Hot EVs – How temperature affects extracellular vesicles

Schulz, Eilien; Karagianni, Anna; Koch, Marcus; Fuhrmann, Gregor

doi:10.1016/j.ejpb.2019.11.010

Cited by 51 publications

(48 citation statements)

References 30 publications

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“…We found that the dose-dependent antibacterial activity of Cbv34 OMVs was conserved during 28 days of storage. This result matches recent findings that show extracellular vesicles' inherent stability under different storage conditions [49,50].…”

Section: Discussionsupporting

confidence: 92%

Myxobacteria-Derived Outer Membrane Vesicles: Potential Applicability Against Intracellular Infections

Goes

Lapuhs

Kuhn

et al. 2020

Cells

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In 2019, it was estimated that 2.5 million people die from lower tract respiratory infections annually. One of the main causes of these infections is Staphylococcus aureus, a bacterium that can invade and survive within mammalian cells. S. aureus intracellular infections are difficult to treat because several classes of antibiotics are unable to permeate through the cell wall and reach the pathogen. This condition increases the need for new therapeutic avenues, able to deliver antibiotics efficiently. In this work, we obtained outer membrane vesicles (OMVs) derived from the myxobacteria Cystobacter velatus strain Cbv34 and Cystobacter ferrugineus strain Cbfe23, that are naturally antimicrobial, to target intracellular infections, and investigated how they can affect the viability of epithelial and macrophage cell lines. We evaluated by cytometric bead array whether they induce the expression of proinflammatory cytokines in blood immune cells. Using confocal laser scanning microscopy and flow cytometry, we also investigated their interaction and uptake into mammalian cells. Finally, we studied the effect of OMVs on planktonic and intracellular S. aureus. We found that while Cbv34 OMVs were not cytotoxic to cells at any concentration tested, Cbfe23 OMVs affected the viability of macrophages, leading to a 50% decrease at a concentration of 125,000 OMVs/cell. We observed only little to moderate stimulation of release of TNF-alpha, IL-8, IL-6 and IL-1beta by both OMVs. Cbfe23 OMVs have better interaction with the cells than Cbv34 OMVs, being taken up faster by them, but both seem to remain mostly on the cell surface after 24 h of incubation. This, however, did not impair their bacteriostatic activity against intracellular S. aureus. In this study, we provide an important basis for implementing OMVs in the treatment of intracellular infections.

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Section: Discussionsupporting

confidence: 92%

Myxobacteria-Derived Outer Membrane Vesicles: Potential Applicability Against Intracellular Infections

Goes

Lapuhs

Kuhn

et al. 2020

Cells

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“…CD73, whose beneficial action in graft‐versus‐host‐disease [ 12 ] and cartilage repair [ 13 ] was previously emphasized, was found to play a fundamental role in the exosome‐mediated acceleration of the scratch wound closure of keratinocytes. The loss of activity that was observed upon heating the HS‐5 exosomes at 65 °C also suggests that thermal treatment at higher temperatures, which was previously shown to not substantially affect the morphology or uptake behavior of the vesicles, [ 54 ] should be carefully examined as it may be detrimental to the exosome functionality. Notably, the HaCaT cell model used in this work is frequently used to study skin biology for it retains a normal differentiation capacity, though differing in several aspects from primary human keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

Exosomes for Wound Healing: Purification Optimization and Identification of Bioactive Components

et al. 2020

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Human mesenchymal stem cell exosomes have been shown to promote cutaneous wound healing. Their bioactivity is most often attributed to their protein and nucleic acid components, while the function of exosomal lipids remains comparatively unexplored. This work specifically assesses the involvement of lipids and the transmembrane enzyme CD73 in the exosomes' biological activity in stimulating the cutaneous wound healing process. Since exosome preparation processes are not harmonized yet, certain production and purification parameters are first systematically investigated, enabling the optimization of a standardized protocol delivering high exosome integrity, yield, and purity. An in situ enzymatic assay is introduced to specifically assess the vesicle functionality, and quantitative proteomics is employed to establish the cell culture conditions yielding a stable exosome protein profile. Using a combination of in vitro approaches, CD73 and constitutional lipids of HPV-16 E6/E7 transformed human bone marrow stromal cell-derived exosomes are identified as key bioactive components promoting the exosome-driven acceleration of processes required for wound repair. A pilot wound healing study in mice indeed suggests a role of lipids in the exosomes' biological activity. Strikingly, the extent of the bioactivity of these exosomal components is found to be dependent on the target cell type.

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“…Hence, the sterility of the drug product is critical. EVs were recently shown to maintain stability under autoclave temperatures [88]. More importantly, EV-based drug products were reported to be eligible for sterile filtration using filters with 200 nm pore sizes [87].…”

Section: Production Feasibility and Compliance Of Extracellular Vesicmentioning

confidence: 99%

Repurposing Antiviral Protease Inhibitors Using Extracellular Vesicles for Potential Therapy of COVID-19

Kumar

Zhi

Mukherji

et al. 2020

Viruses

111

104

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In January 2020, Chinese health agencies reported an outbreak of a novel coronavirus-2 (CoV-2) which can lead to severe acute respiratory syndrome (SARS). The virus, which belongs to the coronavirus family (SARS-CoV-2), was named coronavirus disease 2019 (COVID-19) and declared a pandemic by the World Health Organization (WHO). Full-length genome sequences of SARS-CoV-2 showed 79.6% sequence identity to SARS-CoV, with 96% identity to a bat coronavirus at the whole-genome level. COVID-19 has caused over 133,000 deaths and there are over 2 million total confirmed cases as of 15 April 2020. Current treatment plans are still under investigation due to a lack of understanding of COVID-19. One potential mechanism to slow disease progression is the use of antiviral drugs to either block the entry of the virus or interfere with viral replication and maturation. Currently, antiviral drugs, including chloroquine/hydroxychloroquine, remdesivir, and lopinavir/ritonavir, have shown effective inhibition of SARS-CoV-2 in vitro. Due to the high dose needed and narrow therapeutic window, many patients are experiencing severe side effects with the above drugs. Hence, repurposing these drugs with a proper formulation is needed to improve the safety and efficacy for COVID-19 treatment. Extracellular vesicles (EVs) are a family of natural carriers in the human body. They play a critical role in cell-to-cell communications. EVs can be used as unique drug carriers to deliver protease inhibitors to treat COVID-19. EVs may provide targeted delivery of protease inhibitors, with fewer systemic side effects. More importantly, EVs are eligible for major aseptic processing and can be upscaled for mass production. Currently, the FDA is facilitating applications to treat COVID-19, which provides a very good chance to use EVs to contribute in this combat.

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Hot EVs – How temperature affects extracellular vesicles

Cited by 51 publications

References 30 publications

Myxobacteria-Derived Outer Membrane Vesicles: Potential Applicability Against Intracellular Infections

Myxobacteria-Derived Outer Membrane Vesicles: Potential Applicability Against Intracellular Infections

Exosomes for Wound Healing: Purification Optimization and Identification of Bioactive Components

Repurposing Antiviral Protease Inhibitors Using Extracellular Vesicles for Potential Therapy of COVID-19

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