scholarly journals Crosstalk between tongue carcinoma cells, extracellular vesicles, and immune cells in in vitro and in vivo models

Oncotarget ◽  
2017 ◽  
Vol 8 (36) ◽  
pp. 60123-60134 ◽  
Author(s):  
Ahmed Al-Samadi ◽  
Shady Adnan Awad ◽  
Katja Tuomainen ◽  
Yue Zhao ◽  
Abdelhakim Salem ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Immune Cells ◽  
Carcinoma Cells ◽  
Tongue Carcinoma ◽  
In Vivo Models

scholarly journals Mesenchymal stem cells versus their extracellular vesicles in treatment of liver fibrosis: Is it possible to compare?

2021 ◽  
Vol 9 (2) ◽  
Author(s):  
Noha Attia ◽  
Yasmine Khalifa ◽  
Dina Rostom ◽  
Mohamed Mashal
Keyword(s):  
Liver Fibrosis ◽  
Extracellular Vesicles ◽  
Therapeutic Strategy ◽  
Secretory Proteins ◽  
Apoptotic Bodies ◽  
Limited Evidence ◽  
In Vivo Models ◽  
Dose Determination

Liver fibrosis (LF) is a worldwide health problem that is associated with a range of complications and high mortality. Due to the scarcity of liver donors, mesenchymal stem cell (MSC) therapy emerged as an alternative therapeutic strategy. However, it is widely accepted that most of the transplanted MSCs exhibit their therapeutic impact mainly via a bystander paracrine (medicinal) capacity. In addition to their secretory proteins, MSCs also produce various types of extracellular vesicles (EVs) that are classified into three main subtypes: microvesicles, exosomes and apoptotic bodies. Thanks to their peculiar cargo composition (e.g., proteins, lipids, and nucleic acids), EVs serve as an advantageous candidate for cell-free therapy. Recently, MSC-derived EVs (MSC-EVs) have gained the podium due to their regenerative and immunomodulatory effect. In mitigation/treatment of LF, a plethora of recent studies have shown the anti-inflammatory, anti-fibrotic and cytoprotective effects of both MSCs and MSC-EVs in various in vitro and in vivo models of LF. However, despite the limited evidence, we sought in this mini review to sort out the established data and formulate several challenging questions that must be answered to pave the way for further clinical applications. One of the major questions to ask is “Which is the best therapeutic approach, MSCs or MSC-EVs?” We tried to highlight how difficult it might be to compare the two approaches while our understanding of both candidates is still deficient. Among the major obstacles against such comparison is the inaccurate equivalent dose determination, the unknown in vivo behavior, and the undetermined lifespan/fate of each. Currently, the fields of MSCs and MSC-EVs seem to be rich in ideas but lacking in appropriate technologies to test these ideas. Nevertheless, continuous efforts are likely to help resolve some of the challenges listed here.

scholarly journals Extracellular Vesicles: Intercellular Communication Mediators in Antiphospholipid Syndrome

2021 ◽  
Author(s):  
Ula Štok ◽  
Saša Čučnik ◽  
Snežna Sodin-Šemrl ◽  
Polona Žigon
Keyword(s):  
Extracellular Vesicles ◽  
Antiphospholipid Syndrome ◽  
Intercellular Communication ◽  
Systemic Autoimmune Disease ◽  
In Vivo Models ◽  
Isolation And Characterization ◽  
Increased Risk ◽  
Insight Into

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis, obstetric complications and the presence of antiphospholipid antibodies (aPL) that cause endothelial injury and thrombophilia. Extracellular vesicles are involved in endothelial and thrombotic pathologies and may therefore have an influence on the prothrombotic status of APS patients. Intercellular communication and connectivity are important mechanisms of interaction between healthy and pathologically altered cells. Despite well-characterized in vitro and in vivo models of APS pathology, the field of extracellular vesicles is still largely unexplored and could therefore provide an insight into the APS mechanism and possibly serve as a biomarker to identify patients at increased risk. The analysis of EVs poses a challenge due to the lack of standardized technology for their isolation and characterization. Recent findings in the field of EVs offer promising aspects that may explain their role in the pathogenesis of various diseases, including APS.

scholarly journals In vitro and in vivo analysis of microvesicle-mediated metastasis using a bright, red-shifted bioluminescent reporter protein of extracellular vesicles

2021 ◽  
Author(s):  
Ahmed A Zarea ◽  
Gloria I Perez ◽  
David Broadbent ◽  
Benedikt Dolgikh ◽  
Matthew P Bernard ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mammary Carcinoma ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Carcinoma Cells ◽  
Reporter Protein ◽  
Mammary Carcinoma Cells ◽  
In Vivo Analysis

Cancer cells produce heterogeneous extracellular vesicles (EVs) as mediators of intercellular communication. Our study focused on a novel method to image EV subtypes and their biodistribution in vivo. Regardless of injection routes, we established that reporter EVs isolated from murine mammary carcinoma cells expressing PalmReNL, which utilizes bioluminescence resonance energy transfer (BRET), localized to the lungs. This new EV reporter allowed highly sensitive EV tracking in vitro and in vivo and enabled us to begin studies to understand the commonalities and functional differences of the EV subtypes. We demonstrated the early appearance of metastatic foci in the lungs of mammary tumor-bearing mice following multiple injections of the microvesicle (MV)-enriched fraction derived from mammary carcinoma cells. In addition, the results we present here show that tumor cell-derived MVs act on distant tissues through upregulating LC3 expression within the lung.

