Decoding the role of extracellular vesicles in liver diseases

Deng, Fengyan; Magee, Nancy; Zhang, Yuxia

doi:10.1016/j.livres.2017.11.003

Cited by 22 publications

(31 citation statements)

References 103 publications

(146 reference statements)

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“…EVs have recently attracted considerable attention as an ideal miRNA delivery platform for therapeutic intervention of liver disorders, including hepatocellular carcinoma, due to their extremely low immunogenicity and toxicity profiles and to their ability to increase miRNAs stability in circulation [11,62]. In particular, transfer of miRNA by EVs isolated from mesenchymal cells have been shown to reduce liver fibrosis, promote hepatic regeneration after partial hepatectomy, modulate inflammatory response, and promote anti-tumor activity against hepatocellular carcinoma [4,63].…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles–Encapsulated MicroRNA-125b Produced in Genetically Modified Mesenchymal Stromal Cells Inhibits Hepatocellular Carcinoma Cell Proliferation

Baldari

Rocco

Magenta

et al. 2019

Cells

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Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and one of the prominent causes of cancer mortality, leading to approximately 780,000 deaths per year worldwide. Down-regulation of microRNA-125b (miR-125b) is a prognostic indicator in HCC patients. Conversely, over-expression of miR-125b in HCC cells induces cell cycle arrest, inhibits proliferation, migration and invasion. Extracellular vesicles (EVs) function as intercellular messengers transferring proteins, RNAs, DNAs, carbohydrates, and lipids. Since EVs protect their cargo from degradation, delivery of therapeutic bioactive molecules, in particular miRNAs, through EVs represents an innovative avenue for cancer therapy. In this study, we evaluated a replacement strategy for the treatment of HCC via delivery of EVs secreted from human adipose tissue-derived mesenchymal stromal/medicinal signaling cells (ASCs) genetically modified with a lentiviral vector expressing miR-125b with a specific ExoMotif sequence tag to enhance the loading into extracellular vesicles. In particular, we determined that the delivery of miR-125b-loaded EVs produced in engineered ASCs specifically reduces HCC cell proliferation in vitro modulating a series of miR-125b targets, which belong to the p53 signaling pathway. This proof-of-concept study supports the development of innovative therapeutic strategies for HCC via EV-mediated miRNA delivery.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles–Encapsulated MicroRNA-125b Produced in Genetically Modified Mesenchymal Stromal Cells Inhibits Hepatocellular Carcinoma Cell Proliferation

Baldari

Rocco

Magenta

et al. 2019

Cells

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“…While NPs mainly comprises of liposomes, polymeric NPs, and organic or inorganic NPs, EVs are biologically formed membrane-derived vesicles that carry multiple bioactive molecules to regulate cellular responses [41,42]. NPs and EVs can both be selectively engineered for the delivery of several therapeutics including miRNA/siRNA, proteins/peptides, and small-molecule inhibitors to target hepatic macrophages for the treatment of liver diseases [43]. The major advantages of these delivery vehicles are improved stability, site-specific delivery, and thus increased pharmacokinetics of the encapsulated therapeutics [44].…”

Section: Therapeutic Targeting Of Hepatic Macrophagesmentioning

confidence: 99%

“…Gene expression is biologically regulated via RNA interference, wherein microRNAs (miRNAs) and small interfering RNAs (siRNAs) are fundamental. miRNAs and siRNAs are naturally occurring small non-coding RNA molecules composed of about 22 nucleotides that regulate gene expression via gene silencing at the posttranscriptional level [42,43]. New insights illustrate that miRNA and siRNA expression is specifically altered in nearly all liver diseases, suggesting the great involvement of dysregulation of these non-coding RNAs in liver pathology [45,46].…”

Section: Mirna/sirna-based Approachesmentioning

confidence: 99%

Therapeutic Targeting of Hepatic Macrophages

Nijland

Bansal²

2020

Curr. Tissue Microenviron. Rep.

