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, Neuchaˆtel, 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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27. Nov. 2021

Agglomeration State of Titanium-Dioxide (TiO2) Nanomaterials Influences the Dose Deposition and Cytotoxic Responses in Human Bronchial Epithelial Cells at the Air-Liquid Interface

https://doi.org/10.3390/nano11123226

Sivakumar Murugadoss 1, Sonja Mülhopt 2, Silvia Diabaté 3, Manosij Ghosh 1, Hanns-Rudolf Paur 2,
Dieter Stapf 2, Carsten Weiss 3, and Peter H. Hoet 1,

1 Laboratory of Toxicology, Unit of Environment and Health, Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium
2 Institute for Technical Chemistry, Karlsruhe Institute of Technology, 76021 Karlsruhe, Germany
3 Institute of Biological and Chemical Systems—Biological Information Processing, Karlsruhe Institute of Technology, 76021 Karlsruhe, Germany

 

In this study, they investigated the influence of agglomeration on the deposition and cytotoxic potency of TiO2 NMs at the ALI. Our results indicate that dose deposition and the cytotoxic potential are influenced by agglomeration, particularly for nano-sized TiO2 particles.

 

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27. Jun. 2021

Impact of Nanocomposite Combustion Aerosols on A549 Cells and a 3D Airway Model

https://doi.org/10.3390/nano11071685

Matthias Hufnagel 1, Nadine May 2, Johanna Wall 1, Nadja Wingert 3, Manuel Garcia-Käufer 3, Ali Arif 3, Christof Hübner 4, Markus Berger 5, Sonja Mülhopt 2, Werner Baumann 2, Frederik Weis 6, Tobias Krebs 5, Wolfgang Becker 4, Richard Gminski 3, Dieter Stapf 2, and Andrea Hartwig 1,


1 Department of Food Chemistry and Toxicology, Institute of Applied Biosciences, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany;
2 Institute for Technical Chemistry, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany; 
3 Institute for Infection Prevention and Hospital Epidemiology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany;
4 Fraunhofer Institute of Chemical Technology, 76327 Pfinztal, Germany; 
5 Vitrocell® Systems GmbH, 79183 Waldkirch, Germany; 
6 Palas GmbH, 76229 Karlsruhe, Germany; 

 

This study was the first to investigate the toxicological effects of well characterized aerosols released during combustion of thermoplastic nanocomposites using an air–liquid interface exposure system. Even though studies on the toxicological potential of combustion-generated particulate matter as well as VOCs have been published, none of them was designed to investigate the effect of the native aerosol using appropriate realistic lung cell culture models. In the current study we investigated the combustion behavior of PE-based nanocomposites on a lab-scale burner. As nanoscaled fillers TiO2 NP, CuO NP, as well as CNT were chosen for this study, with TiO2 NP representing a commonly used insoluble and inert nanomaterial, CuO NP as a known in vitro cyto- as well as genotoxic nanomaterial, and CNT as a fiber-shaped nanomaterial.

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21. Jun. 2021

In vitro hazard characterization of simulated aircraft cabin bleed-air contamination in lung models using an air-liquid interface (ALI) exposure system

https://doi.org/10.1016/j.envint.2021.106718

Rui-Wen He a,b, Marc M.G. Houtzager c, W.P. Jongeneel a, Remco H.S. Westerink b, Flemming R. Cassee a,b

a National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, the Netherlands
b Institute for Risk Assessment Sciences (IRAS), Toxicology Division, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80177, 3508 TD Utrecht, the Netherlands
c The Netherlands Organisation for Applied Scientific Research, TNO, P.O. Box 80015, 3508 TA Utrecht, the Netherlands

 

This unique experimental “Mini-BACS + AES” setup is able to provide steady conditions to perform in vitro exposure under ALI conditions to aircraft engine oil and hydraulic fluid fumes, generated at respectively 350 ◦C and 200 ◦C. Exposure of the Calu-3 monoculture and Calu-3 + MDM co-culture lung cell models to high levels of aircraft engine oil and hydraulic fluid fumes under ALI conditions can reduce TEER and viabilities of the cells, induce cytotoxicity, and increase production of proinflammatory cytokines. Hydraulic fluid fumes are more toxic than engine oil fumes on the mass concentration of fume basis, which may be related to higher abundance of OPs and smaller particle size of hydraulic fluid fumes. The toxicological data clearly reflect the potential health risks during fume events in aircraft cabins.

