scholarly journals Monocyte‐derived extracellular vesicles stimulate cytokine secretion and gene expression of matrix metalloproteinases by mesenchymal stem/stromal cells

FEBS Journal ◽  
2018 ◽  
Vol 285 (12) ◽  
pp. 2337-2359 ◽  
Author(s):  
Arjen Gebraad ◽  
Roman Kornilov ◽  
Sippy Kaur ◽  
Susanna Miettinen ◽  
Suvi Haimi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Matrix Metalloproteinases ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Cytokine Secretion

scholarly journals Long-Term Impact of Zinc Oxide Nanoparticles on Differentiation and Cytokine Secretion of Human Adipose-Derived Stromal Cells

Materials ◽  
2019 ◽  
Vol 12 (11) ◽  
pp. 1823 ◽  
Author(s):  
Katrin Radeloff ◽  
Andreas Radeloff ◽  
Mario Ramos Tirado ◽  
Agmal Scherzad ◽  
Rudolf Hagen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zinc Oxide ◽  
Stromal Cells ◽  
Zinc Oxide Nanoparticles ◽  
Caspase 3 ◽  
Cytokine Secretion ◽  
Oxide Nanoparticles ◽  
Zno Nps ◽  
The Impact

Zinc oxide nanoparticles (ZnO-NPs) are widely utilized, for example in manufacturing paints and in the cosmetic industry. In addition, there is raising interest in the application of NPs in stem cell research. However, cytotoxic, genotoxic and pro-inflammatory effects were shown for NPs. The aim of this study was to evaluate the impact of ZnO-NPs on cytokine secretion and differentiation properties of human adipose tissue-derived stromal cells (ASCs). Human ASCs were exposed to the subtoxic concentration of 0.2 µg/mL ZnO-NPs for 24 h. After four weeks of cultivation, adipogenic and osteogenic differentiation procedures were performed. The multi-differentiation potential was confirmed histologically and using polymerase chain reaction (PCR). In addition, the gene expression of IL-6, IL-8, vascular endothelial growth factor (VEGF) and caspase 3 was analyzed. Over the course of four weeks after ZnO-NPs exposure, no significant differences were detected in the gene expression of IL-6, IL-8, VEGF and caspase 3 compared to non-exposed cells. The differentiation was also not affected by the ZnO-NPs. These findings underline the fact, that functionality of ASCs is likely to be unaffected by ZnO-NPs, despite a long-term disposition of NPs in the cells, supposing that the starting concentration was safely in the non-toxic range. This might provide important information for single-use nanomedical applications of ZnO-NPs.

Gene expression of matrix metalloproteinases are observed in the stromal cells and mediated by cytokines in gastrointestinal tract cancers

1995 ◽  
Vol 108 (4) ◽  
pp. A522
Author(s):  
Y. Otani ◽  
Y. Sakurai ◽  
K. Kameyama ◽  
K. Kumai ◽  
I. Okazaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastrointestinal Tract ◽  
Matrix Metalloproteinases ◽  
Stromal Cells

scholarly journals Characterization and miRNA Profiling of Extracellular Vesicles from Human Osteoarthritic Subchondral Bone Multipotential Stromal Cells (MSCs)

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Clara Sanjurjo-Rodríguez ◽  
Rachel E. Crossland ◽  
Monica Reis ◽  
Hemant Pandit ◽  
Xiao-nong Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Vesicles ◽  
Subchondral Bone ◽  
Cross Talk ◽  
Stromal Cells ◽  
Cell Communication ◽  
Cartilage Regeneration ◽  
Chondrocyte Viability ◽  
Mirna Profiling ◽  
The Cross

Osteoarthritis (OA) is a heterogeneous disease in which the cross-talk between the cells from different tissues within the joint is affected as the disease progresses. Extracellular vesicles (EVs) are known to have a crucial role in cell-cell communication by means of cargo transfer. Subchondral bone (SB) resident cells and its microenvironment are increasingly recognised to have a major role in OA pathogenesis. The aim of this study was to investigate the EV production from OA SB mesenchymal stromal cells (MSCs) and their possible influence on OA chondrocytes. Small EVs were isolated from OA-MSCs, characterized and cocultured with chondrocytes for viability and gene expression analysis, and compared to small EVs from MSCs of healthy donors (H-EVs). OA-EVs enhanced viability of chondrocytes and the expression of chondrogenesis-related genes, although the effect was marginally lower compared to that of the H-EVs. miRNA profiling followed by unsupervised hierarchical clustering analysis revealed distinct microRNA sets in OA-EVs as compared to their parental MSCs or H-EVs. Pathway analysis of OA-EV miRNAs showed the enrichment of miRNAs implicated in chondrogenesis, stem cells, or other pathways related to cartilage and OA. In conclusion, OA SB MSCs were capable of producing EVs that could support chondrocyte viability and chondrogenic gene expression and contained microRNAs implicated in chondrogenesis support. These EVs could therefore mediate the cross-talk between the SB and cartilage in OA potentially modulating chondrocyte viability and endogenous cartilage regeneration.

