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Extracellular vesicles (EVs) are naturally released membrane vesicles that act as carriers of proteins and RNAs for intercellular communication. With various biomolecules and specific ligands, EV has represented a novel form of information transfer, which possesses extremely outstanding efficiency and specificity compared to the classical signal transduction. In addition, EV has extended the concept of signal transduction to intercellular aspect by working as the collection of extracellular information. Therefore, the functions of EVs have been extensively characterized and EVs exhibit an exciting prospect for clinical applications. However, the biogenesis of EVs and, in particular, the regulation of this process by extracellular signals, which are essential to conduct further studies and support optimal utility, remain unclear. Here, we review the current understanding of the biogenesis of EVs, focus on the regulation of this process by extracellular signals and discuss their therapeutic value.
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Extracellular Vesicles/metabolism , Biological Transport , RNA/metabolism , Signal Transduction , Cell Communication/physiologyABSTRACT
Extracellular vesicles (EVs) with a variety of bioactive molecules can be continuously secreted during the storage of blood components, which can promote cell-cell interaction and mediate cell-to-cell signal transmission. EVs are widely involved in inflammation, metabolism and immunization. In recent years, studies have reported that EVs in the blood components can not only cause transfusion-related lung injury through activating neutrophils, but also act on monocytes to stimulate inflammatory response. EVs can play different regulatory effects on the immune system of patients. In this review, the role and mechanism in transfusion-related immunomodulation (TRIM) of EVs in different blood components have been summarized.
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Objective To study the protective effects and preliminary mechanisms of endothelial progenitor cells-derived microvesicles (EPC-MVs) on hypoxic-ischemic brain damage (HIBD) in newborn rats by using the HIBD model.Method Rat endothelial progenitor cells (EPCs) were cultured and microvesicles were extracted from EPCs culture medium by ultracentrifugation.A total of 60 neonatal SD rats were randomly assigned into control group,HIBD group,saline group and EPC-MVs group.The HIBD model was prepared in HIBD group,saline group and EPC-MVs group.After the preparation of the HIBD model,rats in saline group and EPC-MVs group received intraventricular injection with saline and EPC-MVs,respectively.After 72 hours,the rats were sacrificed for brain tissue,cerebral infarction was detected by TTC staining,vascular endothelial growth factor (VEGF) mRNA was tested by real-time PCR,protein western blot was used to detect changes in VEGF protein expression.Result Cells extracted and cultured from the spleen of 12-week-old SD rats were confirmed as EPCs by morphology and flow cytometry.EPC-MVs isolated by high-speed centrifugation from EPCs culture supernatant met the morphological characteristics of microvesicles by transmission electron microscopy.The infarcted brain tissue was not detected in the control group.The cerebral infarction volume ratios of HIBD group,saline group and EPC-MVs group were (80.3 ± 6.3) ％,(77.9 ± 8.9) ％,(35.2 ± 7.7) ％,respectively.The infarct volume of EPC-MVs group was significantly lower than that of HIBD group and saline group (P ＜ 0.001).The expression of VEGF mRNA and protein in HIBD group,saline group and EPC-MVs group were higher than those in control group (P ＜0.001).Among them,EPC-MVs group had the most significant increase,compared with the other three experimental groups,and the difference was statistically significant (P ＜ 0.001).There was no significant difference between saline group and HIBD group in the expression of VEGF mRNA and protein (P ＞ 0.05).Conclusion Intraventricular injection of EPC-MVs can attenuate HIBD in neonatal rats,and the mechanism may be related to up-regulation of VEGF expression.
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Objective: To review the advances in utilizing paracrine effect of stem cells in knee osteoarthritis (OA) treatment. Methods: The researches in applying stem cells derived conditioned medium, extracellular matrix, exosomes, and microvesicles in knee OA treatment and cartilage repair were reviewed and analyzed. Results: The satisfying outcomes of using different products of stem cells paracrine effect in knee OA condition as well as cartilage defect is revealed in studies in vitro and in vivo. The mechanism including suppressing the intraarticular inflammation, the apoptosis of chondrocytes, and the degradation of cartilage matrix, while enhancing the synthesis of cartilage matrix, the differentiation of in-situ stem cells into chondrocytes and the migration to the affected area. The effectiveness can be further improved supplemented with the tissue engineering methods or gene modification. Conclusion: Compared with the traditional stem cell therapy, applying the products from paracrine effect of stem cells in knee OA treatment is more economical and safer, presenting great potential in clinical practice.
