{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T12:16:29Z","timestamp":1789215389933,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovative Medicines Initiative 2 Joint Undertaking","award":["821520"],"award-info":[{"award-number":["821520"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program and EFPIA","award":["821520"],"award-info":[{"award-number":["821520"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It is currently impossible to perform an evidence-based risk assessment for medication use during breastfeeding. The ConcePTION project aims to provide information about the use of medicines during lactation. The study aimed to develop and characterize an in vitro model of the blood\u2013milk barrier to determine the extent of the milk transfer of xenobiotics, relying on either on human mammary epithelial cells (hMECs) or immortalized cell lines derived from breast tissue. The hMECs were cultured and characterized for epithelial markers; further, the ability to form an epithelial barrier was investigated. Drug transporter functionality in the cultured hMECs was analyzed with specific probe substrates. The hMECs showed an epithelial morphology and the expression of epithelial markers and tight junctions. They formed a reproducible tight barrier with a transepithelial electrical resistance greater than 400 \u03a9cm2, unlike immortalized cell lines. Different levels of mRNA expression were detected for 81 genes of membrane transporters. Functional assays showed no evidence for the transporter-mediated secretion of medicines across the hMECs. Nevertheless, the hMEC-based in vitro model covered a 50-fold range of permeability values, differentiating between passive transcellular and paracellular-mediated transport. The cultured hMECs proved to be a promising in vitro model for biorelevance; the wide characterization of hMECs makes them useful for studying medicine partitioning in milk.<\/jats:p>","DOI":"10.3390\/ijms252111454","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T03:46:04Z","timestamp":1729827964000},"page":"11454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Development and Characterization of a Human Mammary Epithelial Cell Culture Model for the Blood\u2013Milk Barrier\u2014A Contribution from the ConcePTION Project"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5649-1852","authenticated-orcid":false,"given":"Debora","family":"La Mantia","sequence":"first","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell\u2019Emilia, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5301-6813","authenticated-orcid":false,"given":"Nina","family":"Nauwelaerts","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition Lab, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, O&N II Herestraat 49\u2014Bus 921, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3384-0244","authenticated-orcid":false,"given":"Chiara","family":"Bernardini","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell\u2019Emilia, 40064 Bologna, Italy"},{"name":"Health Sciences and Technologies-Interdepartmental Center for Industrial Research (CIRI-SDV), Alma Mater Studiorum\u2014University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2972-4921","authenticated-orcid":false,"given":"Augusta","family":"Zannoni","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell\u2019Emilia, 40064 Bologna, Italy"},{"name":"Health Sciences and Technologies-Interdepartmental Center for Industrial Research (CIRI-SDV), Alma Mater Studiorum\u2014University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8819-2857","authenticated-orcid":false,"given":"Roberta","family":"Salaroli","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell\u2019Emilia, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Lin","sequence":"additional","affiliation":[{"name":"BioNotus GCV, Galileilaan 15, 2845 Niel, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Huys","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacotherapy, KU Leuven, ON II Herestraat 49\u2014Bus 521, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-7351","authenticated-orcid":false,"given":"Pieter","family":"Annaert","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition Lab, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, O&N II Herestraat 49\u2014Bus 921, 3000 Leuven, Belgium"},{"name":"BioNotus GCV, Galileilaan 15, 2845 Niel, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1310-6202","authenticated-orcid":false,"given":"Monica","family":"Forni","sequence":"additional","affiliation":[{"name":"Health Sciences and Technologies-Interdepartmental Center for Industrial Research (CIRI-SDV), Alma Mater Studiorum\u2014University of Bologna, 40126 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13006-015-0053-6","article-title":"Postpartum Women\u2019s Use of Medicines and Breastfeeding Practices: A Systematic Review","volume":"10","author":"Saha","year":"2015","journal-title":"Int. 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