Advanced in vitro exposure systems.

9. Dec. 2021

Iota-carrageenan extracted from red algae is a potent inhibitor of SARS-CoV-2 infection in reconstituted human airway epithelia

https://doi.org/10.1016/j.bbrep.2021.101187

David Bovard b, Marco van der Toorn b, Walter K. Schlage a, Samuel Constant c, Kasper Renggli b, Manuel C. Peitsch b, Julia Hoeng b,
a Biology Consultant, Max-Baermann-Str. 21, 51429, Bergisch Gladbach, Germany
b PMI R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland
c Epithelix Sarl, 18 Chemin des Aulx, Plan-les-Ouates, 1228, Geneva, Switzerland

 

This study successfully demonstrates the exposure of human bronchial epithelial cultures to defined doses of nebulized Iota-carrageenan which were reproducibly generated and administered using the VITROCELL Cloud 12 system. 
The aim of this study was to further investigate the efficacy and safety of IC treatment on SARS-CoV-2 infection by using advanced in vitro models of human respiratory epithelium, the primary target and entry port of SARS-CoV-2. The experimental models were 3D cultures of reconstituted bronchial and nasal epithelia, representing the surface of the human upper respiratory tract. This apical exposure of reconstructed epithelia more closely mimics real-life exposure conditions and the absence of toxicity or any functional or structural impairment of the bronchial mucociliary epithelium demonstrates that topical treatment with nebulized IC is well tolerated at the effective concentrations. 

 

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3. Nov. 2022

Characterization of smoke and aerosol deliveries from combustible cigarettes, heated tobacco products and electronic nicotine delivery systems in the Vitrocell® Mammalian 6/48 exposure module

https://doi.org/10.1016/j.toxrep.2022.11.001

Brian M. Keyser1, Robert Leverette1, Michael Hollings2, Adam Seymour2, Randy A. Weidman3, Carlton J. Bequette3, Kristen Jordan1
1 RAI Services Company; Scientific & Regulatory Affairs, 401 North Main Street, Winston-Salem, NC 27101, USA
2 Labcorp Early Development Laboratories Ltd., Harrogate, North Yorkshire, UK
3 RJ Reynolds Tobacco Company; 950 Reynolds Blvd., Winston-Salem, NC 27106, USA

 

Highlights

  • Characterization of two 48 well exposure modules with three different product types
  • Comparison of these exposure modules using four different dosimetry techniques
  • Ability to differentiate the aerosol deliveries between different dilution airflows

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22. Aug. 2022

Carbon nanoparticles adversely affect CFTR expression and toxicologically relevant pathways

https://doi.org/10.1038/s41598-022-18098-8

Torben Stermann1, Thach Nguyen1, Burkhard Stahlmecke2, Ana Maria Todea2, Selina Woeste1, Inken Hacheney1, Jean Krutmann1,3, Klaus Unfried1, Roel P. F. Schins1 & Andrea Rossi1
1IUF – Leibniz-Research Institute for Environmental Medicine, Auf’m Hennekamp 50, 40225 Duesseldorf, Germany. 
2IUTA – Institut für Energie- und Umwelttechnik e.V., Duisburg, Germany. 
3Medical Faculty, Heinrich Heine University, Düsseldorf, Germany. *email: andrea.rossi@iuf-duesseldorf.de

 

In the present study the 16HBE14o- cells were exposed in an automated exposure station at air-liquid interface conditions, using the controlled generation of carbon nanoparticles (CNP) aerosols by spark-ablation. This study reports that CNP exposure leads to decrease cystic fibrosis transmembrane conductance regulator (CFTR) expression accompanied by transcriptomic signs of oxidative stress, apoptosis and DNA damage.

 

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21. Jun. 2022

Exposure to naphthalene and β-pinene-derived secondary organic aerosol induced divergent changes in transcript levels of BEAS-2B cells

https://doi.org/10.1016/j.envint.2022.107366

Michal Pardoa, Svenja Offerbc, Elena Hartnerbc, Sebastiano Di Bucchianicob, Christoph Bisigb, Stefanie Bauerb, Jana Pantzkebc, Elias J. Zimmermannbc, XinCaobc, Stephanie Binderbc, Evelyn Kuhnb, Anja Huberb, Seongho Jeongbc, Uwe Käferbc, Eric Schneiderc,[...]