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Extracellular vesicles (EVs) are membrane-derived vesicles that mediate intercellular communications. As professional phagocytes, neutrophils also produce EVs in response to various inflammatory stimuli during inflammatory processes. Neutrophil-derived EVs can be categorized into 2 subtypes according to the mechanism of generation. Neutrophil-derived trails (NDTRs) are generated from migrating neutrophils. The uropods of neutrophils are elongated by adhesion to endothelial cells, and small parts of the uropods are detached, leaving submicrometer-sized NDTRs. Neutrophil-derived microvesicles (NDMVs) are generated from neutrophils which arrived at the inflammatory foci. Membrane blebbing occurs in response to various stimuli at the inflammatory foci, and small parts of the blebs are detached from the neutrophils, leaving NDMVs. These 2 subtypes of neutrophil-derived EVs share common features such as membrane components, receptors, and ligands. However, there are substantial differences between these 2 neutrophil-derived EVs. NDTRs exert pro-inflammatory functions by guiding subsequent immune cells through the inflammatory foci. On the other hand, NDMVs exert anti-inflammatory functions by limiting the excessive immune responses of nearby cells. This review outlines the current understanding of the different subtypes of neutrophil-derived EVs and provides insights into the clinical relevance of neutrophil-derived EVs.
Subject(s)
Blister , Endothelial Cells , Extracellular Vesicles , Hand , Ligands , Membranes , Neutrophils , PhagocytesABSTRACT
Microvesicles (MVs, also known as microparticles) are small vesicles that originate from plasma membrane of almost all eukaryotic cells during apoptosis or activation. MVs can serve as extracellular vehicles to transport bioactive molecules from their parental cells to recipient target cells, thereby serving as novel mediators for intercellular communication. Importantly, more and more evidence indicates that MVs could play important roles in early pathogenesis and subsequent progression of cardiovascular and metabolic diseases. Elevated plasma concentrations of MVs, originating from red blood cells, leukocytes, platelets, or other organs and tissues, have been reported in various cardiometabolic diseases. Circulating MVs could serve as potential biomarkers for disease diagnosis or therapeutic monitoring. In this review, we summarized recently-published studies in the field and discussed the role of MVs in the pathogenesis of cardiometabolic diseases. The emerging values of MVs that serve as biomarker for non-invasive diagnosis and prognosis, as well as their roles as novel therapeutic targets in cardiometabolic diseases, were also described.
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Humans , Biomarkers , Metabolism , Cardiovascular Diseases , Blood , Diagnosis , Therapeutics , Cell Communication , Cell-Derived Microparticles , Metabolism , Metabolic Diseases , Blood , Diagnosis , TherapeuticsABSTRACT
Acute respiratory distress syndrome (ARDS) is a serious state threaten human health with a high mortality about 30%-40%. At present, there is no effective treatment for ARDS. Microvesicles derived from mesenchymal stem cells (MSC-MVs) have a heterogeneous subcellular structure secreted by MSCs. It plays an important role in the repair of tissue and organ damage.Recent studies have shown that MSC-MVs, played an important role in repairing lung injury, may replace MSC for cell therapy. Therefore MSC-MVs may bring new hope for ARDS treatment.
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Objective To explore the role of pancreatic cancer-derived microvesicles (MV) and their enclosed microRNAs (miRNA) in the pathogenesis of pancreatic cancer induced diabetes mellitus (DM).Methods The supernatants of three pancreatic cancer cell lines SW1990, BxPC3 and PANC1 were collected, and MV were isolated with gradient centrifugation.The entrance of MV into pancreatic islet cell line MIN6 was proved by Western blot assay and fluorescence-label method.The miRNA-19a levels were measured in MV and MV-free supernatants of three pancreatic cancer cells lines.The three experimental groups were MIN6 cells separately treated by MV derive from SW1990, BxPC3 and PANC1, and untreated MIN6 cells were assigned to the control group.The miRNA-19a levels as well as changes of glucose stimulated insulin secretion (GSIS) were measured.Afterward, pre-miRNA-19a and anti-miRNA-19a were transfected into MIN6 cells by liposome, and the effects of them on GSIS were observed.Results CD63 and AGO2 as the protein markers of MV and the entrance of MV from pancreatic cancer into pancreatic islet cell line MIN6 were detected by Western blotting.The miRNA-19a