Advanced in vitro exposure systems.

18. Nov. 2022

Rescue of Ciliary Function in Cell-based Primary Ciliary Dyskinesia Models using Nebulized, LNP-formulated mRNA

Rumpa B. Bhattacharjee1, Mirko Hennig1, Daniella Ishimaru1, David Liston1, Jackson K. Eby2, Christian C. Corona1, Ishita Agarwal1 Jade E. Casillas1, Shohan Molla1, Maninder S. Sidhu1, Julia Poniatowski1, Sierra R. Comini1, Ally Ashworth1, Xueliang Yu2, Peiyang Gao2, Harriet E. Lister1, Omid Mousa1, Hannah L. Golliher3, Patrick R. Sears3, Weining Yin3, Michael J. Torres2, Daniel J. Siegwart4, Vladimir G. Kharitonov1, Lawrence E. Ostrowski3, David J. Lockhart1, Brandon A. Wustman1
1 ReCode Therapeutics, Inc., Menlo Park, CA, 
2 ReCode Therapeutics, Inc., Dallas, TX,
3 Dept of Cell Biology and Physiology, UNC-Chapel Hill, NC, 4UT Southwestern Medical Center, Dallas, TX

 

Rescue of Ciliary Function in Cell-based Primary Ciliary Dyskinesia Models using Nebulized, LNP-formulated mRNA ReCode Therapeutics is developing an mRNA-based therapy for the treatment of PCD caused by mutations in DNAI1. The DNAI1 mRNA is sequence optimized and formulated in a proprietary SORT lipid nanoparticle (LNP). The LNP formulated mRNA is nebulized and delivered as an aerosol directly into the airway by using a VITROCELL® Cloud 12. Using knockdown human bronchial epithelial (hBE) cultures and knockout mouse tracheal cultures we show that ReCode’s LNP can restore ciliary activity.

 

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14. Nov. 2022

An inter-laboratory effort to harmonize the cell-delivered in vitro dose of aerosolized materials

https://doi.org/10.1016/j.impact.2022.100439
Anne Bannuscher a, Otmar Schmid b,c, Barbara Drasler a, Alain Rohrbasser a, Hedwig M. Braakhuis d, Kirsty Meldrum e, Edwin P. Zwart d, Eric R. Gremmer d, Barbara Birk f, Manuel Rissel f, Robert Landsiedel f,g, Elisa Moschini h, Stephen J. Evans e, Pramod Kumar b,c, Sezer Orak b,c, Ali Doryab b,c, Johanna Samulin Erdem i, Tommaso Serchi h, Rob J. Vandebriel d, Flemming R. Cassee d,j, Shareen H. Doak e, Alke Petri-Fink a, Shanbeh Zienolddiny i, Martin J. D. Clift e, Barbara Rothen-Rutishauser a,
a Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, Switzerland
b Comprehensive Pneumology Center (CPC-M), Helmholtz Zentrum München - Member of the German Center for Lung Research (DZL), Max-Lebsche-Platz 31, 81377 Munich, Germany
c Institute of Lung Health and Immunity, Helmholtz Zentrum München – German Research Center for Environmental Health, 85764 Neuherberg, Germany
d National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720, BA, Bilthoven, the Netherlands
e In Vitro Toxicology Group, Faculty of Medicine, Health and Life Sciences, Medical School, Institute of Life Sciences, Centre for NanoHealth, Swansea University, Singleton Campus, Wales SA2 8PP, UK
f BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen am Rhein, Germany
g Free University of Berlin, Pharmacy, Pharmacology and Toxicology, 14195 Berlin, Germany.
h Department of Environmental Research and Innovation, Luxembourg Institute of Science and Technology (LIST), 41 rue du Brill, L4422 Belvaux, Grand-Duchy of Luxembourg, Luxembourg
i National Institute of Occupational Health (STAMI), N-0033 Oslo, Norway
j Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands

Harmonization of SOP for (nano)material aerosolization using the VITROCELL® Cloud12.
Inter-laboratory comparison among seven different laboratories in Europe.