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Purpose of Review This review outlines the current knowledge about hepatic macrophages and provides an overview of therapeutic approaches to target hepatic macrophages for the treatment of liver diseases. Recent Findings In recent years, it has been increasingly recognized that hepatic macrophages (resident macrophages, Kupffer cells, or circulating bone marrow monocyte-derived macrophages) are implicated in liver homeostasis as well as in disease progression and resolution. More recently, different populations of hepatic macrophages with distinct phenotypes and functions have been identified that have shown to play distinct roles in the pathogenesis of various acute and chronic liver diseases. The understanding of the role of hepatic macrophages in initiation, progression, and resolution of liver diseases has given rise to the development of therapeutics that can target different phenotypes of hepatic macrophages. Innovative strategies comprises of microRNA (miRNA), small interfering RNA (siRNA), therapeutic proteins, and small-molecule inhibitors. Summary Evidence from recent in vitro and in vivo studies support the fact that hepatic macrophages can be efficiently targeted using miRNA/siRNA-based approaches, protein-based approaches, and small-molecule inhibitors for the treatment of liver diseases. However, more in-depth understanding underlying the roles of distinct macrophage phenotypes in different liver diseases is required for the translation of novel targeted therapeutics to the clinic. Keywords Hepatic macrophages. Targeted therapeutics. Liver diseases. Monocytes. Kupffer cells This article is part of the Topical Collection on Chronic Liver Disease

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“…Studies using stem cell-derived EVs have demonstrated that exosomes, per se, are a novel therapeutic target for diseases [26,27]. Thus, MSC-derived EVs have been identified as an important therapeutic target for liver disease, to protect against acute tubular injury, and to reduce myocardial ischemia/perfusion damage [26,28,29].…”

Section: Introductionmentioning

confidence: 99%

“…It has been described that there is an increase of circulating vesicles from liver origin after acute liver damage [33] and also in chronic liver conditions [34]. In addition, studies in relation to pathogenesis of different liver diseases have demonstrated implication of aberrant biogenesis of EVs [28].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Nano-Machines: Extracellular Vesicles Containing Active Enzymes and Their Contribution to Liver Diseases

2019

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Purpose of Review The field of extracellular vesicles is growing exponentially because of the important role that these extracellular organelles had on cell to cell communication, triggering a large number of review compilations focusing on different aspects of their biology. Although their importance as effectors or potential biomarkers is well covered, the highlight of extracellular vesicles as carriers of active enzymes which have the capability to transform the surrounding media is less covered by bibliographic studies. In the present review, we focus our attention on enzymatic activity carried by vesicles, with special attention on their contribution to liver conditions. Recent Findings Extracellular vesicles are circulating membrane-bound entities, characterized by a specific cargo. This cargo depends on the parental cell and the stimulus that triggers their release. Interestingly, the cargo includes active enzymes which had the ability of transforming the extracellular environment. Among them, extracellular vesicles derived from hepatocytes harbor specific liver enzymes that may cause an impact in the surrounds and target cells. Summary In this review, we summarize different active enzymes described in extracellular vesicles and we focus on enzymatic activities associated to liver damage. Since their release increases under liver damage conditions, their activity impact could play a role in the pathogenesis of liver and liver-associated diseases. Numerous examples in different liver conditions provided evidence of the potential of extracellular vesicles as therapeutic targets.

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Decoding the role of extracellular vesicles in liver diseases

Cited by 22 publications

References 103 publications

Extracellular Vesicles–Encapsulated MicroRNA-125b Produced in Genetically Modified Mesenchymal Stromal Cells Inhibits Hepatocellular Carcinoma Cell Proliferation

Extracellular Vesicles–Encapsulated MicroRNA-125b Produced in Genetically Modified Mesenchymal Stromal Cells Inhibits Hepatocellular Carcinoma Cell Proliferation

Therapeutic Targeting of Hepatic Macrophages

Metabolic Nano-Machines: Extracellular Vesicles Containing Active Enzymes and Their Contribution to Liver Diseases

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