ORCID Profile
0000-0002-9201-0833
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Publisher: Wiley
Date: 02-2023
DOI: 10.1002/JEV2.12309
Abstract: Extracellular vesicles (EVs) are cell‐released, heterogenous nanoparticles that play important roles in (patho)physiological processes through intercellular communication. EVs are often depicted as having a single lipid bilayer, but many studies have demonstrated the existence of multilayered EVs. There has been minimal inquiry into differences between unilamellar and multilamellar EVs in terms of biogenesis mechanisms and functional effects. This commentary speculates on potential causes and roles of multilamellar EVs and serves as a call to action for the research community to unravel the complex layers of EVs.
Publisher: MDPI AG
Date: 22-12-2021
DOI: 10.3390/PHARMACEUTICS14010016
Abstract: Extracellular vesicles (EVs) are cell-released nanoparticles that transfer biomolecular content between cells. Among EV-associated biomolecules, microRNAs (miRNAs/miRs) represent one of the most important modulators of signaling pathways in recipient cells. Previous studies have shown that EVs from adipose-derived mesenchymal stromal cells (MSCs) and adipose tissue modulate inflammatory pathways in macrophages. In this study, the effects of miRNAs that are abundant in adipose tissue EVs and other biogenic nanoparticles (BiNPs) were assessed in terms of altering Toll-like receptor 4 (TLR4)-induced cytokines. TLR-4 signaling in macrophages is often triggered by pathogen or damage-induced inflammation and is associated with several diseases. This study demonstrates that miR-451a, which is abundant in adipose tissue BiNPs, suppresses pro-inflammatory cytokines and increases anti-inflammatory cytokines associated with the TLR4 pathway. Therefore, miR-451a may be partially responsible for immunomodulatory effects of adipose tissue-derived BiNPs.
Publisher: MDPI AG
Date: 22-08-2020
DOI: 10.3390/CELLS9091946
Abstract: Blood plasma is a readily accessible source of extracellular vesicles (EVs), i.e., cell-secreted nanosized carriers that contain various biomolecules, including glycans. Previous studies have demonstrated that glycans play a major role in physiological and pathological processes, and certain plasma glycans have been associated with disease conditions. However, glycome studies have been limited by a lack of analytical techniques with the throughput capacity necessary to study hundreds of clinical s les. This study is the first to characterize the EV plasma glycome based on all major glycan classes. The results based on glycan node analysis revealed, as expected, that plasma-derived EVs have distinct glycan features from donor-matched whole plasma. Specifically, glycan nodes corresponding to those observed in chondroitin sulfate, dermatan sulfate, type I keratan sulfate, and type II keratan sulfate were enriched on EVs. The identification of specific differences in glycan features in plasma vs. plasma-derived EVs is relevant for understanding the physiological role of EVs and as a reference for future diagnostic studies. Additionally, the results indicate that EV glycan nodes do not substantially differ among a small set of healthy donors. These results lay the framework for the further evaluation of all EV glycan classes as diagnostic markers, therapeutic targets, and biologically active components in health and disease.
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.NANO.2022.102515
Abstract: Monocyte-induced endothelial cell inflammation is associated with multiple pathological conditions, and extracellular vesicles (EVs) are essential nanosized components of intercellular communication. EVs derived from endotoxin-stimulated monocytes were previously shown to carry pro-inflammatory proteins and RNAs. The role of glucose transporter-1 (GLUT-1) and glycan features in monocyte-derived EV-induced endothelial cell inflammation remains largely unexplored. This study demonstrates that EVs derived from endotoxin-stimulated monocytes activate inflammatory pathways in endothelial cells, which are partially attributed to GLUT-1. Alterations in glycan features and increased levels of GLUT-1 were observed in EVs derived from endotoxin-stimulated monocytes. Notably, inhibition of EV-associated GLUT-1, through the use of fasentin, suppressed EV-induced inflammatory cytokines in recipient endothelial cells.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 2020
Publisher: Elsevier BV
Date: 12-2022
Publisher: MDPI AG
Date: 09-05-2023
DOI: 10.3390/IJMS24108506
Abstract: Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. Therefore, methods to comprehensively analyze all glyco-polymer classes on EVs are urgently needed. In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. The results indicate that GNA can identify EV-associated glyco-polymers that would remain undetected with conventional MS methods. Specifically, predictions based on GNA identified a GAG (hyaluronan) with varying abundance on EVs from two different melanoma cell lines. Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions.
Publisher: MDPI AG
Date: 13-04-2021
DOI: 10.3390/PH14040356
Abstract: Extracellular vesicles (EVs) mediate intercellular transport of biomolecular cargo in the body, making them promising delivery vehicles for bioactive compounds. Genetic engineering of producer cells has enabled encapsulation of therapeutic proteins in EVs. However, genetic engineering approaches can be expensive, time-consuming, and incompatible with certain EV sources, such as human plasma and bovine milk. The goal of this study was to develop a quick, versatile, and simple method for loading proteins in EVs post-isolation. Proteins, including CRISPR associated protein 9 (Cas9), were bound to cationic lipids that were further complexed with MDA-MB-231 cell-derived EVs through passive incubation. Size-exclusion chromatography was used to remove components that were not complexed with EVs. The ability of EVs to mediate intracellular delivery of proteins was compared to conventional methods, such as electroporation and commercial protein transfection reagents. The results indicate that EVs retain native features following protein-loading and obtain similar levels of intracellular protein delivery as conventional methods, but display less toxicity. This method opens up opportunities for rapid exploration of EVs for protein delivery.
Publisher: Ivyspring International Publisher
Date: 2019
DOI: 10.7150/THNO.37097
Publisher: Springer Science and Business Media LLC
Date: 07-11-2020
DOI: 10.1186/S12951-020-00722-2
Abstract: Cancer cell-derived extracellular vesicles (EVs) have previously been shown to contribute to pre-metastatic niche formation. Specifically, aggressive tumors secrete pro-metastatic EVs that travel in the circulation to distant organs to modulate the microenvironment for future metastatic spread. Previous studies have focused on the interface between pro-metastatic EVs and epithelial/endothelial cells in the pre-metastatic niche. However, EV interactions with circulating components such as low-density lipoprotein (LDL) have been overlooked. This study demonstrates that EVs derived from brain metastases cells (Br-EVs) and corresponding regular cancer cells (Reg-EVs) display different interactions with LDL. Specifically, Br-EVs trigger LDL aggregation, and the presence of LDL accelerates Br-EV uptake by monocytes, which are key components in the brain metastatic niche. Collectively, these data are the first to demonstrate that pro-metastatic EVs display distinct interactions with LDL, which impacts monocyte internalization of EVs.
Publisher: Wiley
Date: 18-02-2020
Location: United States of America
No related grants have been discovered for Sierra Walker.