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30. Sep. 2022

Dynamic Fluid Flow Exacerbates the (Pro-)Inflammatory Effects of Aerosolised Engineered Nanomaterials In Vitro

https://doi.org/10.3390/nano12193431

Kirsty Meldrum, Joana A. Moura, Shareen H. Doak and Martin J. D. Clift
In Vitro Toxicology Group, Swansea University Medical School, Swansea University, Wales SA2 8PP, UK
 

The aim of this study was to develop further an established static in vitro model used to test ENP aerosol toxicology to incorporate fluid-flow dynamics. This was achieved by implementing the QuasiVivoTM system with a characterised A459_dTHP-1 coculture exposed in the Vitrocell Cloud12 to different particle samples at the ALI. 

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29. Jul. 2022

Advanced Respiratory Models for Hazard Assessment of Nanomaterials—Performance of Mono-, Co- and Tricultures

https://doi.org/10.3390/nano12152609

Laura Maria Azzurra Camassa 1, Elisabeth Elje 2,3, Espen Mariussen 2,4, Eleonora Marta Longhin 2, Maria Dusinska 2, Shan Zienolddiny-Narui 1, and Elise Rundén-Pran 2
1 National Institute of Occupational Health in Norway, 0033 Oslo, Norway
2 NILU—Norwegian Institute for Air Research, 2027 Kjeller, Norway
3 Institute of Basic Medical Sciences, Department of Molecular Medicine, University of Oslo, 0372 Oslo, Norway
4 Norwegian Institute of Public Health, FHI, 0456 Oslo, Norway
 

This study aimed at testing the robustness and sensitivity, characterizing, and optimizing an advanced respiratory model built on human alveolar epithelial A549 cells and evaluating its response to aerosol exposure of silver NM-300K. In more detail, we compared the responses of A549 cells cultured at the ALI in the VITROCELL® 6 Cloud system in monoculture, in coculture with EA.hy926 cells, and in triculture with EA.hy926 cells and dTHP-1, and performed an interlaboratory trial across two laboratories.

 

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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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4. Apr. 2022

Product News 04-1/2022

VITROCELL® Cloud Alpha PowerVent 

Increase of nebulizations and evacuation of residual gaseous compounds

A typical Cloud exposure allows 3 consecutive nebulizations. The PowerVent option enables an increase of the dose by adding further nebulizations. After each nebulization the humidity is removed by a short venting period before starting the new one. The venting function can be edited in the software. The PowerVent unit is delivered ready-to-use with an integrated vacuum pump.

VITROCELL® Cloud Alpha PowerVent  (PDF)

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3. Feb. 2022

Product News 02-1/2022

VITROCELL® Cloud Advanced Nebulizer

For liquid droplet sizes 9 – 12 μm with diffusor

Certain chemicals or formulations, for example nasal sprays, often have larger particle sizes than the mesh size of standard nebulizers (4.0 – 6.0 μm). The VITROCELL Cloud Advanced Nebulizer is enlarging the application areas of Cloud Exposure Systems. This special type offers the possibility to produce an aerosol containing particles in the range of 9.0 – 12.0 μm.
Our patented Cloud diffusor ensures a homogeneous distribution of even the larger droplet sizes in the Cloud Exposure Chamber. To avoid effects from larger droplet formations it has an integrated drain channel.

VITROCELL® Cloud Advanced Nebulizer  (PDF)

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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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12. Nov. 2021

Product News 11/2021

VITROCELL® S-QCM

Improved Sensor for High Precision Real-Time Dose Monitoring

The VITROCELL® sQCM 12 is the next step in the evolution of dosimetry methods in cell culture exposure systems. It simplifies the usage of conventional Quartz Crystal Microbalances suitable for VITROCELL® 12 modules while maintaining the working principle, precision and accuracy of the balances you’re used to.

VITROCELL® S-QCM  (PDF)

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