Extracellular vesicles derived from Malassezia furfur stimulate IL-6 production in keratinocytes as demonstrated in in vitro and in vivo models

2019 ◽  
Vol 93 (3) ◽  
pp. 168-175 ◽  
Author(s):  
Yu-Jing Zhang ◽  
Yang Han ◽  
Yu-Zhe Sun ◽  
Hang-Hang Jiang ◽  
Min Liu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Malassezia Furfur ◽  
In Vivo Models

Microvesiculation and Disease

2013 ◽  
Vol 41 (1) ◽  
pp. 237-240 ◽  
Author(s):  
Jameel M. Inal ◽  
Una Fairbrother ◽  
Sheelagh Heugh
Keyword(s):  
Infectious Disease ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
In Vivo Models ◽  
Cell Functions ◽  
Models Of Disease ◽  
New Treatments ◽  
Acute Myeloid

The important roles of extracellular vesicles in the pathogenesis of various diseases are rapidly being elucidated. As important vehicles of intercellular communication, extracellular vesicles, which comprise microvesicles and exosomes, are revealing important roles in cancer tumorigenesis and metastases and in the spread of infectious disease. The September 2012 Focused Meeting ‘Microvesiculation and Disease’ brought together researchers working on extracellular vesicles. The papers in this issue of Biochemical Society Transactions review work in areas including HIV infection, kidney disease, hypoxia-mediated tumorigenesis and down-regulation of immune cell functions in acute myeloid leukaemia by tumour-derived exosomes. In all cases, microvesicles and exosomes have been demonstrated to be important factors leading to the pathophysiology of disease or indeed as therapeutic vehicles in possible new treatments. The aim was, having enhanced our molecular understanding of the contribution of microvesicles and exosomes to disease in vitro, to begin to apply this knowledge to in vivo models of disease.

scholarly journals Enhancement of therapeutic potential of mesenchymal stem cell-derived extracellular vesicles

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyong-Su Park ◽  
Elga Bandeira ◽  
Ganesh V. Shelke ◽  
Cecilia Lässer ◽  
Jan Lötvall
Keyword(s):  
Cell Therapy ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Therapeutic Effects ◽  
In Vivo Models ◽  
Secreted Factors ◽  
Associated Proteins

Abstract After the initial investigations into applications of mesenchymal stem cells (MSCs) for cell therapy, there was increased interest in their secreted soluble factors. Following studies of MSCs and their secreted factors, extracellular vesicles (EVs) released from MSCs have emerged as a new mode of intercellular crosstalk. MSC-derived EVs have been identified as essential signaling mediators under both physiological and pathological conditions, and they appear to be responsible for many of the therapeutic effects of MSCs. In several in vitro and in vivo models, EVs have been observed to have supportive functions in modulating the immune system, mainly mediated by EV-associated proteins and nucleic acids. Moreover, stimulation of MSCs with biophysical or biochemical cues, including EVs from other cells, has been shown to influence the contents and biological activities of subsequent MSC-derived EVs. This review provides on overview of the contents of MSC-derived EVs in terms of their supportive effects, and it provides different perspectives on the manipulation of MSCs to improve the secretion of EVs and subsequent EV-mediated activities. In this review, we discuss the possibilities for manipulating MSCs for EV-based cell therapy and for using EVs to affect the expression of elements of interest in MSCs. In this way, we provide a clear perspective on the state of the art of EVs in cell therapy focusing on MSCs, and we raise pertinent questions and suggestions for knowledge gaps to be filled.

scholarly journals Renal Regenerative Potential of Extracellular Vesicles Derived from miRNA-Engineered Mesenchymal Stromal Cells

2019 ◽  
Vol 20 (10) ◽  
pp. 2381 ◽  
Author(s):  
Marta Tapparo ◽  
Stefania Bruno ◽  
Federica Collino ◽  
Gabriele Togliatto ◽  
Maria Chiara Deregibus ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Interventions ◽  
In Vivo Models ◽  
Regenerative Effect ◽  
In Vivo Experiments ◽  
Renal Regeneration