scholarly journals Targeting Extracellular Vesicle Secretion As a Strategy to Overcome Microenvironment Mediated Drug Resistance in Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3733-3733
Author(s):  
Palani Kumar Kumar ◽  
Saravanan Ganesan ◽  
Nithya Balasundaram ◽  
Sachin David ◽  
Arvind Venkatraman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Resistance ◽  
Cell Lines ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Myeloid Leukemia ◽  
Extracellular Vesicle ◽  
Akt Signaling ◽  
Leukemic Cells ◽  
Stromal Microenvironment

Increasing evidence suggests that bone marrow microenvironment act as a sanctuary site for acute myeloid leukemia (AML) cells and provides protection from conventional chemotherapy agents. Recently, extracellular vesicles (EVs) have attracted substantial attention as a carrier of complex intercellular information by transferring microRNA, mRNA and proteins. We undertook a study to delineate the molecular mediators and potential role of extracellular vesicles in stromal microenvironment mediated drug resistance in AML. We performed a series of in vitro experiments with AML cell lines (U937, THP-1, Kasumi-1) and primary cells to evaluate their response to daunorubicin (DNR) and cytarabine (AraC) with stromal cells (HS-5 cell line). Towards this we co-cultured the leukemic cells with stromal cells in a contact dependent and contact independent (transwell plates) system and with EVs derived from HS-5 culture media using well established methods (Suzanne et al, Blood 2015). The percentage of viability was calculated using Annexin V/7AAD staining by flow cytometry. Gene expression profiling was done using Agilent Human Whole Genome 8x60K Gene Expression Array. The quantification of extracellular vesicle was performed using NanoSight LM10. Direct stromal co-culture experiments with AML cells demonstrated a significant stromal cell mediated protective effect against AraC and DNR in cell lines (figure 1A) and primary cells [AraC p < 0.01; DNR p < 0.001 (n=50)]. A similar significant protective effect was also seen in contact independent system and EVs alone treated leukemic cells (supplemented in place of HS-5 co-culture). Gene expression profiling analysis of leukemic cells (U937) and stromal cell (HS-5) post co-culture revealed a bidirectional enrichment of genes involved in extracellular vesicle biogenesis and secretion (p < 0.001) along with a significant dysregulation of PI3K-AKT signaling in leukemic cells. We have previously reported that stromal EVs activates PI3K-AKT signaling and mediates drug resistance in leukemic cells similar to direct stromal co-culture (Blood 2017 130:1160). In addition to PI3K-AKT signaling, our qPCR validation also confirmed the significant up regulation of genes which are involved in EVs secretion (RAB27A, RAB35 and VAMP7) in leukemic cells as well as stromal cells post co-culture (figure 1B). Hence, we quantified the amount of EVs production in leukemic and stromal cells post 48hrs of co-culture where the number of EVs showed a trend towards increase in co-cultured leukemic and stromal cells when compared to the cells cultured alone (figure 1C). We also noted that treatment with neutral sphingomyelinease inhibitor GW4869 a known inhibitor of EVs secretion was able overcome the stroma mediated drug resistance significantly in leukemic cell lines (figure 1D) and also in primary AML cells [AraC p < 0.01; DNR p < 0.001 (n=6)]. Our results illustrate that reciprocal interaction of leukemic and stromal cells influences the secretion of extracellular vesicles and plays a significant role in mediating drug resistance. We further demonstrated that inhibiting extracellular vesicles secretion was able to overcome the stromal microenvironment mediated drug resistance in AML illustrating a potentially novel therapeutic strategy. Additional studies are required to explore and characterize the cargo (microRNA and proteins) in detail of these EVs and the mechanism/s by which they mediate drug resistance. Disclosures No relevant conflicts of interest to declare.

scholarly journals Small Extracellular Vesicles from adipose derived stromal cells significantly attenuate in vitro the NF-κB dependent inflammatory/catabolic environment of osteoarthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carola Cavallo ◽  
Giulia Merli ◽  
Rosa Maria Borzì ◽  
Nicoletta Zini ◽  
Stefania D’Adamo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Nuclear Translocation ◽  
Protein Release ◽  
Biologically Active ◽  
Size Exclusion ◽  
Chromatography Method ◽  
Adipose Derived Stromal Cells

