Advanced in vitro exposure systems.

25. Jun. 2020

Novel TEM Grid holders for dose determination of airborne particles during in vitro Exposure at the air / liquid interface

The assessment of toxicological effects of airborne particles to the human organism is of major importance in disease research. The presence of nano and ultrafine particles can be found both in indoor and outdoor atmospheres which include workplaces and living areas. Over the last years, the degree of contribution to diseases of such particles is analyzed ever more frequent by the use of in vitro methods. The required equipment for these studies consisting of aerosol generation and exposure systems are nowadays developed more and more to proven levels.

VITROCELL Application Note.

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13. May. 2020

An Air-liquid Interface Bronchial Epithelial Model for Realistic, Repeated Inhalation Exposure to Airborne Particles for Toxicity Testing

DOI:10.3791/61210 


Hedwig M. Braakhuis1, Ruiwen He1,2, Rob J. Vandebriel1, Eric R. Gremmer1, Edwin Zwart1, Jolanda P. Vermeulen1, Paul Fokkens1, John Boere1, Ilse Gosens1, Flemming R. Cassee1,2 
1National Institute for Public Health and the Environment (RIVM) 
2Institute for Risk Assessment Sciences (IRAS) 


This article provides a method for culturing and exposing the human bronchial epithelial cell line Calu-37 at the Air-liquid Interface that mimics realistic, repeated inhalation exposure conditions that can be used for toxicity testing. By applying a continuous airflow using the Automated Exposure System, the cell model can be exposed to a low concentration of particles over a longer time period, reflecting realistic exposure conditions. Characteristics of both the cell model and of  the exposure system are essential for achieving a realistic inhalation exposure model that can be used for repeated exposures. 

 

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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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15. Jan. 2020

Use of in vitro 3D tissue models in genotoxicity testing: Strategic fit, validation status and way forward.

Report of the working group from the 7th International Workshop on Genotoxicity Testing (IWGT)

https://doi.org/10.1016/j.mrgentox.2020.503135

Authors
StefanPfuhlera, Janvan Benthemb, RodgerCurrenc, Shareen H.Doakd, MariaDusinskae, MakotoHayashif, Robert H.Heflichg, DarrenKiddh, DavidKirklandi, YangLuanj, GladysOuedraogok, KerstinReisingerl, ToshioSofunim, Frédériquevan Ackern, YingYango, RaffaellaCorvip
a Procter and Gamble, Mason Business Centre, Mason, OH, USA
b National Institute for Public Health and the Environment, Centre for Health Protection, Bilthoven, the Netherlands
c Institute for In Vitro Sciences, Inc., Gaithersburg, MD, USA
d Swansea University Medical School, Singleton Park, Swansea, SA2 8PP, Wales, UK
e Health Effects Laboratory, Department of Environmental Chemistry, NILU-Norwegian Institute for Air Research, Kjeller, Norway
f makoto international consulting, Ebina, Japan
g U.S. Food and Drug Administration/National Center for Toxicological Research, Jefferson, AR, USA
h Covance Laboratories Ltd, Otley Road, Harrogate, HG3 1PY, UK
i Kirkland Consulting, PO Box 79, Tadcaster, LS24 0AS, UK
j School of Public Health, Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China
k L’Oréal R&I, Aulnay-sous-bois, France
l Henkel AG & Co KGaA, Duesseldorf, Germany
m Formerly National Institute of Health Sciences, Tokyo, Japan
n Triskelion B.V., Zeist, the Netherlands
o Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, PR China
p European Commission, Joint Research Centre (JRC), Ispra, Italy

 

Highlights
• Extensive progress made in development of 3D organ-based genotoxicity assays.
• 3D culture models represent major exposure routes: dermal, oral, inhalation.
• The 3D skin comet and MN assays are considered mature and sufficiently validated.
• Liver and airway model-based genotoxicity assays show promise but are at early stage.<

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1. Nov. 2019

Electronic Cigarette Vapor With Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors

DOI: 10.1164/rccm.201811-2087OC


Samuel Chung 1 2, Nathalie Baumlin 1 2, John S Dennis 1 2, Robert Moore 2, Sebastian F Salathe 2, Phillip L Whitney 2, Juan Sabater 3, William M Abraham 3, Michael D Kim 1 2, Matthias Salathe 1 2
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
2Division of Pulmonary, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, Florida; and.
3Department of Research, Mount Sinai Medical Center, Miami Beach, Florida.
 

The transient receptor potential ankyrin 1 (TRPA1) is a molecular target for vape effects due to its expression in airway epithelia and its reported gating by nicotine, reactive oxidants, and flavors, especially cinnamaldehyde. To test whether nicotine had effects independent of other e-cig vapor constituents, the Vitrocell® CLOUD exposure system was utilized to nebulize fixed nicotine doses onto the apical surface of ALI cultures. A549 cell cultures were exposed to nicotine containing e-cig vapor, produced by the VC-1 smoke exposure robot, in the air-liquid interface.

 

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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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