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) possess pro-regenerative potential in different animal models with renal injury. EVs contain different molecules, including proteins, lipids and nucleic acids. Among the shuttled molecules, miRNAs have a relevant role in the pro-regenerative effects of EVs and are a promising target for therapeutic interventions. The aim of this study was to increase the content of specific miRNAs in EVs that are known to be involved in the pro-regenerative effect of EVs, and to assess the capacity of modified EVs to contribute to renal regeneration in in vivo models with acute kidney injuries. To this purpose, MSCs were transiently transfected with specific miRNA mimics by electroporation. Molecular analyses showed that, after transfection, MSCs and derived EVs were efficiently enriched in the selected miRNAs. In vitro and in vivo experiments indicated that EVs engineered with miRNAs maintained their pro-regenerative effects. Of relevance, engineered EVs were more effective than EVs derived from naïve MSCs when used at suboptimal doses. This suggests the potential use of a low amount of EVs (82.5 × 106) to obtain the renal regenerative effect.

scholarly journals Circulating extracellular vesicles from individuals at high-risk of lung cancer induce pro-tumorigenic conversion of stromal cells through transfer of miR-126 and miR-320

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Francesca Pontis ◽  
Luca Roz ◽  
Mavis Mensah ◽  
Miriam Segale ◽  
Massimo Moro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Endothelial Cells ◽  
High Risk ◽  
Cancer Patients ◽  
Extracellular Vesicles ◽  
In Vivo Models ◽  
Lung Cancer Patients

Abstract Background Extracellular vesicles (EVs) containing specific subsets of functional biomolecules are released by all cell types and analysis of circulating EVs can provide diagnostic and prognostic information. To date, little is known regarding the role of EVs both as biomarkers and potential key players in human lung cancer. Methods Plasma EVs were isolated from 40 cancer-free heavy-smokers classified according to a validated 24-microRNA signature classifier (MSC) at high (MSCpos-EVs) or low (MSCneg-EVs) risk to develop lung cancer. EVs origin and functional properties were investigated using in vitro 3D cultures and in vivo models. The prognostic value of miRNAs inside EVs was assessed in training and in validation cohorts of 54 and 48 lung cancer patients, respectively. Results Different membrane composition, biological cargo and pro-tumorigenic activity were observed in MSCpos vs MSCneg-EVs. Mechanistically, in vitro and in vivo results showed that miR-126 and miR-320 from MSCpos-EVs increased pro-angiogenic phenotype of endothelial cells and M2 polarization of macrophage, respectively. MSCpos-EVs prompted 3D proliferation of non-tumorigenic epithelial cells through c-Myc transfer. Moreover, hypoxia was shown to stimulate the secretion of EVs containing c-Myc from fibroblasts, miR-126-EVs from endothelial cells and miR-320-EVs from granulocytes. Lung cancer patients with higher levels of mir-320 into EVs displayed a significantly shorter overall survival in training [HR2.96] and validation sets [HR2.68]. Conclusion Overall our data provide a new perspective on the pro-tumorigenic role of circulating EVs in high risk smokers and highlight the significance of miR-320-EVs as a new prognostic biomarker in lung cancer patients.

scholarly journals Role of the Exosome Secretion Machinery in Ovarian Carcinoma: In Vitro and In Vivo Models

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Esther Channah Broner ◽  
Hadil Onallah ◽  
Tali Tavor Re’em ◽  
Ben Davidson ◽  
Reuven Reich
Keyword(s):  
Ovarian Carcinoma ◽  
Mrna Expression ◽  
Carcinoma Cells ◽  
Serous Carcinoma ◽  
Clinical Role ◽  
In Vivo Models ◽  
Ovarian Carcinoma Cells

Objective. We recently reported on the expression and clinical role of molecules that mediate exosome secretion in high-grade serous carcinoma. In the present study, the biological role of these molecules was analyzed. Methods. OVCAR8 and ES-2 ovarian carcinoma cells were studied using a combination of CRISPR/Cas9 technology and two 3D in vitro models—spheroids emulating effusions and alginate scaffolds representing solid lesions. Isolation of exosomes was validated by electron microscopy. TSAP6, NSMASE2, RAB27A, and RAB27B mRNA and protein levels were analyzed using qRT-PCR and Western blotting, respectively. Tumor aggressiveness was studied in vitro using scratch assay, invasion assay, and matrix metalloproteinase (MMP) activity assay and in vivo using a mouse model. Results. In OVCAR8 cells, mRNA expression of TSAP6 and RAB27A was significantly higher in spheroids compared to scaffolds, whereas the opposite was true for NSMASE2 mRNA. In ES-2 cells, TSAP6 and RAB27B mRNA expression was significantly higher in spheroids versus scaffolds. In addition, nSMase2 and TSAP6 protein expression was significantly higher in scaffolds compared to spheroids. CRISPR-edited cells with silencing of NSMASE2, TSAP6, and RAB27A/B had reduced migration, invasion, and MMP activity. Additionally, knockout (KO) of these molecules resulted in significantly diminished exosome secretion. In vivo assay showed that when injected to mice, OVCAR8 RAB27A/B KO cells, as opposed to control OVCAR8 cells, did not form ascites or visible tumor lesions and had reduced MMP expression. Conclusion. The present study provides evidence that different models for culturing ovarian carcinoma cells affect the expression of molecules mediating exosome secretion and that these molecules have a tumor-promoting role. Silencing these molecules may consequently have therapeutic relevance in this cancer.

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