Novel Protocols for Scalable Production of High Quality Purified Small Extracellular Vesicles from Bovine Milk

Neuroblastoma (NBL) is a pediatric cancer that accounts for 15% of childhood cancer mortality. Amplification of the oncogene N-Myc occurs in 20% of NBL patients and is considered high risk as it correlates with aggressiveness, treatment resistance and poor prognosis. Even though the treatment strategies have improved in the recent years, the survival rate of high-risk NBL patients remain poor. Hence, it is crucial to explore new therapeutic avenues to sensitise NBL. Recently, bovine milk-derived extracellular vesicles (MEVs) have been proposed to contain anti-cancer properties. However, the impact of MEVs on NBL cells is not understood. In this study, we characterised MEVs using Western blotting, NTA and TEM. Importantly, treatment of NBL cells with MEVs decreased the proliferation and increased the sensitivity of NBL cells to doxorubicin. Temporal label-free quantitative proteomics of NBL cells highlighted the depletion of proteins involved in cell metabolism, cell growth and Wnt signalling upon treatment with MEVs. Furthermore, proteins implicated in cellular senescence and apoptosis were enriched in NBL cells treated with MEVs. For the first time, this study highlights the temporal proteomic profile that occurs in cancer cells upon MEVs treatment.

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Bovine milk-derived extracellular vesicles enhance inflammation and promote M1 polarization following agricultural dust exposure in mice

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2018.10.017 ◽

2019 ◽

Vol 64 ◽

pp. 110-120 ◽

Cited By ~ 11

Author(s):

Tara M. Nordgren ◽

Art J. Heires ◽

Janos Zempleni ◽

Benjamin J. Swanson ◽

Christopher Wichman ◽

...

Keyword(s):

Extracellular Vesicles ◽

Bovine Milk ◽

Dust Exposure ◽

M1 Polarization

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Postprandial transfer of colostral extracellular vesicles and their protein and miRNA cargo in neonatal calves

10.21203/rs.2.10032/v1 ◽

2019 ◽

Author(s):

Benedikt Kirchner ◽

Dominik Buschmann ◽

Vijay Paul ◽

Michael W. Pfaffl

Keyword(s):

Extracellular Vesicles ◽

Expression Profiles ◽

Bovine Milk ◽

Cell Types ◽

Specific Protein ◽

In Vivo Experiments ◽

Neonatal Calves ◽

Almost All

Abstract Background Extracellular vesicles (EVs) such as exosomes are key regulators of intercellular communication that can be found in almost all bio fluids. Although studies in the last decade have made great headway in discerning the role of EVs in many physiological and pathophysiological processes, the bioavailability and impact of dietary EVs and their cargo still remain to be elucidated. Due to its widespread consumption and high content of EV-associated microRNAs and proteins, a major focus in this field has been set on EVs in bovine milk and colostrum. Despite promising in vitro studies in recent years that show high resiliency of milk EVs to degradation and uptake of milk EV cargo in a variety of intestinal and blood cell types, in vivo experiments continue to be inconclusive and sometimes outright contradictive. Results To resolve this discrepancy, we assessed the potential postprandial transfer of colostral EVs to the circulation of newborn calves by analysing colostrum-specific protein and miRNAs, including specific isoforms (isomiRs) in cells, EV isolations and unfractionated samples from blood and colostrum. Our findings reveal distinct populations of EVs in colostrum and blood from cows that can be clearly separated by density, particle concentration and protein content (BTN1A1, MFGE8). Postprandial blood samples of calves show a time-dependent increase in EVs that share morphological and protein characteristics of colostral EVs. Analysis of miRNA expression profiles by Next-Generation Sequencing gave a different picture however. Although significant postprandial expression changes could only be detected for calf EV samples, expression profiles show very limited overlap with highly expressed miRNAs in colostral EVs or colostrum in general. Conclusions Taken together our results indicate a selective uptake of membrane-associated protein cargo but not luminal miRNAs from colostral EVs into the circulation of neonatal calves.

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Scalable Production of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Under Serum-/Xeno-Free Conditions in a Microcarrier-Based Bioreactor Culture System

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.553444 ◽

2020 ◽

Vol 8 ◽

Cited By ~ 1

Author(s):

Miguel de Almeida Fuzeta ◽

Nuno Bernardes ◽

Filipa D. Oliveira ◽

Ana Catarina Costa ◽

Ana Fernandes-Platzgummer ◽

...

Keyword(s):

Extracellular Vesicles ◽

Mesenchymal Stromal Cell ◽

Culture System ◽

Stromal Cell ◽

Bioreactor Culture ◽

Scalable Production

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Scalable production of high-quality boron nitride nanosheets via a recyclable salt-templating method

Green Chemistry ◽

10.1039/c9gc03285a ◽

2019 ◽

Vol 21 (24) ◽

pp. 6746-6753 ◽

Cited By ~ 2

Author(s):

Yancui Xu ◽

Taotao Li ◽

Weiwei Xu ◽

Chaowei Li ◽

Songfeng E ◽

...

Keyword(s):

Boron Nitride ◽

High Efficiency ◽

High Quality ◽

Templating Method ◽

Boron Nitride Nanosheets ◽

Boron Nitride Nanosheet ◽

Scalable Production

Hollow-structured boron nitride nanosheet cubes were produced via a recyclable salt-templating method, which leads to a high efficiency up to 88.4% on a gram scale.

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Simultaneous Electrochemical Dual‐Electrode Exfoliation of Graphite toward Scalable Production of High‐Quality Graphene

Advanced Functional Materials ◽

10.1002/adfm.201902171 ◽

2019 ◽

Vol 29 (37) ◽

pp. 1902171 ◽

Cited By ~ 14

Author(s):

Yuan Zhang ◽

Youlong Xu

Keyword(s):

High Quality ◽

Scalable Production

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Minute/instant-MOFs: versatile, high quality, ultrafast, scalable production at room temperature

Nanoscale Advances ◽

10.1039/c9na00350a ◽

2019 ◽

Vol 1 (9) ◽

pp. 3379-3382 ◽

Cited By ~ 2

Author(s):

Vijayan Srinivasapriyan

Keyword(s):

Chemical Industry ◽

Room Temperature ◽

Metal Organic Framework ◽

High Quality ◽

Metal Organic ◽

Scalable Synthesis ◽

Scalable Production ◽

Organic Framework

The material demand for metal organic framework (MOF) production necessitates advances in their expedient and scalable synthesis at room temperature, which is pivotal for the chemical industry.

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