Advanced in vitro exposure systems.

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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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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11. Nov. 2020

Exposure of cellulose nanocrystals on human lung cells at the air-liquid-interface

Best poster prize award at the Euro 2020 OpenTox Virtual Conference on September 21-25, 2020.

Michelle Hesler1, Annika Kittel1, Stephan Dähnhardt-Pfeiffer2, Christoph Metzger3, Christine Herrmann3, Marielle Fink4, Heiko Briesen3, Tobias Krebs4, Hagen von Briesen1, Sylvia Wagner1, Yvonne Kohl1
1 Fraunhofer Institut für Biomedizinische Technik IBMT, Sulzbach, Germany, 
2 Microscopy Services Dähnhardt GmbH, Flintbek, Germany, 
3 Lehrstuhl für Systemverfahrenstechnik, Technische Universität München, Freising, Germany, 
4 VITROCELL Systems GmbH, Fabrik Sonntag 3, Waldkirch, Germany

 

- In vitro aerosol exposure studies were performed with an air-liquid-interface (ALI)-lung model consisting of A549 (epithelial cells), EA.hy926 (endothelial cells) and THP-1 (macrophages) cells.
- Two different types of CNC extracted from α-cellulose (CNC-W) and pulp (CNC-G) by sulfuric acid hydrolysis were studied in a concentration of 100 μg/ml applied as aerosols with VITROCELL® Cloud system.
- Single and multiple exposure with and without a 24 h regeneration phase were compared.
- Endpoints of the study: Cell viability, ROS generation and DNA damage.

 

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31. Oct. 2020

Optimization of an air-liquid interface in vitro cell co-culture model to estimate the hazard of aerosol exposures

https://doi.org/10.1016/j.jaerosci.2020.105703

 

Rui-Wen He a,b, Hedwig M. Braakhuis a, Rob J. Vandebriel a, Yvonne C.M. Staal a, Eric R. Gremmer a, Paul H.B. Fokkens a, Claudia Kemp a, Jolanda Vermeulen 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, Utrecht University, P.O. Box 80178, 3508, TD, Utrecht, the Netherlands

 

The results demonstrate the substantial differences in cellular responses including cell morphology, TEER changes, and cytotoxicity for epithelial mono-culture of 16HBE, Calu-3, H292 and BEAS-2B cells as well as the macrophage/epithelial cell co-culture models under ALI conditions. With the optimization of the co-culture procedure at the ALI, the cell co-culture models showed epithelial monolayer integrity, and increased sensitivity in inflammatory responses to LPS exposure, with the Calu-3 + MDM model giving the strongest responses.

 

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29. Sep. 2020

Invited review: human air-liquid-interface organotypic airway tissue models derived from primary tracheobronchial epithelial cells—overview and perspectives

https://doi.org/10.1007/s11626-020-00517-7


Xuefei Cao1, Jayme P. Coyle2, Rui Xiong1, Yiying Wang1, Robert H. Heflich1, Baiping Ren1, William M. Gwinn3, Patrick Hayden4, Liying Rojanasakul2

1 Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd., AR Jefferson, USA
2 Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers forDisease Control and Prevention,Morgantown,WV, USA
3 Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Durham, NC, USA
4 BioSurfaces Inc., Ashland, MA, USA


One important element for validating any new assay for making regulatory decisions is determining its performance relative to an accepted standard. Conducting in vivo inhalation toxicity studies using whole-body or nose-only exposure systems is expensive and time-consuming and typically requires a large number of animals. The goal of using alternative methods, like human in vitro ALI airway cultures, ultimately is to replace inhalation toxicity testing in animals with in vitro approaches. Transition from animal- to human-based models is ultimately expected to lead to faster and better predictive toxicity assessments and therapeutic development at lower cost.  This study shows the development and validation of alternative in vitro methods for acute toxicity testing, including acute inhalation toxicity testing.
 

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28. Sep. 2020

NanoCELL - Comprehensive characterization and human toxicological assessment of cellulose nanocrystals along their life cycle for reliable risk assessment

Yvonne Kohl1, Roland Drexel2, Christine Herrmann3, Stephan Dähnhardt-Pfeiffer4, Siegfried Fürtauer5, Michelle Hesler1, Christoph Metzger3, Marielle Fink6, Dominik Selzer7, Thorsten Lehr7, Tobias Krebs6, Sven van Lengen8, Sylvia Wagner1, Hagen von Briesen1, Felix Grimm9, Petra Weißhaupt10, Heiko Briesen3, Florian Meier2


1Fraunhofer-Institut für Biomedizinische Technik IBMT, Sulzbach, Germany; 
2Postnova Analytics GmbH, Landsberg, Germany, 
3Technische Universität München, Lehrstuhl für Systemverfahrenstechnik, Freising, Germany 
4Microscopy Services Dähnhardt GmbH, Flintbek, Germany
5Fraunhofer-Institut für Verfahrenstechnik und Verpackung IVV, Freising, Germany
6VITROCELL Systems GmbH, Waldkirch, Germany
7Universität des Saarlands, Klinische Pharmazie, Saarbrücken, Germany 
8GRÜNPERGA Papier GmbH, Grünhainichen, Germany 
9INFIANA Germany GmbH & Co. KG, Forchheim, Germany
10Umweltbundesamt, Dessau-Roßlau, Germany

 

This poster shows the hazard studies on the effect of oral and pulmonary CNC uptake. Therefore a miniaturized cloud exposure system has been developed to create an in vitro model simulating the lung and the GI tract.