a Department of Earth and Planetary Sciences, Faculty of Chemistry, Weizmann Institute of Science, 234 Herzl Street, POB 26, ISR-7610001 Rehovot, Israel
b Joint Mass Spectrometry Center (JMSC) at Comprehensive Molecular Analytics (CMA), Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
c Joint Mass Spectrometry Center (JMSC) at Analytical Chemistry, Institute of Chemistry, University of Rostock, Dr.-Lorenz-Weg 2, D-18059 Rostock, Germany
d Department of Environmental and Biological Sciences, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, FI-70210 Kuopio, Finland
e University of the Bundeswehr Munich, Institute for Chemistry and Environmental Engineering, Werner- Heisenberg-Weg 39, D-85577 Neubiberg, Germany
f Institute for Environmental Studies, Faculty of Science, Charles University, Albertov 6, CZE-12800 Prague, Czech Republic
g Department of Applied Physics, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, FI-70210 Kuopio, Finland
h Institute of Energy and Climate Research, Troposphere (IEK-8), Forschungszentrum Jülich GmbH, Wilhelm-Johen-Str., D-52428 Jülich, Germany
i Department of Environmental Sciences, University of Basel, Klingelbergstr. 27, CH-4056 Basel, Switzerland
j Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Str. 10, D-13125 Berlin, Germany
k Institute of Computational Biology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
l The Mantoux Bioinformatics Institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 76100, Israel

 

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15. Jun. 2022

Characterization of Aerosol Deliveries from Combustible Cigarettes, Heated Tobacco Products, and Electronic Nicotine Delivery Systems Using the Vitrocell Ames 48

DOI: 10.1089/aivt.2022.0001

Brian M. Keyser,1 Robert Leverette,1 Michael Hollings,2 Adam Seymour,2 Randy J. Weidman,3 Carlton J. Bequette,3 and Kristen Jordan1
1 Scientific & Regulatory Affairs, RAI Services Company, Winston-Salem, North Carolina, USA.
2 Labcorp Early Development Laboratories Ltd., Harrogate, North Yorkshire, United Kingdom.
3 RJ Reynolds Tobacco Company, Winston-Salem, North Carolina, USA

 

This study utilized a Vitrocell Ames 48 exposure module climatic chamber. Cigarette smoke and eHTP/ENDS aerosol was generated using a Vitrocell VC10. Different concentrations of whole smoke or aerosol were achieved by altering the diluting airflow using mass flow controllers  The dosimetry measure used for assessing both combustible and NGTP aerosols in this characterization exercise was the laser photometer purchased from Vitrocell Systems and harmonized for each tobacco product type used in this study. To evaluate the multiple dosimetry techniques, pairwise comparisons were made between the two Vitrocell Ames 48 exposure modules for each of the three test articles. 

 

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Categories: Publications

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15. Apr. 2022

Aerosol–Cell Exposure System Applied to Semi-Adherent Cells for Aerosolization of Lung Surfactant and Nanoparticles Followed by High Quality RNA Extraction

https://doi.org/10.3390/nano12081362

Mélanie M. Leroux 1 , Romain Hocquel 1, Kevin Bourge 1 , Boštjan Kokot 2 , Hana Kokot 2 , Tilen Koklič 2, Janez Štrancar 2, Yaobo Ding 3 , Pramod Kumar 3, Otmar Schmid 3 , Bertrand H. Rihn 1, Luc Ferrari 1 and Olivier Joubert 1
1 Institut Jean Lamour, UMR CNRS 7198, Université de Lorraine, CNRS, IJL, F-54000 Nancy, France;
2 Jožef Stefan Institute, Department of Condensed Matter Physics, 1000 Ljubljana, Slovenia;
3 Institute of Lung Health and Immunity, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany;

This study reports the optimization of an innovative air–liquid interface system using a cloud settling exposure system by VITROCELL® Systems for pre-coating of the cells with surfactant lung lining fluid and subsequent NP exposure, combined with an accurate micrometric balance to measure cell exposure in real-time.


