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Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors

Influenza A virus (IAV) continuously causes epidemics and claims numerous lives every year. The available treatment options are insufficient and the limited pertinence of animal models for human IAV infections is hampering the development of new therapeutics. Bioprinted tissue models support studyin...

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Autores principales: Berg, Johanna, Weber, Zia, Fechler-Bitteti, Mona, Hocke, Andreas C., Hippenstiel, Stefan, Elomaa, Laura, Weinhart, Marie, Kurreck, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402746/
https://www.ncbi.nlm.nih.gov/pubmed/34452455
http://dx.doi.org/10.3390/v13081590
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author Berg, Johanna
Weber, Zia
Fechler-Bitteti, Mona
Hocke, Andreas C.
Hippenstiel, Stefan
Elomaa, Laura
Weinhart, Marie
Kurreck, Jens
author_facet Berg, Johanna
Weber, Zia
Fechler-Bitteti, Mona
Hocke, Andreas C.
Hippenstiel, Stefan
Elomaa, Laura
Weinhart, Marie
Kurreck, Jens
author_sort Berg, Johanna
collection PubMed
description Influenza A virus (IAV) continuously causes epidemics and claims numerous lives every year. The available treatment options are insufficient and the limited pertinence of animal models for human IAV infections is hampering the development of new therapeutics. Bioprinted tissue models support studying pathogenic mechanisms and pathogen-host interactions in a human micro tissue environment. Here, we describe a human lung model, which consisted of a bioprinted base of primary human lung fibroblasts together with monocytic THP-1 cells, on top of which alveolar epithelial A549 cells were printed. Cells were embedded in a hydrogel consisting of alginate, gelatin and collagen. These constructs were kept in long-term culture for 35 days and their viability, expression of specific cell markers and general rheological parameters were analyzed. When the models were challenged with a combination of the bacterial toxins LPS and ATP, a release of the proinflammatory cytokines IL-1β and IL-8 was observed, confirming that the model can generate an immune response. In virus inhibition assays with the bioprinted lung model, the replication of a seasonal IAV strain was restricted by treatment with an antiviral agent in a dose-dependent manner. The printed lung construct provides an alveolar model to investigate pulmonary pathogenic biology and to support development of new therapeutics not only for IAV, but also for other viruses.
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spelling pubmed-84027462021-08-29 Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors Berg, Johanna Weber, Zia Fechler-Bitteti, Mona Hocke, Andreas C. Hippenstiel, Stefan Elomaa, Laura Weinhart, Marie Kurreck, Jens Viruses Article Influenza A virus (IAV) continuously causes epidemics and claims numerous lives every year. The available treatment options are insufficient and the limited pertinence of animal models for human IAV infections is hampering the development of new therapeutics. Bioprinted tissue models support studying pathogenic mechanisms and pathogen-host interactions in a human micro tissue environment. Here, we describe a human lung model, which consisted of a bioprinted base of primary human lung fibroblasts together with monocytic THP-1 cells, on top of which alveolar epithelial A549 cells were printed. Cells were embedded in a hydrogel consisting of alginate, gelatin and collagen. These constructs were kept in long-term culture for 35 days and their viability, expression of specific cell markers and general rheological parameters were analyzed. When the models were challenged with a combination of the bacterial toxins LPS and ATP, a release of the proinflammatory cytokines IL-1β and IL-8 was observed, confirming that the model can generate an immune response. In virus inhibition assays with the bioprinted lung model, the replication of a seasonal IAV strain was restricted by treatment with an antiviral agent in a dose-dependent manner. The printed lung construct provides an alveolar model to investigate pulmonary pathogenic biology and to support development of new therapeutics not only for IAV, but also for other viruses. MDPI 2021-08-11 /pmc/articles/PMC8402746/ /pubmed/34452455 http://dx.doi.org/10.3390/v13081590 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Berg, Johanna
Weber, Zia
Fechler-Bitteti, Mona
Hocke, Andreas C.
Hippenstiel, Stefan
Elomaa, Laura
Weinhart, Marie
Kurreck, Jens
Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors
title Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors
title_full Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors
title_fullStr Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors
title_full_unstemmed Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors
title_short Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors
title_sort bioprinted multi-cell type lung model for the study of viral inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402746/
https://www.ncbi.nlm.nih.gov/pubmed/34452455
http://dx.doi.org/10.3390/v13081590
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