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Initial lesions of PDAC develop within the exocrine pancreas\u2019 functional units, with tumor progression driven by interactions between PDAC and stromal cells. Effective therapies require anatomically and functionally relevant <jats:italic>in vitro<\/jats:italic> human models of the pancreatic cancer microenvironment. We employed tomographic volumetric bioprinting, a novel biofabrication method, to create human fibroblast-laden constructs mimicking the tubuloacinar structures of the exocrine pancreas. Human pancreatic ductal epithelial (HPDE) cells overexpressing the KRAS oncogene (HPDE-KRAS) were seeded in the multiacinar cavity to replicate pathological tissue. HPDE cell growth and organization within the structure were assessed, demonstrating the formation of a thin epithelium covering the acini inner surfaces. Immunofluorescence assays showed significantly higher alpha smooth muscle actin (<jats:italic>\u03b1<\/jats:italic>-SMA) vs. F-actin expression in fibroblasts co-cultured with cancerous versus wild-type HPDE cells. Additionally, <jats:italic>\u03b1<\/jats:italic>-SMA expression increased over time and was higher in fibroblasts closer to HPDE cells. Elevated interleukin (IL)-6 levels were quantified in supernatants from co-cultures of stromal and HPDE-KRAS cells. These findings align with inflamed tumor-associated myofibroblast behavior, serving as relevant biomarkers to monitor early disease progression and target drug efficacy. To our knowledge, this is the first demonstration of a 3D bioprinted model of exocrine pancreas that recapitulates its true 3-dimensional microanatomy and shows tumor triggered inflammation.<\/jats:p>","DOI":"10.1088\/1758-5090\/ad6d8d","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T22:51:50Z","timestamp":1723243910000},"page":"045034","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["3D in vitro modeling of the exocrine pancreatic unit using tomographic volumetric bioprinting"],"prefix":"10.1088","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7633-5478","authenticated-orcid":true,"given":"Viola","family":"Sgarminato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3945-538X","authenticated-orcid":false,"given":"Jorge","family":"Madrid-Wolff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-8519","authenticated-orcid":false,"given":"Antoine","family":"Boniface","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0199-1427","authenticated-orcid":false,"given":"Gianluca","family":"Ciardelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2149-7533","authenticated-orcid":true,"given":"Chiara","family":"Tonda-Turo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-0273","authenticated-orcid":false,"given":"Christophe","family":"Moser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"key":"bfad6d8dbib1","doi-asserted-by":"publisher","first-page":"3234","DOI":"10.3390\/cancers12113234","article-title":"Recent discoveries of diagnostic, prognostic and predictive biomarkers for pancreatic cancer","volume":"12","author":"Khomiak","year":"2020","journal-title":"Cancers"},{"key":"bfad6d8dbib2","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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