 

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15. Jun. 2021

VITROCELL® Cloud Alpha - A Family of Exposure Systems Suitable for Nebulized Solutions and Suspensions

Poster LIVe 2021 Kongress, 15th June 2021

Patrick Weindl, Heidi Ortolf-Wahl, Tobias Krebs

VITROCELL Systems GmbH, 79183 Waldkirch, Germany

 

Optimal Solution for Everyday Experiments  at the Air/Liquid Interface
The VITROCELL® Cloud Alpha series is our newest innovation and presents a great leap forward in automated exposure of cell cultures. It combines reliable exposure of cell cultures from the respiratory tract with ease of use. The series comprises the Cloud Alpha 6, - 12, - 96 and Cloud Alpha MAX – they represent an optimal solution for everyday experiments at the Air/Liquid Interface using 6-well, 12-well, 24-well or 96-sized inserts. We have run extensive tests to ensure the Cloud Alpha series devices match our standards in terms of the established characteristics for Cloud principle exposure devices: Deposition Efficiency, Spatial Deposition and Repeatability.
 

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2. Jun. 2021

Development of a standardized in vitro approach to evaluate microphysical, chemical, and toxicological properties of combustion-derived fine and ultrafine particles

https://doi.org/10.1016/j.jes.2021.06.001

Ana Teresa Juarez-Facio 1, Clément Castilla 2, Cécile Corbière 1, Hélène Lavanant 2, Carlos Afonso 2, Christophe Morin 2, Nadine Merlet-Machour 2, Laurence Chevalier 3, Jean-Marie Vaugeois 1, Jérôme Yon 4, Christelle Monteil 1,
1Normandie Univ, UNIROUEN, UNICAEN ABTE, 76000 Rouen, France
2Normandie Univ, UNIROUEN, INSA Rouen, CNRS, COBRA, 76000 Rouen, France
3Normandie Univ, UNIROUEN, INSA Rouen, CNRS, GPM-UMR6634, 76000 Rouen, France
4Normandie Univ, UNIROUEN, INSA Rouen, CNRS, CORIA, 76000 Rouen, France

 

The present study illustrate a methodological approach which allows comparing, in an original and innovative way, the physical, chemical, and toxicological properties of different fine and ultrafine particles. In this study, two different operating conditions were used to obtain model particles containing either high (CAST3) or low (CAST1) organic contents, and exposed differentiated NHBE cells “on-line” at the air-liquid interface to be closer to realistic conditions.

 

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20. Apr. 2021

An In Vitro Air-Liquid Interface Inhalation Platform for Petroleum Substances and Constituents

DOI: 10.14573/altex.2010211 


Sandra Verstraelen1, An Jacobs1, Jo Van Laer1, Karen Hollanders1, Masha Van Deun2, Diane Bertels2, Rob Brabers1, Hilda Witters1, Sylvie Remy1,3, Lieve Geerts1, Lize Deferme4 and Evelien Frijns1
1VITO NV (Flemish Institute for Technological Research), Unit HEALTH, Mol, Belgium; 
2VITO NV, Unit Separation and Conversion Technology (SCT), Mol, Belgium; 
3University of Antwerp, Department of Biomedical Sciences, Antwerp, Belgium; 
4ExxonMobil Petroleum and Chemical BV, Machelen, Belgium
 

This pilot study exposed a frequently used in vitro model (A549 cells) at the ALI to assess inhalation toxicity of the single compound EB. Experimental conditions using the VITROCELL® 24/48 exposure system were optimized to achieve a (low) delivery efficiency that resulted in dose-dependent biological changes. The data demonstrate consistency in effect levels when comparing cell viability in the ALI experiments with known in vivo non-lethal effects in humans. It can be concluded that QIVIVE from in vitro air concentrations applied for testing cell viability to in vivo air concentrations may be a promising method for screening for acute inhalation toxicity. 

 

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3. Mar. 2021

Vitrocell® Leak Tester

Must-have device for aerosol research – easy and efficient leak detection

Regular leak tests are mandatory in aerosol research. A leak caused by a forgotten connection or defective o-ring may have a significant influence on the aerosol exposure process. We recommend to carry out a leak test prior to the experiment and as part of cleaning or service routine.

