In Vitro Macrophage Assay Predicts the In Vivo Anti-inflammatory Potential of Exosomes from Human Mesenchymal Stromal Cells

Pacienza, Natalia; Lee, Ryang Hwa; Bae, Eun-Hye; Kim, Dong-ki; Liu, Qisong; Prockop, Darwin J.; Yannarelli, Gustavo

doi:10.1016/j.omtm.2018.12.003

Cited by 65 publications

(59 citation statements)

References 37 publications

(55 reference statements)

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“…An inflammatory regulating behavior has been also identified for CD14+ EVs that in the respiratory tract may contribute to control both cytokine signaling and IFNγ-induced activation of signal transducer and activator of transcription (STAT), which is responsible for enhancing the expression of proinflammatory genes (STAT-dependent genes) [49].…”

Section: Discussionmentioning

confidence: 99%

Nasal Microbiota Modifies the Effects of Particulate Air Pollution on Plasma Extracellular Vesicles

Mariani

Favero

Carugno

et al. 2020

IJERPH

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Air pollution exposure has been linked to modifications of both extracellular vesicle (EV) concentration and nasal microbiota structure (NMB), which might act as the respiratory health gatekeeper. This study aimed to assess whether an unbalanced NMB could modify the effect of particulate matter (PM) exposure on plasmatic EV levels. Due to two different NMB taxonomical profiles characterized by a widely different relative abundance of the Moraxella genus, the enrolled population was stratified into Mor− (balanced NMB) and Mor+ (unbalanced NMB) groups (Moraxella genus’s cut-off ≤25% and >25%, respectively). EV features were assessed by nanoparticle tracking analysis (NTA) and flow-cytometry (FC). Multivariable analyses were applied on EV outcomes to evaluate a possible association between PM10 and PM2.5 and plasmatic EV levels. The Mor− group revealed positive associations between PM levels and plasmatic CD105+ EVs (GMR = 4.39 p = 0.02) as for total EV count (GMR = 1.92 p = 0.02). Conversely, the Mor+ group showed a negative association between exposure and EV outcomes (CD66+ GMR = 0.004 p = 0.01; EpCAM+ GMR = 0.005 p = 0.01). Our findings provide an insight regarding how a balanced NMB may help to counteract PM exposure effects in terms of plasmatic EV concentration. Further research is necessary to understand the relationship between the host and the NMB to disentangle the mechanism exerted by inhaled pollutants in modulating EVs and NMB.

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Section: Discussionmentioning

confidence: 99%

Nasal Microbiota Modifies the Effects of Particulate Air Pollution on Plasma Extracellular Vesicles

Mariani

Favero

Carugno

et al. 2020

IJERPH

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“…Exosomes are enriched in bioactive molecules, such as proteins, lipids, and nucleic acids, including mRNA, microRNA, and non-coding RNA, which are transferred between cells, thereby influencing the phenotypes and functions of target cells. There is increasing evidence to support exosomes released from different cell types functioning in cell-to-cell communication in physiological processes, such as cardiac remodeling (9, 10), airway remodeling (11, 12), bone remodeling (13–15), and tissue repair (16, 17), as well as pathological processes, including pro-inflammation (18–20)/anti-inflammation (21–23) and cancer (24). However, the involvement of exosomes in cell-to-cell communication in periodontal tissue has not yet been examined.…”

Section: Introductionmentioning

confidence: 99%

Cyclic Stretch Force Induces Periodontal Ligament Cells to Secrete Exosomes That Suppress IL-1β Production Through the Inhibition of the NF-κB Signaling Pathway in Macrophages

