Advanced in vitro exposure systems.

27. Mar. 2020

Reliable in vitro Exposure Systems for Screening of Antiviral Lead Compounds against Coronavirus (COVID-19 / SARS-CoV-2)

VITROCELL Application Note for Highly efficient and realistic application of aerosolized drugs to ­human cells of the respiratory tract under physiologic conditions

In inhalation therapy, drugs are deposited as aerosols on cells of the respiratory tract from the nasal or lung region. Physiologically realistic in vitro cell culture models of the pulmonary epithelium and the air-blood barrier as well as from the nasal region are commercially available. Recently, these models have been refined to mimic  SARS-CoV-2 infections.

VITROCELL Application Note.

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26. Mar. 2020

Screening antiviraler pharmazeutischer Leitwirkstoffe gegen das Coronavirus (COVID-19 / SARS-CoV-2)

VITROCELL in vitro Expositionssysteme für hocheffiziente und realistische Applikation aerosolisierter Medikamente auf menschliche Zellen des Atemtraktes unter physiologischen Bedingungen.

In der Inhalationstherapie werden pharmazeutische Präparate als Aerosole auf Zellen des Atemtraktes im Nasen- oder Lungenbereich appliziert. Zur präklinischen Entwicklung neuer Arzneimittel werden dafür oft kommerziell erhältliche, physiologisch relevante in vitro Zellkulturmodelle des Nasen-, Rachen- oder Lungenepithels verwendet. In jüngster Zeit wurden diese Modelle verfeinert, um SARS-CoV-2 Infektionen nachzuahmen.

VITROCELL Anwendungshinweis.

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24. Mar. 2020

Comparison of Vapor and Liquid Phase Acrolein Exposures to Air Liquid Interface (ALI) Cell Cultures

David H. Brandwein, F. Adam Bettmann, Michael P. DeLorme, Alan T. Eveland, Lawrence M. Milchak 
3M Corporate Toxicology and Environmental Science, St. Paul, MN
 

The STL is working to develop an in vitro screening ALI model to assess the acute respiratory irritation potential for new chemicals. These experiments examined multiple aspects of the model, including different cell culture systems (A549 and EpiAirway), different exposure methods (dynamic vapor and liquid phase), and different post exposure periods, all using acrolein as a model respiratory irritant. The goal was to better understand the critical parameters of the cell systems and exposure methods to enable the development of a consistent screening model, while gaining clarity of the dosimetry. 

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7. Sep. 2019

Application of a multi‑layer systems toxicology framework for in vitro assessment of the biological effects of Classic Tobacco e‑liquid and its corresponding aerosol using an e‑cigarette device

https://doi.org/10.1007/s00204-019-02565-9


Anita R. Iskandar, Filippo Zanetti, Diego Marescotti, Bjorn Titz, Alain Sewer, Athanasios Kondylis, Patrice Leroy, Vincenzo Belcastro, Laura Ortega Torres, Stefano Acali, Shoaib Majeed, Sandro Steiner, Keyur Trivedi, Emmanuel Guedj, Celine Merg, Thomas Schneider, Stefan Frentzel, Florian Martin, Nikolai V. Ivanov, Manuel C. Peitsch, Julia Hoeng


Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland

Previous experimental setups shows the effects of e-liquids on cell viability (first layer), followed by investigating the potential mechanisms of toxicity elicited by e-liquids (second layer) and finally assessing the impacts of aerosols (third layer). In this present work shows how the three-layer framework is leveraged to evaluate the potential toxicity and biological effects of the MESH Classic Tobacco and Base e-liquids/aerosols compared with those of 3R4F CS.

 

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11. Aug. 2019

Exposure to aerosols from electronic cigarettes using the MESH™ technology has a reduced biological impact on bronchial epithelial cell cultures compared with exposure to cigarette smoke

Gordon Research Conference, Integration of Emerging Technologies in Mechanistic and Translational Toxicology,Andover, August 11–16, 2019

Albert Giralt, Florian Martin, Anita R. Iskandar, Alain Sewer, Laura Ortega Torres, AthanasiosKondylis, Patrice Leroy, Celine Merg, ShoaibMajeed, Emmanuel Guedj, Thomas Schneider, KeyurTrivedi, Stefan Frentzel, Nikolai V. Ivanov, Manuel C. Peitsch, Julia Hoeng


PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud5, CH-2000 Neuchâtel, Switzerland
 

In contrast to 3R4F CS exposure, exposure to IQOS MESH™ Classic Tobacco aerosols did not cause tissue damage or have an impact on ciliary beating functionality in bronchial epithelial cell cultures despite resulting in greater concentrations of deposited nicotine. Cultures exposed to IQOS MESH™ Classic Tobacco aerosols showed fewer changes in proteins involved in xenobiotic metabolism than those exposed to CS.

 

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12. Jun. 2019

Molecular Signature of Asthma-Enhanced Sensitivity to CuO Nanoparticle Aerosols from 3D Cell Model

DOI: 10.1021/acsnano.9b01823

Ingeborg Kooter1, Marit Ilves 2, Mariska Gröllers-Mulderij 1, Evert Duistermaat 3, Peter C. Tromp 1, Frieke Kuper 1, Pia Kinaret 4,5, Kai Savolainen 6, Dario Greco 4,5, Piia Karisola 2, Joseph Ndika 2, and Harri Alenius 2,7

