{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:07:07Z","timestamp":1760148427090,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Bacterial pleural infections are associated with high mortality. Treatment is complicated due to biofilm formation. A common causative pathogen is Staphylococcus aureus (S. aureus). Since it is distinctly human-specific, rodent models do not provide adequate conditions for research. The purpose of this study was to examine the effects of S. aureus infection on human pleural mesothelial cells using a recently established 3D organotypic co-culture model of pleura derived from human specimens. After infection of our model with S. aureus, samples were harvested at defined time points. Histological analysis and immunostaining for tight junction proteins (c-Jun, VE-cadherin, and ZO-1) were performed, demonstrating changes comparable to in vivo empyema. The measurement of secreted cytokine levels (TNF-\u03b1, MCP-1, and IL-1\u03b2) proved host\u2013pathogen interactions in our model. Similarly, mesothelial cells produced VEGF on in vivo levels. These findings were contrasted by vital, unimpaired cells in a sterile control model. We were able to establish a 3D organotypic in vitro co-culture model of human pleura infected with S. aureus resulting in the formation of biofilm, including host\u2013pathogen interactions. This novel model could be a useful microenvironment tool for in vitro studies on biofilm in pleural empyema.<\/jats:p>","DOI":"10.3390\/bioengineering10050537","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T02:02:23Z","timestamp":1682647343000},"page":"537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Organotypic 3D Co-Culture of Human Pleura as a Novel In Vitro Model of Staphylococcus\u00a0aureus Infection and Biofilm Development"],"prefix":"10.3390","volume":"10","author":[{"given":"Olga","family":"Kurow","sequence":"first","affiliation":[{"name":"Department of Orthopedic, Trauma and Plastic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7587-1968","authenticated-orcid":false,"given":"Rima","family":"Nuwayhid","sequence":"additional","affiliation":[{"name":"Department of Orthopedic, Trauma and Plastic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9208-8411","authenticated-orcid":false,"given":"Peggy","family":"Stock","sequence":"additional","affiliation":[{"name":"Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Steinert","sequence":"additional","affiliation":[{"name":"Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Langer","sequence":"additional","affiliation":[{"name":"Department of Orthopedic, Trauma and Plastic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4867-8884","authenticated-orcid":false,"given":"Sebastian","family":"Kr\u00e4mer","sequence":"additional","affiliation":[{"name":"Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella B.","family":"Metelmann","sequence":"additional","affiliation":[{"name":"Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1900542","DOI":"10.1183\/13993003.00542-2019","article-title":"The microbiology of pleural infection in adults: A systematic review","volume":"54","author":"Hassan","year":"2019","journal-title":"Eur. 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