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EV literature (RSS feed from PubMed)

Search terms: exosomes OR "extracellular vesicles" OR microvesicles OR microparticles. Direct link to the PubMed search here.

A microparticle platform for STING-targeted immunotherapy enhances natural killer cell- and CD8+ T cell-mediated anti-tumor immunity.

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A microparticle platform for STING-targeted immunotherapy enhances natural killer cell- and CD8+ T cell-mediated anti-tumor immunity.

Biomaterials. 2019 Mar 14;205:94-105

Authors: Watkins-Schulz R, Tiet P, Gallovic MD, Junkins RD, Batty C, Bachelder EM, Ainslie KM, Ting JPY

Abstract
Immunotherapies have significantly improved cancer patient survival, but response rates are still limited. Thus, novel formulations are needed to expand the breadth of immunotherapies. Pathogen associated molecular patterns (PAMPs) can be used to stimulate an immune response, but several pathogen recognition receptors are located within the cell, making delivery challenging. We have employed the biodegradable polymer acetalated dextran (Ace-DEX) to formulate PAMP microparticles (MPs) in order to enhance intracellular delivery. While treatment with four different PAMP MPs resulted in tumor growth inhibition, cyclic GMP-AMP (cGAMP) MPs were most effective. cGAMP MPs showed anti-tumor efficacy at doses 100-1000 fold lower than published doses of soluble cGAMP in two murine tumor models. Treatment with cGAMP MPs resulted in increased natural killer cell numbers in the tumor environment. Immune cell depletion studies confirmed that NK cells were responsible for the anti-tumor efficacy in an aggressive mouse melanoma model. NK cells and CD8+ T cells were both required for early anti-tumor function in a triple negative breast cancer model. In summary, cGAMP MP treatment results in NK and T cell-dependent anti-tumor immune response.

PMID: 30909112 [PubMed - as supplied by publisher]

High Level Extraction of Recyclable Nanocatalysts by using Polyphosphazenes Microparticles.

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High Level Extraction of Recyclable Nanocatalysts by using Polyphosphazenes Microparticles.

Langmuir. 2019 Mar 25;:

Authors: Dong Y, Chen S, Lu X, Lu Q

Abstract
Improper disposal of metal nanoparticles has caused serious environmental and pathological problems due to their active nanotoxicity. Therefore, there is an urgent need to develop a strategy for efficiently removing redundant metal nanoparticles from water, while also permitting restoration of their catalytic activities to those of pristine particles for reapplication. Herein, we present intrinsically nitrogen-rich crosslinked polyphosphazene microparticles to capture silver nanoparticles (AgNPs) from aqueous media by a simple one-step method. The described microparticles exhibit an outstanding adsorption capacity for AgNPs of approximately 59.45 mg/g, exceeding those of other adsorbents. The adsorption kinetics of AgNPs on these microparticles obeyed a pseudo-second-order kinetic model. More importantly, the recovered AgNPs maintained good catalytic activity in the reduction of methylene blue by sodium borohydride. Based on their simple preparation, high adsorption efficiency, and non-destructive effect on the catalytic activity of the recovered AgNPs, the described polyphosphazene microparticles display promising potential for the removal and recovery of AgNPs from water.

PMID: 30908060 [PubMed - as supplied by publisher]

Effects of localization of antigen proteins in antigen-loaded exosomes on efficiency of antigen presentation.

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Effects of localization of antigen proteins in antigen-loaded exosomes on efficiency of antigen presentation.

Mol Pharm. 2019 Mar 25;:

Authors: Arima Y, Liu W, Takahashi Y, Nishikawa M, Takakura Y

Abstract
Exosomes are considered to be vehicles of antigen delivery. The localization of antigen proteins, i.e., whether they lie on the outer surface or inner surface of exosomes, might affect antigen presentation after exosomes are taken up by antigen-presenting cells; however, little is known about the importance of this phenomenon. In this study, lactadherin (LA) and group-specific antigen (Gag), exosome-tropic proteins that had previously been shown to cause the localization of luciferase to the outer surface and inner surface of exosomes, respectively (Takahashi et al. J Biotechnol. 2013; Charoenviriyakul et al. Mol Pharm. 2018), were used to examine the importance of the localization of antigen proteins in antigen presentation. Human embryonic kidney cells 293 (HEK293) were selected as exosomes producing cells. First, green fluorescent protein (GFP) was used to trace intracellular behavior of antigen proteins after uptake by murine dendritic DC2.4 cells. GFP-derived fluorescence signals were detected in cells only when GFP-inner-loaded (Gag-GFP) exosomes were added to them. Then, ovalbumin (OVA) was used as a model antigen protein, and OVA-loaded exosomes were added to bone marrow-derived dendritic cells. OVA-inner-loaded (Gag-OVA) exosomes showed enhanced class I antigen presentation capacity as compared with that of OVA-outer-loaded (OVA-LA) exosomes. Using PKH-labeled exosomes, it was found that the localization of OVA had very little effect on the cellular uptake of exosomes. These results indicate that the loading of antigen proteins inside exosomes helps in efficient antigen presentation.

PMID: 30908053 [PubMed - as supplied by publisher]

Increased salivary microvesicles are associated with the prognosis of patients with oral squamous cell carcinoma.

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Increased salivary microvesicles are associated with the prognosis of patients with oral squamous cell carcinoma.

