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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/8/1590 |
| _version_ | 1797521813314469888 |
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| author | Johanna Berg Zia Weber Mona Fechler-Bitteti Andreas C. Hocke Stefan Hippenstiel Laura Elomaa Marie Weinhart Jens Kurreck |
| author_facet | Johanna Berg Zia Weber Mona Fechler-Bitteti Andreas C. Hocke Stefan Hippenstiel Laura Elomaa Marie Weinhart Jens Kurreck |
| author_sort | Johanna Berg |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T08:17:53Z |
| format | Article |
| id | doaj.art-b8db7bb837414279bf01095f171007f9 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T08:17:53Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-b8db7bb837414279bf01095f171007f92023-11-22T10:11:46ZengMDPI AGViruses1999-49152021-08-01138159010.3390/v13081590Bioprinted Multi-Cell Type Lung Model for the Study of Viral InhibitorsJohanna Berg0Zia Weber1Mona Fechler-Bitteti2Andreas C. Hocke3Stefan Hippenstiel4Laura Elomaa5Marie Weinhart6Jens Kurreck7Department of Applied Biochemistry, Technische Universität Berlin, Chair of Applied Biochemistry, 10623 Berlin, GermanyDepartment of Applied Biochemistry, Technische Universität Berlin, Chair of Applied Biochemistry, 10623 Berlin, GermanyDepartment of Applied Biochemistry, Technische Universität Berlin, Chair of Applied Biochemistry, 10623 Berlin, GermanyDepartment of Internal Medicine/Infectious and Respiratory Diseases, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10115 Berlin, GermanyDepartment of Internal Medicine/Infectious and Respiratory Diseases, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10115 Berlin, GermanyDepartment of Organic Chemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, GermanyDepartment of Organic Chemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, GermanyDepartment of Applied Biochemistry, Technische Universität Berlin, Chair of Applied Biochemistry, 10623 Berlin, GermanyInfluenza 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.https://www.mdpi.com/1999-4915/13/8/1590bioprintinghuman lung modelinfluenza A virusLPS stimulation |
| spellingShingle | Johanna Berg Zia Weber Mona Fechler-Bitteti Andreas C. Hocke Stefan Hippenstiel Laura Elomaa Marie Weinhart Jens Kurreck Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors Viruses bioprinting human lung model influenza A virus LPS stimulation |
| 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 | bioprinting human lung model influenza A virus LPS stimulation |
| url | https://www.mdpi.com/1999-4915/13/8/1590 |
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