AbstractThe therapeutic ability of Mesenchymal Stem/Stromal Cells to address osteoarthritis (OA) is mainly related to the secretion of biologically active factors, which can be found within their secreted Extracellular Vesicles including small Extracellular Vesicles (sEV). Aim of this study was to investigate the effects of sEV from adipose derived stromal cells (ADSC) on both chondrocytes and synoviocytes, in order to gain insights into the mechanisms modulating the inflammatory/catabolic OA environment. sEV, obtained by a combined precipitation and size exclusion chromatography method, were quantified and characterized, and administered to chondrocytes and synoviocytes stimulated with IL-1β. Cellular uptake of sEV was evaluated from 1 to 12 h. Gene expression and protein release of cytokines/chemokines, catabolic and inflammatory molecules were analyzed at 4 and 15 h, when p65 nuclear translocation was investigated to study NF-κB pathway. This study underlined the potential of ADSC derived sEV to affect gene expression and protein release of both chondrocytes and synoviocytes, counteracting IL-1β induced inflammatory effects, and provided insights into their mechanisms of action. sEV uptake was faster in synoviocytes, where it also elicited stronger effects, especially in terms of cytokine and chemokine modulation. The inflammatory/catabolic environment mediated by NF-κB pathway was significantly attenuated by sEV, which hold promise as new therapeutic strategy to address OA.

Effects of Extracellular Vesicles Derived from Mesenchymal Stem/Stromal Cells on Liver Diseases

2019 ◽  
Vol 14 (5) ◽  
pp. 442-452 ◽  
Author(s):  
Wenjie Zheng ◽  
Yumin Yang ◽  
Russel Clive Sequeira ◽  
Colin E. Bishop ◽  
Anthony Atala ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Liver Diseases ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Chronic Liver Injury ◽  
Mediated Effects ◽  
Therapeutic Benefits

Therapeutic effects of Mesenchymal Stem/Stromal Cells (MSCs) transplantation have been observed in various disease models. However, it is thought that MSCs-mediated effects largely depend on the paracrine manner of secreting cytokines, growth factors, and Extracellular Vesicles (EVs). Similarly, MSCs-derived EVs also showed therapeutic benefits in various liver diseases through alleviating fibrosis, improving regeneration of hepatocytes, and regulating immune activity. This review provides an overview of the MSCs, their EVs, and their therapeutic potential in treating various liver diseases including liver fibrosis, acute and chronic liver injury, and Hepatocellular Carcinoma (HCC). More specifically, the mechanisms by which MSC-EVs induce therapeutic benefits in liver diseases will be covered. In addition, comparisons between MSCs and their EVs were also evaluated as regenerative medicine against liver diseases. While the mechanisms of action and clinical efficacy must continue to be evaluated and verified, MSCs-derived EVs currently show tremendous potential and promise as a regenerative medicine treatment for liver disease in the future.

scholarly journals Interleukin-1β Induced Matrix Metalloproteinase Expression in Human Periodontal Ligament-Derived Mesenchymal Stromal Cells under In Vitro Simulated Static Orthodontic Forces

2021 ◽  
Vol 22 (3) ◽  
pp. 1027
Author(s):  
Christian Behm ◽  
Michael Nemec ◽  
Alice Blufstein ◽  
Maria Schubert ◽  
Xiaohui Rausch-Fan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Periodontal Ligament ◽  
Induced Expression ◽  
Gene And Protein Expression ◽  
Tensile Strains ◽  
Orthodontic Forces ◽  
Low Magnitude

The periodontal ligament (PDL) responds to applied orthodontic forces by extracellular matrix (ECM) remodeling, in which human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) are largely involved by producing matrix metalloproteinases (MMPs) and their local inhibitors (TIMPs). Apart from orthodontic forces, the synthesis of MMPs and TIMPs is influenced by the aseptic inflammation occurring during orthodontic treatment. Interleukin (IL)-1β is one of the most abundant inflammatory mediators in this process and crucially affects the expression of MMPs and TIMPs in the presence of cyclic low-magnitude orthodontic tensile forces. In this study we aimed to investigate, for the first time, how IL-1β induced expression of MMPs, TIMPs and how IL-1β in hPDL-MSCs was changed after applying in vitro low-magnitude orthodontic tensile strains in a static application mode. Hence, primary hPDL-MSCs were stimulated with IL-1β in combination with static tensile strains (STS) with 6% elongation. After 6- and 24 h, MMP-1, MMP-2, TIMP-1 and IL-1β expression levels were measured. STS alone had no influence on the basal expression of investigated target genes, whereas IL-1β caused increased expression of these genes. In combination, they increased the gene and protein expression of MMP-1 and the gene expression of MMP-2 after 24 h. After 6 h, STS reduced IL-1β-induced MMP-1 synthesis and MMP-2 gene expression. IL-1β-induced TIMP-1 gene expression was decreased by STS after 6- and 24-h. At both time points, the IL-1β-induced gene expression of IL-1β was increased. Additionally, this study showed that fetal bovine serum (FBS) caused an overall suppression of IL-1β-induced expression of MMP-1, MMP-2 and TIMP-1. Further, it caused lower or opposite effects of STS on IL-1β-induced expression. These observations suggest that low-magnitude orthodontic tensile strains may favor a more inflammatory and destructive response of hPDL-MSCs when using a static application form and that this response is highly influenced by the presence of FBS in vitro.

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