J Cell Mol Med. 2019 Mar 25;:

Authors: Zhong WQ, Ren JG, Xiong XP, Man QW, Zhang W, Gao L, Li C, Liu B, Sun ZJ, Jia J, Zhang WF, Zhao YF, Chen G

Abstract
Microvesicles (MVs), which are cell-derived membrane vesicles present in body fluids, are closely associated with the development of malignant tumours. Saliva, one of the most versatile body fluids, is an important source of MVs. However, the association between salivary MVs (SMVs) and oral squamous cell carcinoma (OSCC), which is directly immersed in the salivary milieu, remains unclear. SMVs from 65 patients with OSCC, 21 patients with oral ulcer (OU), and 42 healthy donors were purified, quantified and analysed for their correlations with the clinicopathologic features and prognosis of OSCC patients. The results showed that the level of SMVs was significantly elevated in patients with OSCC compared to healthy donors and OU patients. Meanwhile, the level of SMVs showed close correlations with the lymph node status, and the clinical stage of OSCC patients. Additionally, the ratio of apoptotic to non-apoptotic SMVs was significantly decreased in OSCC patients with higher pathological grade. Consistently, poorer overall survival was observed in patients with lower ratio of apoptotic to non-apoptotic SMVs. In conclusion, the elevated level of SMVs is associated with clinicopathologic features and decreased survival in patients with OSCC, suggesting that SMVs are a potential biomarker and/or regulator of the malignant progression of OSCC.

PMID: 30907490 [PubMed - as supplied by publisher]

Characterization of Serum Exosomes from a Transgenic Mouse Model of Alzheimer's Disease.

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Characterization of Serum Exosomes from a Transgenic Mouse Model of Alzheimer's Disease.

Curr Alzheimer Res. 2019 Mar 21;:

Authors: Rosas-Hernandez H, Cuevas E, Raymick JB, Robinson BL, Ali SF, Hanig J, Sarkar S

Abstract
BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia characterized by amyloid plaques containing amyloid beta (Aβ) peptides and neurofibrillary tangles containing tau protein. In addition to neuronal loss, cerebral amyloid angiopathy (CAA) commonly occurs in AD. CAA is characterized by Aβ deposition in brain microvessels. Recent studies have suggested that exosomes (cell-derived vesicles containing a diverse cargo) may be involved in the pathogenesis of AD.
OBJECTIVE: Isolate and characterize brain-derived exosomes from a transgenic mouse model of AD that presents CAA.
METHODS: Exosomes were isolated from serum obtained from 13-month-old wild type and AD transgenic female mice using an exosome precipitation solution. Characterization of exosomal proteins was performed by western blots and dot blots.
RESULTS: Serum exosomes were increased in transgenic mice compared to wild types as determined by increased levels of the exosome markers flotillin and alix. High levels of neuronal markers were found in exosomes, without difference between the 2 groups. Markers for endothelial-derived exosomes were decreased in the transgenic model, while astrocytic-derived exosomes were increased. Exosome characterization showed increased levels of oligomeric Aβ and oligomeric and monomeric forms tau on the transgenic animals. Levels of amyloid precursor protein were also increased. In addition, pathological and phosphorylated forms of tau were detected, but no difference was observed between groups.
CONCLUSION: These data suggest that monomeric and oligomeric forms Aβ and tau are secreted into serum via brain exosomes, most likely derived from astrocytes in the transgenic mouse model of AD with CAA. Studies on the implication of this event in the propagation of AD are underway.

PMID: 30907317 [PubMed - as supplied by publisher]

Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles.

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Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles.

Epigenetics. 2019 Mar 24;:1-13

Authors: Mannerström B, Kornilov R, Abu-Shahba AG, Chowdhury IM, Sinha S, Seppänen-Kaijansinkko R, Kaur S

Abstract
Extracellular vesicles (EVs) are central to intercellular communication and play an important role in cancer progression and development. Osteosarcoma (OS) is an aggressive bone tumour, characterized by the presence of malignant mesenchymal cells. The specific tumour-driving genetic alterations that are associated with OS development are currently poorly understood. Mesenchymal stem cells (MSCs) of osteogenic lineage have been postulated as likely candidates as the cells of origin for OS, thus indicating that MSCs and OS stroma cells may be related cell types. Therefore, this study set out to examine the EV-mediated intercellular crosstalk of MSCs and OS. MSCs and pre-osteoblasts were treated with OS-EVs at different time points, and the epigenetic signature of OS-EVs was assessed by methylation analysis of LINE-1 (long interspersed element) and tumour suppressor genes. In addition, surface markers and expression of specific genes were also evaluated. Our data indicated that OS-EVs mediated LINE-1 hypomethylation in MSCs, whereas an opposite effect was seen in pre-osteoblasts, indicating that MSCs but not pre-osteoblasts were susceptible to epigenetic transformation. Thus, OS-EVs modulated the fate of MSCs by modulating the epigenetic status, and also influenced the expression of genes related to bone microenvironment remodelling. Overall, this study provided evidence that epigenetic regulation appears to be an early event in the transformation of MSCs during the development of OS. Elucidating the mechanisms of EV-mediated communication may lead to new avenues for therapeutic exploitation.

PMID: 30907225 [PubMed - as supplied by publisher]

 

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