Designer Extracellular Vesicles Modulate Pro‐Neuronal Cell Responses and Improve Intracranial Retention

2022 ◽  
pp. 2100805
Author(s):  
Lilibeth Ortega‐Pineda ◽  
Alec Sunyecz ◽  
Ana I. Salazar‐Puerta ◽  
Maria Angelica Rincon‐Benavides ◽  
Diego Alzate‐Correa ◽  
...  
2013 ◽  
Vol 31 (8) ◽  
pp. 796-803 ◽  
Author(s):  
Takeshi Kanaumi ◽  
Ivan Milenkovic ◽  
Homa Adle‐Biassette ◽  
Eleonora Aronica ◽  
Gabor G. Kovacs

2019 ◽  
Vol 317 (5) ◽  
pp. G739-G749 ◽  
Author(s):  
Harmeet Malhi

Extracellular vesicles (EVs) are membrane-defined nanoparticles released by most cell types. The EVs released by cells may differ quantitatively and qualitatively from physiological states to disease states. There are several unique properties of EVs, including their proteins, lipids and nucleic acid cargoes, stability in circulation, and presence in biofluids, which make them a critical vector for cell-to-cell communication and impart utility as a biomarker. EVs may also serve as a vehicle for selective cargo secretion. Similarly, EV cargo may be selectively manipulated for targeted therapeutic delivery. In this review an overview is provided on the EV classification, biogenesis, and secretion pathways, which are conserved across cell types. Next, cargo characterization and effector cell responses are discussed in the context of nonalcoholic steatohepatitis, alcoholic hepatitis, and acetaminophen-induced liver injury. The review also discusses the potential biomarker and therapeutic uses of circulating EVs.


2019 ◽  
Vol 6 (23) ◽  
pp. 1802219 ◽  
Author(s):  
Jian Lu ◽  
Jing Wu ◽  
Feiting Xie ◽  
Jie Tian ◽  
Xinyi Tang ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chiara Beretta ◽  
Elisabeth Nikitidou ◽  
Linn Streubel-Gallasch ◽  
Martin Ingelsson ◽  
Dag Sehlin ◽  
...  

AbstractAlzheimer’s disease (AD) is characterized by a substantial loss of neurons and synapses throughout the brain. The exact mechanism behind the neurodegeneration is still unclear, but recent data suggests that spreading of amyloid-β (Aβ) pathology via extracellular vesicles (EVs) may contribute to disease progression. We have previously shown that an incomplete degradation of Aβ42 protofibrils by astrocytes results in the release of EVs containing neurotoxic Aβ. Here, we describe the cellular mechanisms behind EV-associated neurotoxicity in detail. EVs were isolated from untreated and Aβ42 protofibril exposed neuroglial co-cultures, consisting mainly of astrocytes. The EVs were added to cortical neurons for 2 or 4 days and the neurodegenerative processes were followed with immunocytochemistry, time-lapse imaging and transmission electron microscopy (TEM). Addition of EVs from Aβ42 protofibril exposed co-cultures resulted in synaptic loss, severe mitochondrial impairment and apoptosis. TEM analysis demonstrated that the EVs induced axonal swelling and vacuolization of the neuronal cell bodies. Interestingly, EV exposed neurons also displayed pathological lamellar bodies of cholesterol deposits in lysosomal compartments. Taken together, our data show that the secretion of EVs from Aβ exposed cells induces neuronal dysfunction in several ways, indicating a central role for EVs in the progression of Aβ-induced pathology.


2017 ◽  
Vol 198 (12) ◽  
pp. 4707-4715 ◽  
Author(s):  
Tomohiro Kanuma ◽  
Takuya Yamamoto ◽  
Kouji Kobiyama ◽  
Eiko Moriishi ◽  
Yuji Masuta ◽  
...  

Allergy ◽  
2012 ◽  
Vol 67 (10) ◽  
pp. 1271-1281 ◽  
Author(s):  
M.-R. Kim ◽  
S.-W. Hong ◽  
E.-B. Choi ◽  
W.-H. Lee ◽  
Y.-S. Kim ◽  
...  

2020 ◽  
Author(s):  
Hong Gao ◽  
Zhenlong Luo ◽  
Zhongmou Jin ◽  
Yudong Ji ◽  
Wei Ying

AbstractObesity induces an adaptive expansion of β cell mass and insulin secretion abnormality. Here, we explore a novel role of adipose tissue macrophages (ATMs) in mediating obesity-induced β cell function and proliferation through releasing miRNA-containing extracellular vesicles (EVs). ATM EVs derived from obese mice notably suppress insulin secretion in both in vivo and in vitro experiments, whereas there are more proliferating β cells in the islets treated with obese ATM EVs. Depletion of miRNAs blunts the ability of obese ATM EVs to regulate β cell responses. miR-155, a highly enriched miRNA within obese ATM EVs, exerts profound regulation on β cell functions, as evidenced by impaired insulin secretion and increased β cell proliferation after miR-155 overexpression in β cells. By contrast, knockout of miR-155 can attenuate the regulation of obese ATM EVs on β cell responses. We further demonstrate that the miR-155-Mafb axis plays a critical role in controlling β cell responses. Taken together, these studies show a novel mechanism by which ATM-derived EVs act as endocrine cargoes delivering miRNAs and subsequently mediating β cell adaptation and functional dysfunction in obesity.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Malgorzata Czystowska-Kuzmicz ◽  
Anna Sosnowska ◽  
Dominika Nowis ◽  
Kavita Ramji ◽  
Marta Szajnik ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1266 ◽  
Author(s):  
Horrevorts ◽  
Stolk ◽  
Ven ◽  
Hulst ◽  
Hof ◽  
...  

Tumors that lack T cell infiltration are less likely to respond to immune checkpoint inhibition and could benefit from cancer vaccination for the initiation of anti-tumor T cell responses. An attractive vaccine strategy is in vivo targeting of dendritic cells (DCs), key initiators of antigen-specific T cell responses. In this study we generated tumor-derived apoptotic extracellular vesicles (ApoEVs), which are potentially an abundant source of tumor-specific neo-antigens and other tumor-associated antigens (TAAs), and which can be manipulated to express DC-targeting ligands for efficient antigen delivery. Our data demonstrates that by specifically modifying the glycocalyx of tumor cells, high-mannose glycans can be expressed on their cell surface and on extracellular vesicles derived after the induction of apoptosis. High-mannose glycans are the natural ligands of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), a dendritic cell associated C-type lectin receptor (CLR), which has the ability to efficiently internalize its cargo and direct it to both major histocompatibility complex (MHC)-I and MHC-II pathways for the induction of CD8+ and CD4+ T cell responses, respectively. Compared to unmodified ApoEVs, ApoEVs carrying DC-SIGN ligands are internalized to a higher extent, resulting in enhanced priming of tumor-specific CD8+ T cells. This approach thus presents a promising vaccination strategy in support of T cell-based immunotherapy of cancer.


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