1The Netherlands Organization for Applied Scientific Research, TNO, P.O. Box 80015, Utrecht 3584 CB, The Netherlands
2Human Microbiome Research, Faculty of Medicine, University of Helsinki, P.O. Box 21, Helsinki 00290, Finland
3Triskelion B.V., P.O. Box 844, Zeist 3704 HE, The Netherlands
4Faculty of Medicine and Life Sciences, University of Tampere, Tampere FI-33014, Finland
5Institute of Biotechnology, University of Helsinki, P.O. Box 56, Helsinki 00014, Finland
6Finnish Institute of Occupational Health, P.O. Box 40, Helsinki 00014, Finland
7Institute of Environmental Medicine, Karolinska Institutet, P.O. Box 210, Stockholm SE-17176, Sweden

3D human bronchial epithelial cells were cultured at the air−liquid interface that mimics relevant inhalatory exposure were exposed to aerosols of pristine (nCuO) and carboxylated (nCuOCOOH) copper oxide nanoparticles. This paper shows that the existence of asthma enhances sensitivity of the airways to nanoparticle aerosols, possibly as a combined result of a hyperactive airway and inefficient mucociliary clearance mechanisms in asthmatics. The test results are shown in cell viabilty (LDH), Inflammation (IL6, IL8, MCP1) and Transcroptomics.

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10. Mar. 2019

New Products at VITROCELL® User Group Meeting 2019

09 March 2019, Hilton Inner Harbour Hotel, Baltimore, USA

Following the VITROCELL® User Group Meeting 2018 in San Antonio, Texas, USA, international scientists from Europe, Japan, Korea and USA reconvened in March 2019.

The informal event organized into short presentations and posters was followed by open discussions. It was an excellent opportunity to discuss the latest developments of VITROCELL®, to exchange your experience in working with the equipment and to meet other fellow researchers.
The meeting took place prior to the international Society of Toxicology 58th Annual Meeting and ToxExpo, March 10 – 14, 2018, in Baltimore, USA - one of the largest international conferences related to toxicology.

Focus of the event was to share VITROCELL® activities since the last meeting, to exchange latest research results, to give an update on VITROCELL’s participation in major research programs as well as the presentation of new products for 2019.

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10. Mar. 2019

Exposure to an aerosol from a novel electronic cigarette using the MESH™ technology elicited reduced biological impacts than exposure to cigarette smoke on buccal and small airway epithelial cultures

Society of Toxicology, Annual Meeting 2019, Baltimore, MD, USA | 10-14 March

Anita R. Iskandar, Filippo Zanetti, Athanasios Kondylis, Florian Martin, Alain Sewer, Laura Ortega Torres, Shoaib Majeed, Sandro Steiner, Emmanuel Guedj, Celine Merg, Thomas Schneider, Keyur Trivedi, Stefan Frentzel, Nikolai V. Ivanov, Manuel C. Peitsch, Julia Hoeng


PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland

 

The impacts of an acute exposure to cigarette smoke (CS) and to aerosol from a novel electronic cigarette (EC) device using MESH™ technology were assessed using human organotypic buccal epithelial cultures and small airway epithelial cultures. A paired design was implemented: in parallel to the exposure to CS or EC aerosol, cultures were also exposed to air in the same exposure module. Tissue damage was not seen in cultures exposed to the IQOS MESH™ Classic Tobacco aerosol despite resulting in greater concentrations of deposited nicotine. In buccal cultures, CS and IQOS MESH™ Classic Tobacco aerosol elicited different infammatory response.

 

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5. Mar. 2019

A lower impact of an acute exposure to electronic cigarette aerosols than to cigarette smoke in human organotypic buccal and small airway cultures was demonstrated using systems toxicology assessment

DOI:10.1007/s11739-019-02055-x
Filippo Zanetti1, Athanasios Kondylis1, Florian Martin1, Patrice Leroy1, Shoaib Majeed1, Sandro Steiner1, Yang Xiang1, Laura Ortega Torres1, Keyur Trivedi1, Emmanuel Guedj1, Celine Merg1, Stefan Frentzel1, Nikolai V. Ivanov1, Utkarsh Doshi2, Kyeonghee Monica Lee2, Willie J. McKinneyJr2, Manuel C. Peitsch1, Julia Hoeng1

1 Philip Morris International R&D, Philip Morris Products S.A.NeuchâtelSwitzerland
2 Altria Client Services LLCRichmondUSA

Human organotypic buccal and small airway cultures were exposed in two independent exposure systems (Vitrocell® 24/48), one for 3R4F reference cigarette smoke and the other for e-cigarette aerosol exposures to summarize the exposure-induced impacts into four main cellular processes: the cell fate, cell proliferation, cell stress, and inflammatory process.

 

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6. Jun. 2018

Distribution of polymer-coated gold nanoparticles in a 3D lung model and indication of apoptosis after repeated exposure

DOI: 10.2217/nnm-2017-0358

Savvina Chortarea1,2, Kleanthis Fytianos1,3,4, Laura Rodriguez-Lorenzo1, Alke Petri-Fink1,5 & Barbara Rothen-Rutishauser1
1BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland
2Laboratory for Particles – Biology Interactions, Empa, Swiss Federal Laboratories for Materials, Science & Technology, St Gallen, Switzerland
3Department of Pulmonary Medicine, University of Bern, Bern, Switzerland
4Department of Clinical Research, University of Bern, Bern, Switzerland
5Department of Chemistry, University of Fribourg, Fribourg, Switzerland

The distribution and impact of aerosol-delivered functionalized AuNPs upon repeated administration were explored in a complex in vitro human lung epithelial tissue barrier model applying an air–liquid interface exposure approach. Nanoparticles were aerosolized using the Air-Liquid Interface system consisting of a nebulizer, an exposure and an incubation chamber connected to an air-flow system to provide optimum conditions for cell cultivation as well as a quartz crystal microbalance for online measurements of the NP dose deposited on the cells surface.

 

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