levels in MV and MV-free supernatants of SW1990, BxPC3 and PANC1 were (132.7±16.0), (32.8±4.3), (78.4±8.9),(22.6±3.3), (63.3±12.0) and (23.3±3.3) pmol/L, respectively, and the differences were statistically significant (t=10.44, 10.12 and 5.56,all P＜0.01).Compared to the MIN6 control group, the miRNA-19a levels of MIN6 treated by MV from SW1990, BxPC3 and PANC1 significantly increased, and the 2-△△Ctvalue was 2.02 ± 0.50, 1.80 ± 0.41 and 2.11 ± 0.59, respectively, and the differences were statistically significant (t=2.97, 2.77, 2.84;all P＜0.05).Stimulated with high glucose, the GSIS of pancreatic islet cells treated by SW1990, BxPC3 and PANC1 in three groups decreased, which were (103.73±16.49), (141.17±11.26), and (138.24±13.97) ng · mg protein-1 · h-1 MV, respectively, and that of control group was (256.24 ± 33.05) ng · mg protein-1 · h-1.The differences were statistically significant (t=4.13, 3.30 and 3.29, all P＜0.05).Compared with control group, GSIS of pre-miRNA-19a treated MIN6 remarkably decreased, which was (126.17± 62.87) ng · mg protein-1 ·h-1 and (316.72±91.87) ng · mg protein-1 · h-1 , and the difference was statistically significant (t=2.97, P＜0.05).GSIS of MIN6 cells transfected with anti-miRNA-19a was higher than that of control group, which was (697.47±77.62) ng · mg protein 1 · h-1 and (355.33 ±84.77) ng · mg protein-1 ·h-1 , and the difference was statistically significant (t=-2.97,P＜0.05).Conclusion The entrance of MV derived from pancreatic cancer into pancreatic islet cell line MIN6 may cause the dysfunction of insulin secretion an important signaling molecules, miRNA-19a.
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MicroRNAs ( miRNAs) play an important role in regulating various life activities .It has been confirmed that circulat-ing miRNAs are new biomarkers for the diagnosis of many diseases and closely related with their occurrence and progression .In recent years, miRNAs are found to exist stably in blood and other body fluids in forms of being encapsulated in microvesicle or binding with proteins.Their origins, existence forms and functions have become a hotspot of research in this field .This article reviews the recent studies on the origin , existence form and function of circulating miRNAs associated with cardiovascular disease , aiming to provide some evidence for miRNAs as the biomarker and target of cardiovascular disease .
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Objective To investigate the circulating microRNAs carrier in pancreatic cancer.Methods Pancreatic cancer cell lines SW1990 and BxPC3 were routinely cultured and serum of 6 patients with pancreatic cancer and 6 healthy subjects (control group) were collected.Serum and pancreatic cancer cell line supernatant microvesicles (MV) were obtained by gradient centrifugation.The expression of Ago2,CD63 was detected by Western blotting,the expression of microRNA in microvesicle section and microvesicle-free section in serum was detected by using quantitative PCR method.Results The supernatant MV of pancreatic cancer cell lines expressed Ago2,CD63 protein,and these MV carried different microRNAs in different cell lines.In the serum of pancreatic cancer and control group,miR-20a,miR-21,miR-24,miR-25,miR-191,miR-483-5p were detected,but the quantity was relatively higher in MV section,and the expression of microRNAs in pancreatic cancer's MV was inconsistent with that of control group.The expression of miR-20a,miR-24,miR-191 in pancreatic cancer group was (2.93 ± 0.29),(2.73 ± 0.46),(2.39 ± 0.51) times as much as those in control group,and the difference between the two groups was statistically significant (F =75.97,25.80,12.94,P ＜ 0.05 or ＜ 0.01).Conclusions The main circulating microRNAs carrier in pancreatic cancer is microvesicle.
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We report 13 chromophobe renal cell carcinomas (10.8%) observed among 120 renal cell carcinomas in adults. The average age was 53 (range: 34-72) years old, and 6 were males and 7 females. The mean tumor size was 10 (range: 5-17) cm, mean nuclear grade 2.4, and mean Robson's stage was 1.9. There were two distinct histologic variants; typical variant (n=9) and eosinophilic variant (n=4). Both of them showed typical light microscopic features and positive reaction with Hale's colloidal iron and carbonic anhydrase II, a marker protein of intercalated cells of renal collecting ducts. A strong positive immunoreactivity for epithelial membrane antigen was noted in the cytoplasm in 12 of 13 tumors. Numerous microvesicles, 180~440 nm in diameter, were identified ultrastructurally. DNA aneuploidy was found in 3 out of 10 cases. Neither local recurrence nor metastasis have been identified during the following period of 4~144 (mean 48) months.