et al. 2019

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In the oral mechanical environment, periodontal ligament cells (PDL cells) contribute to maintaining periodontal tissue homeostasis. Recent studies showed that exosomes, which are small vesicles secreted by various types of cells, play a pivotal role in cell-to-cell communication in biological processes. We examined the secretion of exosomes from PDL cells stimulated with cyclic stretch and their role in the inflammatory response of macrophages using the human macrophage cell line THP-1 and human primary monocytes/macrophages. We prepared supernatants from human PDL cells (PDL-sup) stimulated with cyclic stretch. The treatment of macrophages with PDL-sup, but not PDL-sup from unstimulated PDL cells, inhibited the production of IL-1β in LPS/nigericin-stimulated macrophages. The pretreatment of PDL cells with GW4869, an inhibitor of exosome secretion, or siRNA for Rab27B, which controls exosome secretion, abrogated the inhibitory effects of PDL-sup. A transmission electron microscopy analysis demonstrated the existence of exosomes with diameters ranging between 30 and 100 nm in PDL-sup, suggesting that exosomes in PDL-sup contribute to this inhibition. An immunofluorescence microscopy analysis revealed that exosomes labeled with PKH67, a fluorescent dye, were incorporated by macrophages as early as 2 h after the addition of exosomes. Purified exosomes inhibited IL-1β production in LPS/nigericin-stimulated macrophages and the nuclear translocation of NF-κB as well as NF-κB p65 DNA-binding activity in LPS-stimulated macrophages, suggesting that exosomes suppress IL-1β production by inhibiting the NF-κB signaling pathway. Our results indicate that PDL cells in mechanical environments contribute to the maintenance of periodontal immune/inflammatory homeostasis by releasing exosomes.

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“…On the other hand, another criterion is the absence of several proteins, including histones, lamin A/C, glucose-regulated protein 94, Golgi matrix protein 130, and cytochrome C, since strict cellular localization prohibits the enrichment of these intracellular proteins [72]. Although various biological and biochemical assays are used to determine the potency of EVs or exosomes, it is still difficult to establish a single, standard potency assay since the cargos of EVs in vivo are so complex [77,78].…”

Section: Quality Control Of Evsmentioning

confidence: 99%

Mesenchymal stem cell-based cell-free strategies: safe and effective treatments for liver injury

Zhao

Zhang

et al. 2020

Stem Cell Res Ther

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Various hepatoxic factors, such as viruses, drugs, lipid deposition, and autoimmune responses, induce acute or chronic liver injury, and 3.5% of all worldwide deaths result from liver cirrhosis, liver failure, or hepatocellular carcinoma. Liver transplantation is currently limited by few liver donors, expensive surgical costs, and severe immune rejection. Cell therapy, including hepatocyte transplantation and stem cell transplantation, has recently become an attractive option to reduce the overall need for liver transplantation and reduce the wait time for patients. Recent studies showed that mesenchymal stem cell (MSC) administration was a promising therapeutic approach for promoting liver regeneration and repairing liver injury by the migration of cells into liver sites, hepatogenic differentiation, immunoregulation, and paracrine mechanisms. MSCs secrete a large number of molecules into the extracellular space, and soluble proteins, free nucleic acids, lipids, and extracellular vesicles (EVs) effectively repair tissue injury in response to fluctuations in physiological states or pathological conditions. Cell-free-based therapies avoid the potential tumorigenicity, rejection of cells, emboli formation, undesired differentiation, and infection transmission of MSC transplantation. In this review, we focus on the potential mechanisms of MSC-based cell-free strategies for attenuating liver injury in various liver diseases. Secretome-mediated paracrine effects participate in the regulation of the hepatic immune microenvironment and promotion of hepatic epithelial repair. We look forward to completely reversing liver injury through an MSC-based cell-free strategy in regenerative medicine in the near future.

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In Vitro Macrophage Assay Predicts the In Vivo Anti-inflammatory Potential of Exosomes from Human Mesenchymal Stromal Cells

Cited by 65 publications

References 37 publications

Nasal Microbiota Modifies the Effects of Particulate Air Pollution on Plasma Extracellular Vesicles

Nasal Microbiota Modifies the Effects of Particulate Air Pollution on Plasma Extracellular Vesicles

Cyclic Stretch Force Induces Periodontal Ligament Cells to Secrete Exosomes That Suppress IL-1β Production Through the Inhibition of the NF-κB Signaling Pathway in Macrophages

Mesenchymal stem cell-based cell-free strategies: safe and effective treatments for liver injury

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