 

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15. Apr. 2022

Aerosol–Cell Exposure System Applied to Semi-Adherent Cells for Aerosolization of Lung Surfactant and Nanoparticles Followed by High Quality RNA Extraction

https://doi.org/10.3390/nano12081362


Mélanie M. Leroux 1 , Romain Hocquel 1, Kevin Bourge 1 , Boštjan Kokot 2 , Hana Kokot 2 , Tilen Kokliˇc 2, Janez Štrancar 2, Yaobo Ding 3 , Pramod Kumar 3, Otmar Schmid 3 , Bertrand H. Rihn 1, Luc Ferrari 1 and Olivier Joubert 1
1 Institut Jean Lamour, UMR CNRS 7198, Université de Lorraine, CNRS, IJL, F-54000 Nancy, France
2 Jožef Stefan Institute, Department of Condensed Matter Physics, 1000 Ljubljana, Slovenia
3 Institute of Lung Health and Immunity, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany

The goal of this work was to refine an ALI pre-established protocol for the VITROCELL® Cloud 6 system. Therefore, after addressing each crucial step, (i.e., the use of very low concentrations of NP, the deposition of a homogeneous layer of surfactant, the specific use of semi-adherent cells, and finally the enhancement of the extraction yield of RNA to carry out transcriptomic studies), we present here for the first time a robust almost ready-to-use protocol. This one will be helpful for nanotoxicologists interested in developing such methodologies.

 

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27. Mar. 2022

Nrf2 Responses of Commercial Cigarette Whole Smoke and Aerosol from Six Electronic Nicotine Delivery Systems (ENDS) in a 3D Human Airway Model

Poster SOT 2022, 61st Annual Meeting and ToxExpo, March 27-31, San Diego, USA

Brian M. Keyser1, John Wertman1, Michael Hollings2, Robert Bedford2, and Kristen Jordan1
1 Scientific & Regulatory Affairs, RAI Services Company, Winston-Salem, NC; 
2 Labcorp Early Development Laboratories Ltd., Harrogate, UK

In this study whole smoke from a marketed combustible cigarette and whole aerosol from four different ENDS were evaluated on cell viability and Nrf2 response in a 3D human airway model transfected with a luciferase Nrf2 promoter.
Whole aerosol was generated using a Vitrocell ® VC10® Smoke Exposure System. The tissues were exposed to whole smoke from a market combustible generated under Health Canada Intense regime.These data show that the 3D Nrf2 EpiAirway™ in vitro model can be used to assess and discriminate responses from a biomarker (oxidative stress) for disease pathways associated with tobacco product usage.

 

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27. Mar. 2022

Cytotoxicity Assessment of Electronic Nicotine Delivery Systems (ENDS) and Combustible Cigarette Aerosols Utilizing Standard and Whole Aerosol Exposure Approaches in the Neutral Red Uptake Assay

Poster SOT 2022, 61st Annual Meeting and ToxExpo, March 27-31, San Diego, USA

Robert Leverette1, Thomas Shutsky1, John Wertman1, Katarina Aleksa2, Dhatri Lakshmanan2, Rebecca Payne3, Kristen Jordan1
1Scientific & Regulatory Affairs, RAI Services Company, Winston-Salem, NC, USA; 
2Labstat International Inc. Kitchener, ON, Canada;
3Labcorp Early Development Laboratories Ltd., Harrogate, UK

This poster shows whole aerosol exposures of combustible and next generation tobacco products, including Electronic Nicotine Delivery Systems. A Vitrocell® VC10® robot generated and delivered aerosols to the Mammalian 6/48 aerosol dilution and exposure system, with up to 7 concurrent doses plus a clean air control. Dosimetry module allowed the capture and quantification of deposited aerosol constituents (nicotine, glycerol and carbonyls). The study utilized the Neutral Red Uptake (NRU) assay in which mammalian cells were exposed to either combined TPM + GVP (submerged culture) or Whole Aerosol (ALI).

 

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27. Mar. 2022

In Vitro Cytotoxicity Assessment of 3D Human Airway Tissue Following Exposure to Whole Aerosol/Smoke Generated from Electronic and Combustible Cigarettes

Poster SOT 2022, 61st Annual Meeting and ToxExpo, March 27-31, San Diego, USA

Thomas Shutsky1, Brian M. Keyser1, Kristen Jordan1, Michael Hollings2, and Emma Rothwell2
1Scientific & Regulatory Affairs, RAI Services Company, Winston-Salem, NC; 
2Labcorp Early Development Laboratories Ltd., Harrogate, UK

In this study, EpiAirway™ tissues were exposed to whole aerosol/smoke generated from six different Vuse Alto electronic nicotine delivery system test articles with various nicotine concentrations and a combustible cigarette. A Vitrocell® VC10® robot was used to generate whole aerosol/smoke with either a modified ISO or Health Canada Intense smoking regimen. Whole smoke/aerosol was puffed with clean air with a series of different air flows to achieve the delivered dose range. 

 

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