VITROCELL Application Note

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15. Feb. 2021

Impact of Sea Breeze Dynamics on Atmospheric Pollutants and Their Toxicity in Industrial and Urban Coastal Environments

doi:10.3390/rs12040648

Patrick Augustin 1, Sylvain Billet 2 , Suzanne Crumeyrolle 3, Karine Deboudt 1, Elsa Dieudonné 1 , Pascal Flament 1 , Marc Fourmentin 1 , Sarah Guilbaud 1, Benjamin Hanoune 4 , Yann Landkocz 2, Clémence Méausoone 2, Sayahnya Roy 5, François G. Schmitt 5, Alexei Sentchev 5 and Anton Sokolov 1
1 Univ. Littoral Côte d’Opale, UR 4493—LPCA—Laboratoire de Physico-Chimie de l’Atmosphère, 59140 Dunkerque, France;
2 Univ. Littoral Côte d’Opale, SFR Condorcet FR CNRS 3417, UR 4492—UCEiV—Unité de Chimie Environnementale et Interactions sur le Vivant, 59140 Dunkerque, France; 
3 Univ. Lille, CNRS, UMR 8518—LOA—Laboratoire d’Optique Atmosphérique, 59000 Lille, France;
4 Univ. Lille, CNRS, UMR 8522—PC2A—Physico-Chimie des Processus de Combustion et de l’Atmosphère, 59000 Lille, France; 
5 Univ. Lille, Univ. Littoral Côte d’Opale, CNRS, UMR 8187—LOG—Laboratoire d’Océanologie et de Géosciences, F 62930 Wimereux, France; 

 

An atmospheric mobile unit was implemented during a field campaign performed at a representative site of urbanized and industrialized coastal environment of the North Sea (Northern France), to study the impact of sea breeze dynamics on aerosol properties, and especially their toxicity. This unit combined aerosol samplers, two scanning lidars (Doppler and elastic), two aerosol particle sizers and an air-liquid interface (ALI, Vitrocell) in vitro cell exposure device. This study is one of the first to bring cell cultures into the field to evaluate the harmfulness of a real environmental compartment. Atmospheric toxicity in the presence or absence of sea breeze was demonstrated in human bronchial cells exposed in the field using an ALI exposure system. The study showed the sensitivity of the developed device to discriminate the mechanisms of toxic action activated when exposed to different atmospheres.

 

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29. Jan. 2021

A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions

DOI: 10.3389/fbioe.2021.616830 


Ali Doryab 1,2, Mehmet Berat Taskin 3, Philipp Stahlhut 3, Andreas Schröppel 1,2, Sezer Orak 1,2, Carola Voss 1,2, Arti Ahluwalia 4,5, Markus Rehberg 1,2, Anne Hilgendorff 1,2,6, Tobias Stöger 1,2, Jürgen Groll 3 and Otmar Schmid 1,2

1 Comprehensive Pneumology Center Munich, Member of the German Center for Lung Research, Munich, Germany,
2 Helmholtz Zentrum München—German Research Center for Environmental Health, Institute of Lung Biology and Disease, Munich, Germany, 
3 Department of Functional Materials in Medicine and Dentistry, Bavarian Polymer Institute, University of Würzburg, Würzburg, Germany, 
4 Research Center “E. Piaggio”, University of Pisa, Pisa, Italy, 
5 Department of Information Engineering, University of Pisa, Pisa, Italy, 
6 Center for Comprehensive Developmental Care (CDeCLMU), Dr. von Haunersches Children’s Hospital University, Hospital of the Ludwig-Maximilians University, Munich, Germany
 

We have recently introduced a novel porous and elastic membrane for in vitro cell-stretch models of the lung cultured under ALI conditions (Doryab et al., 2020). This innovative hybrid biphasic membrane, henceforth referred to as Biphasic Elastic Thin for Air-liquid culture conditions (BETA) membrane, was developed to optimize membrane characteristics for  the two phases of cell-stretch experiments under ALI conditions, namely the initial cell seeding, attachment and growth phase under submerged cell culture conditions  (phase  I)  followed  by an ALI acclimatization and cell-stretch phase at the ALI (phase II). This patented aerosol-cell exposure unit has recently been made  commercially  available  as  VITROCELL® Cloud  MAX.

 

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