparticles liberated by almost all live cages which are widely investigated recently in various biological and medical areas. They usually consist of two basic types (exosomes and microvesicles) and recently draw the increasing attention in quality mesenges of the cellular alarm system. Really, these vesicles can influence on cages-recipients, transferring and delivering difficult complexes of biomolecules (the lipids, proteins, coagulation factors, antigene, nucleinic acids), protected from enzymatic to degradation in environment. Importance EVs has been shown in pathophysiology several bodies, in particular, in kidneys where various types of cages нефрона allocate EVs which mediate their communication with underlaying cages urinogenous ways. By numerous researches it is established that EVs are involved in cellular communications during the regenerative and pathological processes occurring in a kidney. During the last years also it has been proved that vesicles play an important role in normal physiology of kidneys. Though many mechanisms EVs at illnesses are still studied insufficiently, in particular, in kidneys, opening of a role of additional mechanisms can help to throw light on the biological processes proceeding in kidneys. Eventually, extracellular vesicles, allocated with nephritic cages, collect in urine, becoming, thus, the big resource as markers of illnesses urinogenous a path and the perspective noninvasive diagnostic tool at nephritic illnesses. In the present review we discuss the latest data about a role EVs in pathophysiology of kidneys and their potential prospects in diagnostics and therapy of nephritic illness.


Author(s):  
Eman Abbas ◽  
Mohamed A. Hassan ◽  
Godwin Sokpor ◽  
Kamila Kiszka ◽  
Linh Pham ◽  
...  

Oligodendrocytes are responsible for axon myelination in the brain and spinal cord. Generation of oligodendrocytes entails highly regulated multistage neurodevelopmental events, including proliferation, differentiation and maturation. The chromatin remodeling BAF (mSWI/SNF) complex is a notable regulator of neural development. In our previous studies, we determined the indispensability of the BAF complex scaffolding subunits BAF155 and BAF170 for neurogenesis, whereas their role in gliogenesis is unknown. Here, we show that the expression of BAF155 and BAF170 is essential for the genesis of oligodendrocytes during brain development. We report that the ablation of BAF155 and BAF170 in the dorsal telencephalic (dTel) neural progenitors or in oligodendrocyte-producing progenitors in the ventral telencephalon (vTel) in double-conditional knockout (dcKO) mouse mutants, perturbed the process of oligodendrogenesis. Molecular marker and cell cycle analyses revealed impairment of oligodendrocyte precursor specification and proliferation, as well as overt depletion of oligodendrocytes pool in dcKO mutants. Our findings unveil a central role of BAF155 and BAF170 in oligodendrogenesis, and thus substantiate the involvement of the BAF complex in the production of oligodendrocytes in the forebrain.


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