 

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16. Sep. 2020

Quartz crystal microbalances (QCM) are suitable for real-time dosimetry in nanotoxicological studies using VITROCELL®Cloud cell exposure systems

https://doi.org/10.1186/s12989-020-00376-w


Yaobo Ding1,2 , Patrick Weindl1,2,3, Anke-Gabriele Lenz1,2, Paula Mayer1,2, Tobias Krebs3 and Otmar Schmid1,2
1Institute of Lung Biology and Disease, Helmholtz Zentrum München, 85764 Neuherberg, Germany
2Comprehensive Pneumology Center, Munich (CPC-M) - Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
3VITROCELL Systems GmbH, 79183 Waldkirch, Germany.

 

This study provides evidence that QCMs are suitable for real-time dosimetry in particle toxicology studies with cell cultures under air-liquid interface conditions. An experimental method for determination of LoD (lower limit of detection), accuracy and precision of QCMs using a fluorescent tracer (fluorescein salt) was presented and applied to the QCMs integrated in the VITROCELL® Cloud 6 and Cloud 12 aerosol-cell exposure systems.

 

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27. Aug. 2020

Comparative anti-inflammatory effect of curcumin at air-liquid interface and submerged conditions using lipopolysaccharide stimulated human lung epithelial A549 cells

https://doi.org/10.1016/j.pupt.2020.101939


Yue Hu a,b,c, Yunhua Sheng c,e, Xiaoli Ji c,e, Ping Liu c,e, Liming Tang c,e, Gang Chen a,Guiliang Chen b,d,
a School of Pharmacy, Fudan University, Shanghai, China
b China State Institute of Pharmaceutical Industry, Shanghai, China
c Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai, China
d Shanghai Center for Drug Evaluation and Inspection, Shanghai, China
e NMPA Key Laboratory for Quality Analysis of Chemical Drug Preparations, Shanghai, China

 

In this study, the ALICE-CLOUD system was used as an easy-to-use and dosimetrically accurate ALI system for efficient delivery of the curcumin aerosol to the cells. It has been used to assess not only the respiratory effect of nanoparticles and chemicals after single or repeated exposure, but also the biokinetics of aerosolized drugs. Conventional ALI systems were mainly developed for toxicity study of inhaled substances. Compared with other systems, the ALICE-CLOUD system is not only technically simpler, easier to handle, but also has higher drug delivery efficiency and shorter exposure time. The short exposure time of the ALICE-CLOUD system was similar to the actual administration pattern of the inhaled drugs, which is suitable for preclinical development of aerosolized drugs and cellular response mechanisms for inhalation therapy.

 

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24. Aug. 2020

Product News 08/2020

VITROCELL® Cloud Alpha 96

96-well Air/Liquid Interface (ALI) exposure. For reliable high throughput testing of cell cultures.

The VITROCELL® Cloud Alpha 96 is our newest innovation and presents a great leap forward in automated exposure of cell cultures. It combines high throughput testing with ease of use. The development is based on the well-known and frequently published VITROCELL® Cloud formats (6-, 12- and 24-well). It’s functionality enables fully automated processes with an all-in-one control unit. Everyday experiments at the air/liquid interface have never been easier.

VITROCELL® Cloud Alpha 96

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27. Jul. 2020

An In Vitro Lung System to Assess the Proinflammatory Hazard of Carbon Nanotube Aerosols

doi:10.3390/ijms21155335


Hana Barosova 1,2 , Bedia Begum Karakocak 1 , Dedy Septiadi 1 , Alke Petri-Fink 1,3, Vicki Stone 4 and Barbara Rothen-Rutishauser 1,
1 BioNanomaterials Group, Adolphe Merkle Institute, University of Fribourg, 1700 Fribourg, 
2 Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague, Czech Republic
3 Department of Chemistry, University of Fribourg, 1700 Fribourg, Switzerland
4 Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, UK


The in vitro co-culture model consisting of three human cell lines were exposed at the ALI using the VITROCELL® Cloud system, equiped with QCM allowing to measure and record the deposited dose online. The nebulizer was ideal for the aerosols to suffciently mix within the entire chamber, hence resulting in uniform droplet deposition. This study shows, that this model is not limited to testing potentially hazardous nanomaterials to human cell line co-culture models.

 

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